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Sample records for albicans double infection

  1. Breakthrough Aspergillus fumigatus and Candida albicans double infection during caspofungin treatment

    DEFF Research Database (Denmark)

    Arendrup, Maiken Cavling; Garcia-Effron, Guillermo; Buzina, Walter

    2009-01-01

    Caspofungin is used for the treatment of acute invasive candidiasis and as salvage treatment for invasive aspergillosis. We report characteristics of isolates of Candida albicans and Aspergillus fumigatus detected in a patient with breakthrough infection complicating severe gastrointestinal surgery...... without FSK1 resistance mutations in liver and lung tissues. Breakthrough disseminated aspergillosis and candidiasis developed despite an absence of characteristic FKS1 resistance mutations in the Aspergillus isolates. EUCAST and CLSI methodology did not separate the candin-resistant clinical isolate from...

  2. Candida albicans infection of Caenorhabditis elegans induces antifungal immune defenses.

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    Read Pukkila-Worley

    2011-06-01

    Full Text Available Candida albicans yeast cells are found in the intestine of most humans, yet this opportunist can invade host tissues and cause life-threatening infections in susceptible individuals. To better understand the host factors that underlie susceptibility to candidiasis, we developed a new model to study antifungal innate immunity. We demonstrate that the yeast form of C. albicans establishes an intestinal infection in Caenorhabditis elegans, whereas heat-killed yeast are avirulent. Genome-wide, transcription-profiling analysis of C. elegans infected with C. albicans yeast showed that exposure to C. albicans stimulated a rapid host response involving 313 genes (124 upregulated and 189 downregulated, ~1.6% of the genome many of which encode antimicrobial, secreted or detoxification proteins. Interestingly, the host genes affected by C. albicans exposure overlapped only to a small extent with the distinct transcriptional responses to the pathogenic bacteria Pseudomonas aeruginosa or Staphylococcus aureus, indicating that there is a high degree of immune specificity toward different bacterial species and C. albicans. Furthermore, genes induced by P. aeruginosa and S. aureus were strongly over-represented among the genes downregulated during C. albicans infection, suggesting that in response to fungal pathogens, nematodes selectively repress the transcription of antibacterial immune effectors. A similar phenomenon is well known in the plant immune response, but has not been described previously in metazoans. Finally, 56% of the genes induced by live C. albicans were also upregulated by heat-killed yeast. These data suggest that a large part of the transcriptional response to C. albicans is mediated through "pattern recognition," an ancient immune surveillance mechanism able to detect conserved microbial molecules (so-called pathogen-associated molecular patterns or PAMPs. This study provides new information on the evolution and regulation of the innate

  3. Systemic non-albicans infections presented as meningitis in chronic hepatitis B patient: a case report

    OpenAIRE

    Wen-Jing Lv; Hui Bu; Jun-Ying He; Ran-Ran Sun; Yue-Li Zou

    2014-01-01

    Non-albicans candida meningitis is a relatively rare disease, with nonspecific clinical manifestation, which makes the misdiagnosis occur sometimes, especially in the early stage of the disease. Abuse of broad-spectrum antibiotics, corticosteroids, central vein cannulas, senility, big operation, malignancy, and total parenteral alimentation were all the susceptible factors of non-albicans candida infection. We present a case of this type of non-albicans infection in a 42-year-old woman who wa...

  4. Candida albicans infection in patients with oral squamous cell carcinoma

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    Čanković Miloš

    2010-01-01

    Full Text Available Bacground/Aim. Systemic candidiasis in intensive care units remains an improtant problem due to antifungal resistance. Patients undergoing radiotherapy for head and neck cancer are at increased risk of developing oral candidiasis and they more frequent have prior fungi colonization. Due to identification of specific risk factors predisposing to fungal infection in order to threat such patients the aim of this study was to determine the presence of Candida species in patients with oral squamous cell carcinoma and compare it to the control subjects (patients with benign oral mucosal lesions. Methods. A total number of 30 consecutive oral cancer examined patients were included in this prospective study (24 men and 6 women with a mean age of 61.47 years, range 41-81 years. The control group consisted of 30 consecutive patients with histologically proven benign oral mucosal lesions (16 men and 14 women with a mean age of 54.53 years, range 16- 83 years. The samples for mycological examination were obtained by using sterile cotton swabs from the cancer lesion surface and in the patients of the control group from the benign mucosal lesion surface. Samples were inoculated in Sabouraud' dextrose agar. For identification purposes, Mackenzie germ tube test was performend on all isolates. Results. The prevalence of Candida was significantly higher in oral cancer patients than in control subjects (χ2 = 5.455, p = 0.020. Candida was found on nine of the 30 cancer surfaces; 5 (16.7% were identified as non-albicans Candida and 4 (13.3% as Candida albicans. In the control group, only Candida albicans was isolated from 2 (6.7% patients. In this study, no statistically significant differences in the presence of Candida species was found with respect to gender, age, smoking, alcohol consumption, wearing of dental protheses and the site of cancer lesion. Conclusion. The increased prevalence of yeasts on the surfaces of oral carcinoma indicates a need for their

  5. Baicalin prevents Candida albicans infections via increasing its apoptosis rate

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    Yang, Shulong; Fu, Yingyuan, E-mail: yingyuanfu@126.com; Wu, Xiuzhen; Zhou, Zhixing; Xu, Jing; Zeng, Xiaoping; Kuang, Nanzhen; Zeng, Yurong

    2014-08-15

    Highlights: • Baicalin increases the ratio of the G0/G1 stages and C. albicans apoptosis. • Baicalin decreases the proliferation index of C. albicans. • Baicalin inhibits the biosynthesis of DNA, RNA and protein in C. albicans. • Baicalin depresses Succinate Dehydrogenase and Ca{sup 2+}–Mg{sup 2+} ATPase in C. albicans. • Baicalin increases the endocytic free Ca{sup 2+} concentration in C. albicans. - Abstract: Background: These experiments were employed to explore the mechanisms underlying baicalin action on Candida albicans. Methodology and principal findings: We detected the baicalin inhibition effects on three isotope-labeled precursors of {sup 3}H-UdR, {sup 3}H-TdR and {sup 3}H-leucine incorporation into C. albicans using the isotope incorporation technology. The activities of Succinate Dehydrogenase (SDH), cytochrome oxidase (CCO) and Ca{sup 2+}–Mg{sup 2+} ATPase, cytosolic Ca{sup 2+} concentration, the cell cycle and apoptosis, as well as the ultrastructure of C.albicans were also tested. We found that baicalin inhibited {sup 3}H-UdR, {sup 3}H-TdR and {sup 3}H-leucine incorporation into C.albicans (P < 0.005). The activities of the SDH and Ca{sup 2+}–Mg{sup 2+} ATPase of C.albicans in baicalin groups were lower than those in control group (P < 0.05). Ca{sup 2+} concentrations of C. albicans in baicalin groups were much higher than those in control group (P < 0.05). The ratio of C.albicans at the G0/G1 stage increased in baicalin groups in dose dependent manner (P < 0.01). There were a significant differences in the apoptosis rate of C.albicans between baicalin and control groups (P < 0.01). After 12–48 h incubation with baicalin (1 mg/ml), C. albicans shown to be markedly damaged under transmission electron micrographs. Innovation and significance: Baicalin can increase the apoptosis rate of C. albicans. These effects of Baicalin may involved in its inhibiting the activities of the SDH and Ca{sup 2+}–Mg{sup 2+} ATPase, increasing

  6. Baicalin prevents Candida albicans infections via increasing its apoptosis rate

    International Nuclear Information System (INIS)

    Yang, Shulong; Fu, Yingyuan; Wu, Xiuzhen; Zhou, Zhixing; Xu, Jing; Zeng, Xiaoping; Kuang, Nanzhen; Zeng, Yurong

    2014-01-01

    Highlights: • Baicalin increases the ratio of the G0/G1 stages and C. albicans apoptosis. • Baicalin decreases the proliferation index of C. albicans. • Baicalin inhibits the biosynthesis of DNA, RNA and protein in C. albicans. • Baicalin depresses Succinate Dehydrogenase and Ca 2+ –Mg 2+ ATPase in C. albicans. • Baicalin increases the endocytic free Ca 2+ concentration in C. albicans. - Abstract: Background: These experiments were employed to explore the mechanisms underlying baicalin action on Candida albicans. Methodology and principal findings: We detected the baicalin inhibition effects on three isotope-labeled precursors of 3 H-UdR, 3 H-TdR and 3 H-leucine incorporation into C. albicans using the isotope incorporation technology. The activities of Succinate Dehydrogenase (SDH), cytochrome oxidase (CCO) and Ca 2+ –Mg 2+ ATPase, cytosolic Ca 2+ concentration, the cell cycle and apoptosis, as well as the ultrastructure of C.albicans were also tested. We found that baicalin inhibited 3 H-UdR, 3 H-TdR and 3 H-leucine incorporation into C.albicans (P < 0.005). The activities of the SDH and Ca 2+ –Mg 2+ ATPase of C.albicans in baicalin groups were lower than those in control group (P < 0.05). Ca 2+ concentrations of C. albicans in baicalin groups were much higher than those in control group (P < 0.05). The ratio of C.albicans at the G0/G1 stage increased in baicalin groups in dose dependent manner (P < 0.01). There were a significant differences in the apoptosis rate of C.albicans between baicalin and control groups (P < 0.01). After 12–48 h incubation with baicalin (1 mg/ml), C. albicans shown to be markedly damaged under transmission electron micrographs. Innovation and significance: Baicalin can increase the apoptosis rate of C. albicans. These effects of Baicalin may involved in its inhibiting the activities of the SDH and Ca 2+ –Mg 2+ ATPase, increasing cytosolic Ca 2+ content and damaging the ultrastructure of C. albicans

  7. A Case Report of Penile Infection Caused by Fluconazole- and Terbinafine-Resistant Candida albicans.

    Science.gov (United States)

    Hu, Yongxuan; Hu, Yanqing; Lu, Yan; Huang, Shiyun; Liu, Kangxing; Han, Xue; Mao, Zuhao; Wu, Zhong; Zhou, Xianyi

    2017-04-01

    Candida albicans is the most common pathogen that causes balanoposthitis. It often causes recurrence of symptoms probably due to its antifungal resistance. A significant number of balanitis Candida albicans isolates are resistant to azole and terbinafine antifungal agents in vitro. However, balanoposthitis caused by fluconazole- and terbinafine-resistant Candida albicans has rarely been reported. Here, we describe a case of a recurrent penile infection caused by fluconazole- and terbinafine-resistant Candida albicans, as well as the treatments administered to this patient. The isolate from the patient was tested for drug susceptibility in vitro. It was sensitive to itraconazole, voriconazole, clotrimazole and amphotericin B, but not to terbinafine and fluconazole. Thus, oral itraconazole was administrated to this patient with resistant Candida albicans penile infection. The symptoms were improved, and mycological examination result was negative. Follow-up treatment of this patient for 3 months showed no recurrence.

  8. Comparative transcript profiling of Candida albicans and Candida dubliniensis identifies SFL2, a C. albicans gene required for virulence in a reconstituted epithelial infection model.

    LENUS (Irish Health Repository)

    Spiering, Martin J

    2010-02-01

    Candida albicans and Candida dubliniensis are closely related species displaying differences in virulence and genome content, therefore providing potential opportunities to identify novel C. albicans virulence genes. C. albicans gene arrays were used for comparative analysis of global gene expression in the two species in reconstituted human oral epithelium (RHE). C. albicans (SC5314) showed upregulation of hypha-specific and virulence genes within 30 min postinoculation, coinciding with rapid induction of filamentation and increased RHE damage. C. dubliniensis (CD36) showed no detectable upregulation of hypha-specific genes, grew as yeast, and caused limited RHE damage. Several genes absent or highly divergent in C. dubliniensis were upregulated in C. albicans. One such gene, SFL2 (orf19.3969), encoding a putative heat shock factor, was deleted in C. albicans. DeltaDeltasfl2 cells failed to filament under a range of hypha-inducing conditions and exhibited greatly reduced RHE damage, reversed by reintroduction of SFL2 into the DeltaDeltasfl2 strain. Moreover, SFL2 overexpression in C. albicans triggered hyphal morphogenesis. Although SFL2 deletion had no apparent effect on host survival in the murine model of systemic infection, DeltaDeltasfl2 strain-infected kidney tissues contained only yeast cells. These results suggest a role for SFL2 in morphogenesis and an indirect role in C. albicans pathogenesis in epithelial tissues.

  9. Human vaginal epithelial cells augment autophagy marker genes in response to Candida albicans infection.

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    Shroff, Ankit; Sequeira, Roicy; Reddy, Kudumula Venkata Rami

    2017-04-01

    Autophagy plays an important role in clearance of intracellular pathogens. However, no information is available on its involvement in vaginal infections such as vulvo-vaginal candidiasis (VVC). VVC is intimately associated with the immune status of the human vaginal epithelial cells (VECs). The objective of our study is to decipher if autophagy process is involved during Candida albicans infection of VECs. In this study, C. albicans infection system was established using human VEC line (VK2/E6E7). Infection-induced change in the expression of autophagy markers like LC3 and LAMP-1 were analyzed by RT-PCR, q-PCR, Western blot, immunofluorescence and transmission electron microscopy (TEM) studies were carried out to ascertain the localization of autophagosomes. Multiplex ELISA was carried out to determine the cytokine profiles. Analysis of LC3 and LAMP-1 expression at mRNA and protein levels at different time points revealed up-regulation of these markers 6 hours post C. albicans infection. LC3 and LAMP-1 puncti were observed in infected VECs after 12 hours. TEM studies showed C. albicans entrapped in autophagosomes. Cytokines-TNF-α and IL-1β were up-regulated in culture supernatants of VECs at 12 hours post-infection. The results suggest that C. albicans invasion led to the activation of autophagy as a host defense mechanism of VECs. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. A virtual infection model quantifies innate effector mechanisms and Candida albicans immune escape in human blood.

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    Kerstin Hünniger

    2014-02-01

    Full Text Available Candida albicans bloodstream infection is increasingly frequent and can result in disseminated candidiasis associated with high mortality rates. To analyze the innate immune response against C. albicans, fungal cells were added to human whole-blood samples. After inoculation, C. albicans started to filament and predominantly associate with neutrophils, whereas only a minority of fungal cells became attached to monocytes. While many parameters of host-pathogen interaction were accessible to direct experimental quantification in the whole-blood infection assay, others were not. To overcome these limitations, we generated a virtual infection model that allowed detailed and quantitative predictions on the dynamics of host-pathogen interaction. Experimental time-resolved data were simulated using a state-based modeling approach combined with the Monte Carlo method of simulated annealing to obtain quantitative predictions on a priori unknown transition rates and to identify the main axis of antifungal immunity. Results clearly demonstrated a predominant role of neutrophils, mediated by phagocytosis and intracellular killing as well as the release of antifungal effector molecules upon activation, resulting in extracellular fungicidal activity. Both mechanisms together account for almost [Formula: see text] of C. albicans killing, clearly proving that beside being present in larger numbers than other leukocytes, neutrophils functionally dominate the immune response against C. albicans in human blood. A fraction of C. albicans cells escaped phagocytosis and remained extracellular and viable for up to four hours. This immune escape was independent of filamentation and fungal activity and not linked to exhaustion or inactivation of innate immune cells. The occurrence of C. albicans cells being resistant against phagocytosis may account for the high proportion of dissemination in C. albicans bloodstream infection. Taken together, iterative experiment

  11. Host defence against disseminated and invasive candida albicans infections.

    NARCIS (Netherlands)

    Vonk, A.G.

    2004-01-01

    The yeast Candida albicans is the primary etiologic agent of disseminated and invasive candidiasis. The incidence of disseminated and invasive candidiasis has paralleled the use of modern medical procedures that adversely affect the immune system, and highlights the difficulty of treating

  12. Systemic non-albicans infections presented as meningitis in chronic hepatitis B patient: a case report

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    Wen-Jing Lv

    2014-12-01

    Full Text Available Non-albicans candida meningitis is a relatively rare disease, with nonspecific clinical manifestation, which makes the misdiagnosis occur sometimes, especially in the early stage of the disease. Abuse of broad-spectrum antibiotics, corticosteroids, central vein cannulas, senility, big operation, malignancy, and total parenteral alimentation were all the susceptible factors of non-albicans candida infection. We present a case of this type of non-albicans infection in a 42-year-old woman who was early misdiagnosed as tuberculous meningitis and was treated with antibiotics and antituberculosis agents. The diagnosis of non-albicans infection was confirmed by fungus culture of the cerebrospinal fluid (CSF with a low detectable rate. This case reminds us that the non-albicans candida meningitis had a nonspecific clinical presentations and laboratory data, and was difficult to differentiate from tuberculosis meningitis. Hence, we should highly suspect this disease if central nervous system infections with uncertain pathogens. Test cell counts; protein and fungus culture of CSF should be used to confirm the diagnosis. Once the diagnosis was established, the patients should receive antifungal treatment based on drug sensitivity tests as early as possible.

  13. Effect of Delta-9-tetrahydrocannabinol on mouse resistance to systemic Candida albicans infection.

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    Gideon W Blumstein

    Full Text Available Delta-9-tetrahydrocannabinol (Δ9-THC, the psychoactive component of marijuana, is known to suppress the immune responses to bacterial, viral and protozoan infections, but its effects on fungal infections have not been studied. Therefore, we investigated the effects of chronic Δ9-THC treatment on mouse resistance to systemic Candida albicans (C. albicans infection. To determine the outcome of chronic Δ9-THC treatment on primary, acute systemic candidiasis, c57BL/6 mice were given vehicle or Δ9-THC (16 mg/kg in vehicle on days 1-4, 8-11 and 15-18. On day 19, mice were infected with 5×10(5 C. albicans. We also determined the effect of chronic Δ9-THC (4-64 mg/kg treatment on mice infected with a non-lethal dose of 7.5×10(4 C. albicans on day 2, followed by a higher challenge with 5×10(5 C. albicans on day 19. Mouse resistance to the infection was assessed by survival and tissue fungal load. Serum cytokine levels were determine to evaluate the immune responses. In the acute infection, chronic Δ9-THC treatment had no effect on mouse survival or tissue fungal load when compared to vehicle treated mice. However, Δ9-THC significantly suppressed IL-12p70 and IL-12p40 as well as marginally suppressed IL-17 versus vehicle treated mice. In comparison, when mice were given a secondary yeast infection, Δ9-THC significantly decreased survival, increased tissue fungal burden and suppressed serum IFN-γ and IL-12p40 levels compared to vehicle treated mice. The data showed that chronic Δ9-THC treatment decreased the efficacy of the memory immune response to candida infection, which correlated with a decrease in IFN-γ that was only observed after the secondary candida challenge.

  14. Antifungal activity of caspofungin in experimental infective endocarditis caused by Candida albicans.

    Science.gov (United States)

    Victorio, Gerardo Becerra; Bourdon, Lorena Michele Brennan; Benavides, Leonel García; Huerta-Olvera, Selene G; Plascencia, Arturo; Villanueva, José; Martinez-Lopez, Erika; Hernández-Cañaveral, Iván Isidro

    2017-05-01

    Infective endocarditis is a disease characterised by heart valve lesions, which exhibit extracellular matrix proteins that act as a physical barrier to prevent the passage of antimicrobial agents. The genus Candida has acquired clinical importance given that it is increasingly being isolated from cases of nosocomial infections. To evaluate the activity of caspofungin compared to that of liposomal amphotericin B against Candida albicans in experimental infective endocarditis. Wistar rats underwent surgical intervention and infection with strains of C. albicans to develop infective endocarditis. Three groups were formed: the first group was treated with caspofungin, the second with liposomal amphotericin B, and the third received a placebo. In vitro sensitivity was first determined to further evaluate the effect of these treatments on a rat experimental model of endocarditis by semiquantitative culture of fibrinous vegetations and histological analysis. Our semiquantitative culture of growing vegetation showed massive C. albicans colonisation in rats without treatment, whereas rats treated with caspofungin showed significantly reduced colonisation, which was similar to the results obtained with liposomal amphotericin B. The antifungal activity of caspofungin is similar to that of liposomal amphotericin B in an experimental model of infective endocarditis caused by C. albicans.

  15. Effect of a Lactobacillus Salivarius Probiotic on a Double-Species Streptococcus Mutans and Candida Albicans Caries Biofilm.

    Science.gov (United States)

    Krzyściak, Wirginia; Kościelniak, Dorota; Papież, Monika; Vyhouskaya, Palina; Zagórska-Świeży, Katarzyna; Kołodziej, Iwona; Bystrowska, Beata; Jurczak, Anna

    2017-11-14

    The aim of the study was to evaluate the anti-cariogenic effects of Lactobacillus salivarius by reducing pathogenic species and biofilm mass in a double-species biofilm model. Coexistence of S. mutans with C. albicans can cause dental caries progression or recurrence of the disease in the future. Fifty-nine children with diagnosed early childhood caries (ECC) were recruited onto the study. The condition of the children's dentition was defined according to the World Health Organization guidelines. The participants were divided into children with initial enamel demineralization and children showing dentin damage. The study was performed on the S. mutans and C. albicans clinical strains, isolated from dental plaque of patients with ECC. The effect of a probiotic containing Lactobacillus salivarius on the ability of S. mutans and C. albicans to produce a double-species biofilm was investigated in an in vitro model. The biomass of the formed/non-degraded biofilm was analyzed on the basis of its crystal violet staining. The number of colonies of S. mutans and C. albicans (CFU/mL, colony forming units/mL) forming the biofilm was determined. Microorganism morphology in the biofilm was evaluated using a scanning electron microscope (SEM). In vitro analysis demonstrated that the presence of S. mutans increased the number of C. albicans colonies (CFU/mL); the double-species biofilm mass and hyphal forms produced in it by the yeast. L. salivarius inhibited the cariogenic biofilm formation of C. albicans and S. mutans . Under the influence of the probiotic; the biofilm mass and the number of S. mutans ; C. albicans and S. mutans with C. albicans colonies in the biofilm was decreased. Moreover; it can be noted that after the addition of the probiotic; fungi did not form hyphae or germ tubes of pathogenic potential. These results suggest that L. salivarius can secrete intermediates capable of inhibiting the formation of cariogenic S. mutans and C. albicans biofilm; and may

  16. Effect of a Lactobacillus Salivarius Probiotic on a Double-Species Streptococcus Mutans and Candida Albicans Caries Biofilm

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    Wirginia Krzyściak

    2017-11-01

    Full Text Available The aim of the study was to evaluate the anti-cariogenic effects of Lactobacillus salivarius by reducing pathogenic species and biofilm mass in a double-species biofilm model. Coexistence of S. mutans with C. albicans can cause dental caries progression or recurrence of the disease in the future. Fifty-nine children with diagnosed early childhood caries (ECC were recruited onto the study. The condition of the children’s dentition was defined according to the World Health Organization guidelines. The participants were divided into children with initial enamel demineralization and children showing dentin damage. The study was performed on the S. mutans and C. albicans clinical strains, isolated from dental plaque of patients with ECC. The effect of a probiotic containing Lactobacillus salivarius on the ability of S. mutans and C. albicans to produce a double-species biofilm was investigated in an in vitro model. The biomass of the formed/non-degraded biofilm was analyzed on the basis of its crystal violet staining. The number of colonies of S. mutans and C. albicans (CFU/mL, colony forming units/mL forming the biofilm was determined. Microorganism morphology in the biofilm was evaluated using a scanning electron microscope (SEM. In vitro analysis demonstrated that the presence of S. mutans increased the number of C. albicans colonies (CFU/mL; the double-species biofilm mass and hyphal forms produced in it by the yeast. L. salivarius inhibited the cariogenic biofilm formation of C. albicans and S. mutans. Under the influence of the probiotic; the biofilm mass and the number of S. mutans; C. albicans and S. mutans with C. albicans colonies in the biofilm was decreased. Moreover; it can be noted that after the addition of the probiotic; fungi did not form hyphae or germ tubes of pathogenic potential. These results suggest that L. salivarius can secrete intermediates capable of inhibiting the formation of cariogenic S. mutans and C. albicans biofilm

  17. Pathogenesis of Candida albicans infections in the alternative chorio-allantoic membrane chicken embryo model resembles systemic murine infections.

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    Ilse D Jacobsen

    Full Text Available Alternative models of microbial infections are increasingly used to screen virulence determinants of pathogens. In this study, we investigated the pathogenesis of Candida albicans and C. glabrata infections in chicken embryos infected via the chorio-allantoic membrane (CAM and analyzed the virulence of deletion mutants. The developing immune system of the host significantly influenced susceptibility: With increasing age, embryos became more resistant and mounted a more balanced immune response, characterized by lower induction of proinflammatory cytokines and increased transcription of regulatory cytokines, suggesting that immunopathology contributes to pathogenesis. While many aspects of the chicken embryo response resembled murine infections, we also observed significant differences: In contrast to systemic infections in mice, IL-10 had a beneficial effect in chicken embryos. IL-22 and IL-17A were only upregulated after the peak mortality in the chicken embryo model occurred; thus, the role of the Th17 response in this model remains unclear. Abscess formation occurs frequently in murine models, whereas the avian response was dominated by granuloma formation. Pathogenicity of the majority of 15 tested C. albicans deletion strains was comparable to the virulence in mouse models and reduced virulence was associated with significantly lower transcription of proinflammatory cytokines. However, fungal burden did not correlate with virulence and for few mutants like bcr1Δ and tec1Δ different outcomes in survival compared to murine infections were observed. C. albicans strains locked in the yeast stage disseminated significantly more often from the CAM into the embryo, supporting the hypothesis that the yeast morphology is responsible for dissemination in systemic infections. These data suggest that the pathogenesis of C. albicans infections in the chicken embryo model resembles systemic murine infections but also differs in some aspects. Despite

  18. Technetium-99m labelled fluconazole and antimicrobial peptides for imaging of Candida albicans and Aspergillus fumigatus infections

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    Lupetti, Antonella [Department of Infectious Diseases, Leiden University Medical Center (LUMC), Leiden (Netherlands); Dipartimento di Patologia Sperimentale, Biotecnologie Mediche, Univ. di Pisa (Italy); Welling, Mick M. [Department of Radiology, Division of Nuclear Medicine, LUMC, Leiden (Netherlands); Mazzi, Ulderico [Dipartimento di Scienze Farmaceutiche, Universita degli Studi di Padova (Italy); Nibbering, Peter H. [Department of Infectious Diseases, Leiden University Medical Center (LUMC), Leiden (Netherlands); Pauwels, Ernest K.J. [Department of Radiology, Division of Nuclear Medicine, LUMC, Leiden (Netherlands); Department of Radiology, Leiden University Medical Center (LUMC) (Netherlands)

    2002-05-01

    The aim of this study was to investigate whether technetium-99m labelled fluconazole can distinguish fungal from bacterial infections. Fluconazole was labelled with {sup 99m}Tc and radiochemical analysis showed less than 5% impurities. The labelling solution was injected into animals with experimental infections. For comparison, we used two peptides for infection detection, i.e. UBI 29-41 and hLF 1-11, and human IgG, all labelled with {sup 99m}Tc. Mice were infected with Candida albicans or injected with heat-killed C. albicans or lipopolysaccharides to induce sterile inflammation. Also, mice were infected with Staphylococcus aureus or Klebsiella pneumoniae. Next, accumulation of {sup 99m}Tc-fluconazole and {sup 99m}Tc-labelled peptides/IgG at affected sites was determined scintigraphically. {sup 99m}Tc-fluconazole detected C. albicans infections (T/NT ratio=3.6{+-}0.47) without visualising bacterial infections (T/NT ratio=1.3{+-}0.04) or sterile inflammatory processes (heat-killed C. albicans: T/NT ratio=1.3{+-}0.2; lipopolysaccharide: T/NT ratio=1.4{+-}0.1). C. albicans infections were already seen within the first hour after injection of {sup 99m}Tc-fluconazole (T/NT ratio=3.1{+-}0.2). A good correlation (R{sup 2}=0.864; P<0.05) between T/NT ratios for this tracer and the number of viable C. albicans was found. Although {sup 99m}Tc-UBI 29-41 and {sup 99m}Tc-hLF 1-11 were able to distinguish C. albicans infections from sterile inflammatory processes in mice, these {sup 99m}Tc-labelled peptides did not distinguish these fungal infections from bacterial infections. It is concluded that {sup 99m}Tc-fluconazole distinguishes infections with C. albicans from bacterial infections and sterile inflammations. (orig.)

  19. Suppression of humoral response during the course of Candida albicans infection in mice.

    Science.gov (United States)

    Valdez, J C; Meson, O E; de Valdez, G A; Sirena, A

    1984-10-30

    This paper aims at demonstrating the non-specific immunosuppression as regards thyme-dependent antigens sheep erythrocytes (SRBC) during the course of Candida albicans systemic infection. Three lots of syngeneic/BALB/c mice, 8-12 weeks of age, were used. The first normal lot was inoculated via the intraperitoneal route with a (SRBC) suspension (4 X 10(8) cells ml) in a Hank's balanced saline solution. The primary response of antibodies formed by splenic cells was measured from 4 to 8 days after inoculation using the direct plaque forming cells technique. The second lot was infected by the same route with a suspension of Candida albicans (1 X 10(7) cells). Positive retrocultures from the blood and kidneys of these infected mice were obtained. These yeasts cultivated in a Sabouraud medium were harvested after 20 h at 37 degrees C. Following the same methodology the immune response to SRBC was determined. The serum obtained from infected mice was transferred to a third lot of mice at different intervals during the course of the infection. The immune response to SRBC was done by the direct plaque-forming cells technique. Controls were carried out using normal donors and recipients. A suppression of the immune response was obtained as from the 2nd day of inoculation up to the 28th day. It was not possible to transfer such suppression passively by means of the serum. These results suggest that the systemic infection by Candida albicans induce a non-specific immunosuppression in the organism, already demonstrated in viral infections, bacteria, protozoaria and metazoaria in mammals. In some way, this will contribute to explain the mechanisms of immune response to Candida albicans.

  20. Lactobacillus paracasei modulates the immune system of Galleria mellonella and protects against Candida albicans infection.

    Science.gov (United States)

    Rossoni, Rodnei Dennis; Fuchs, Beth Burgwyn; de Barros, Patrícia Pimentel; Velloso, Marisol Dos Santos; Jorge, Antonio Olavo Cardoso; Junqueira, Juliana Campos; Mylonakis, Eleftherios

    2017-01-01

    Probiotics have been described as a potential strategy to control opportunistic infections due to their ability to stimulate the immune system. Using the non-vertebrate model host Galleria mellonella, we evaluated whether clinical isolates of Lactobacillus spp. are able to provide protection against Candida albicans infection. Among different strains of Lactobacillus paracasei, Lactobacillus rhamnosus and Lactobacillus fermentum, we verified that L. paracasei 28.4 strain had the greatest ability to prolong the survival of larvae infected with a lethal dose of C. albicans. We found that the injection of 107 cells/larvae of L. paracasei into G. mellonella larvae infected by C. albicans increased the survival of these insects compared to the control group (P = 0.0001). After that, we investigated the immune mechanisms involved in the protection against C. albicans infection, evaluating the number of hemocytes and the gene expression of antifungal peptides. We found that L. paracasei increased the hemocyte quantity (2.38 x 106 cells/mL) in relation to the control group (1.29 x 106 cells/mL), indicating that this strain is capable of raising the number of circulating hemocytes into the G. mellonella hemolymph. Further, we found that L. paracasei 28.4 upregulated genes that encode the antifungal peptides galiomicin and gallerymicin. In relation to the control group, L. paracasei 28.4 increased gene expression of galiomicin by 6.67-fold and 17.29-fold for gallerymicin. Finally, we verified that the prophylactic provision of probiotic led to a significant reduction of the number of fungal cells in G. mellonella hemolymph. In conclusion, L. paracasei 28.4 can modulate the immune system of G. mellonella and protect against candidiasis.

  1. Lactobacillus paracasei modulates the immune system of Galleria mellonella and protects against Candida albicans infection

    Science.gov (United States)

    Rossoni, Rodnei Dennis; Fuchs, Beth Burgwyn; de Barros, Patrícia Pimentel; Velloso, Marisol dos Santos; Jorge, Antonio Olavo Cardoso; Junqueira, Juliana Campos; Mylonakis, Eleftherios

    2017-01-01

    Probiotics have been described as a potential strategy to control opportunistic infections due to their ability to stimulate the immune system. Using the non-vertebrate model host Galleria mellonella, we evaluated whether clinical isolates of Lactobacillus spp. are able to provide protection against Candida albicans infection. Among different strains of Lactobacillus paracasei, Lactobacillus rhamnosus and Lactobacillus fermentum, we verified that L. paracasei 28.4 strain had the greatest ability to prolong the survival of larvae infected with a lethal dose of C. albicans. We found that the injection of 107 cells/larvae of L. paracasei into G. mellonella larvae infected by C. albicans increased the survival of these insects compared to the control group (P = 0.0001). After that, we investigated the immune mechanisms involved in the protection against C. albicans infection, evaluating the number of hemocytes and the gene expression of antifungal peptides. We found that L. paracasei increased the hemocyte quantity (2.38 x 106 cells/mL) in relation to the control group (1.29 x 106 cells/mL), indicating that this strain is capable of raising the number of circulating hemocytes into the G. mellonella hemolymph. Further, we found that L. paracasei 28.4 upregulated genes that encode the antifungal peptides galiomicin and gallerymicin. In relation to the control group, L. paracasei 28.4 increased gene expression of galiomicin by 6.67-fold and 17.29-fold for gallerymicin. Finally, we verified that the prophylactic provision of probiotic led to a significant reduction of the number of fungal cells in G. mellonella hemolymph. In conclusion, L. paracasei 28.4 can modulate the immune system of G. mellonella and protect against candidiasis. PMID:28267809

  2. Sequential Dysfunction and Progressive Depletion of Candida albicans-Specific CD4 T Cell Response in HIV-1 Infection

    Science.gov (United States)

    Liu, Fengliang; Fan, Xiuzhen; Auclair, Sarah; Ferguson, Monique; Sun, Jiaren; Soong, Lynn; Hou, Wei; Redfield, Robert R.; Birx, Deborah L.; Ratto-Kim, Silvia; Robb, Merlin L.; Kim, Jerome H.; Michael, Nelson L.; Hu, Haitao

    2016-01-01

    Loss of immune control over opportunistic infections can occur at different stages of HIV-1 (HIV) disease, among which mucosal candidiasis caused by the fungal pathogen Candida albicans (C. albicans) is one of the early and common manifestations in HIV-infected human subjects. The underlying immunological basis is not well defined. We have previously shown that compared to cytomegalovirus (CMV)-specific CD4 cells, C. albicans-specific CD4 T cells are highly permissive to HIV in vitro. Here, based on an antiretroviral treatment (ART) naïve HIV infection cohort (RV21), we investigated longitudinally the impact of HIV on C. albicans- and CMV-specific CD4 T-cell immunity in vivo. We found a sequential dysfunction and preferential depletion for C. albicans-specific CD4 T cell response during progressive HIV infection. Compared to Th1 (IFN-γ, MIP-1β) functional subsets, the Th17 functional subsets (IL-17, IL-22) of C. albicans-specific CD4 T cells were more permissive to HIV in vitro and impaired earlier in HIV-infected subjects. Infection history analysis showed that C. albicans-specific CD4 T cells were more susceptible to HIV in vivo, harboring modestly but significantly higher levels of HIV DNA, than CMV-specific CD4 T cells. Longitudinal analysis of HIV-infected individuals with ongoing CD4 depletion demonstrated that C. albicans-specific CD4 T-cell response was preferentially and progressively depleted. Taken together, these data suggest a potential mechanism for earlier loss of immune control over mucosal candidiasis in HIV-infected patients and provide new insights into pathogen-specific immune failure in AIDS pathogenesis. PMID:27280548

  3. Solitary Candida albicans Infection Causing Fournier Gangrene and Review of Fungal Etiologies.

    Science.gov (United States)

    Perkins, Tiffany A; Bieniek, Jared M; Sumfest, Joel M

    2014-01-01

    Polymicrobial bacterial infections are commonly found in cases of Fournier gangrene (FG), although fungal growth may occur occasionally. Solitary fungal organisms causing FG have rarely been reported. The authors describe a case of an elderly man with a history of diabetes who presented with a necrotizing scrotal and perineal soft tissue infection. He underwent emergent surgical debridement with findings of diffuse urethral stricture disease and urinary extravasation requiring suprapubic tube placement. Candida albicans was found to be the single causative organism on culture, and the patient recovered well following antifungal treatment. Fungal infections should be considered as rare causes of necrotizing fasciitis and antifungal treatment considered in at-risk immunodeficient individuals.

  4. Bilateral endogenous Candida albicans subretinal abscess with suspected mixed bacterial infection

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    Arai Y

    2014-10-01

    Full Text Available Yusuke Arai,1 Yukihiro Sato,1 Atsushi Yoshida,1 Hidetoshi Kawashima,1 Toshikatsu Kaburaki,2 Harumi Gomi3 1Department of Ophthalmology, Jichi Medical University, Tochigi, Japan; 2Department of Ophthalmology, The University of Tokyo, Graduate School of Medicine, Tokyo, Japan; 3Center for Clinical Infectious Diseases, Jichi Medical University, Tochigi, Japan Purpose: Candida albicans subretinal abscess is extremely rare. To our knowledge, only one unilateral case has been reported. Herein, we report one bilateral case. Mixed bacterial infection was also suspected based on broad-range real-time polymerase chain reaction.Methods: A 64-year-old man being treated with oral corticosteroids for interstitial pneumonia visited us for visual loss in the left eye. Best corrected visual acuity (BCVA was 20/20 in the right eye and 8/200 in the left eye. Funduscopy revealed round yellowish-white subretinal lesions with retinal hemorrhage in both eyes.Results: Broad-range polymerase chain reaction of the vitreous fluid from the left eye showed a high copy count of bacterial 16s ribosome RNA. Despite large doses of antibiotics, the abscess expanded and vision decreased to light perception in the left eye. Exenteration of the left eye was performed followed by microscopic examination showing Gram-negative bacilli, and C. albicans was also cultured. Antibiotics and the maximum doses of antifungal drugs were administered. However, the abscess in the right eye expanded, and BCVA decreased to 2/200. Vitrectomy and silicone oil tamponade were performed. Vitreous fluid culture revealed C. albicans. At 16 months follow-up, BCVA was stable at 4/200 with healing of the subretinal abscess under silicone oil.Conclusion: Since C. albicans subretinal abscess is extremely rare and there was a concurrent mixed bacterial infection, diagnostic procedures in our bilateral case were more complicated than usual. C. albicans infection should be included in the differential diagnosis

  5. May one-stage exchange for Candida albicans peri-prosthetic infection be successful?

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    Jenny, J-Y; Goukodadja, O; Boeri, C; Gaudias, J

    2016-02-01

    Fungal infection of a total joint arthroplasty has a low incidence but is generally considered as more difficult to cure than bacterial infection. As for bacterial infection, two-stage exchange is considered as the gold standard of treatment. We report two cases of one-stage total joint exchange for fungal peri-prosthetic infection with Candida albicans, where the responsible pathogens was only identified on intraoperative samples. This situation can be considered as a one-stage exchange for fungal peri-prosthetic infection without preoperative identification of the responsible organism, which is considered as having a poor prognosis. Both cases were free of infection after two years. One-stage revision has several potential advantages over two-stage revision, including shorter hospital stay and rehabilitation, no interim period with significant functional impairment, shorter antibiotic treatment, better functional outcome and probably lower costs. We suggest that one-stage revision for C. albicans peri-prosthetic infection may be successful even without preoperative fungal identification. Level IV-Historical cases. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  6. Dissecting Candida albicans Infection from the Perspective of C. albicans Virulence and Omics Approaches on Host–Pathogen Interaction: A Review

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    Voon Kin Chin

    2016-10-01

    Full Text Available Candida bloodstream infections remain the most frequent life-threatening fungal disease, with Candida albicans accounting for 70% to 80% of the Candida isolates recovered from infected patients. In nature, Candida species are part of the normal commensal flora in mammalian hosts. However, they can transform into pathogens once the host immune system is weakened or breached. More recently, mortality attributed to Candida infections has continued to increase due to both inherent and acquired drug resistance in Candida, the inefficacy of the available antifungal drugs, tedious diagnostic procedures, and a rising number of immunocompromised patients. Adoption of animal models, viz. minihosts, mice, and zebrafish, has brought us closer to unraveling the pathogenesis and complexity of Candida infection in human hosts, leading towards the discovery of biomarkers and identification of potential therapeutic agents. In addition, the advancement of omics technologies offers a holistic view of the Candida-host interaction in a non-targeted and non-biased manner. Hence, in this review, we seek to summarize past and present milestone findings on C. albicans virulence, adoption of animal models in the study of C. albicans infection, and the application of omics technologies in the study of Candida–host interaction. A profound understanding of the interaction between host defense and pathogenesis is imperative for better design of novel immunotherapeutic strategies in future.

  7. BAY 41-2272 activates host defence against local and disseminated Candida albicans infections

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    Paulo Vítor Soeiro-Pereira

    2015-02-01

    Full Text Available In our previous study, we have found that 5-cyclopropyl-2-[1-(2-fluoro-benzyl-1H-pyrazolo[3,4-b]pyridine-3-yl]-pyrimidin-4-ylamine (BAY 41-2272, a guanylate cyclase agonist, activates human monocytes and the THP-1 cell line to produce the superoxide anion, increasing in vitro microbicidal activity, suggesting that this drug can be used to modulate immune functioning in primary immunodeficiency patients. In the present work, we investigated the potential of the in vivo administration of BAY 41-2272 for the treatment of Candida albicans and Staphylococcus aureus infections introduced via intraperitoneal and subcutaneous inoculation. We found that intraperitoneal treatment with BAY 41-2272 markedly increased macrophage-dependent cell influx to the peritoneum in addition to macrophage functions, such as spreading, zymosan particle phagocytosis and nitric oxide and phorbol myristate acetate-stimulated hydrogen peroxide production. Treatment with BAY 41-2272 was highly effective in reducing the death rate due to intraperitoneal inoculation of C. albicans, but not S. aureus. However, we found that in vitro stimulation of peritoneal macrophages with BAY 41-2272 markedly increased microbicidal activities against both pathogens. Our results show that the prevention of death by the treatment of C. albicans-infected mice with BAY 41-2272 might occur primarily by the modulation of the host immune response through macrophage activation.

  8. Immunomodulatory and protective effect of probiotic Lactobacillus casei against Candida albicans infection in malnourished mice.

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    Villena, Julio; Salva, Susana; Agüero, Graciela; Alvarez, Susana

    2011-06-01

    The effect of Lactobacillus casei CRL 431 (Lc), when administered as a supplement to a repletion diet, on the resistance of malnourished mice to Candida albicans infection was studied. Weaned mice were malnourished by being given a protein-free diet (PFD) for 21 days. The malnourished mice were then fed a balanced conventional diet (BCD) for 7 days or BCD for 7 days with supplemental Lc on days 6 and 7 (BCD+Lc). Malnourished (MNC) and well-nourished (WNC) mice were used as controls. At the end of the treatments the mice were infected intraperitoneally with C. albicans. Animals that had received probiotics had improved survival and resistance against this infection compared to those in the BCD and MNC groups. The number and fungicidal activity of phagocytes, and the concentrations of tumor necrosis factor-α, interferon-γ and interleukin-6 (IL-6), increased in blood and infected tissues in all experimental groups, but MNC mice showed lower concentrations than those in the WNC group. BCD and BCD+Lc mice showed higher concentrations of these variables than those in the MNC group, but only the BCD+Lc group presented values similar to the WNC mice. Malnutrition also impaired the production of IL-17 and IL-10 in response to infection. Both repletion treatments normalized IL-17 concentrations, but IL-10 in the BCD+Lc group was significantly higher than in WNC mice. The addition of L. casei to the repletion diet normalized the immune response against C. albicans, allowing efficient recruitment and activation of phagocytes, as well as effective release of pro-inflammatory cytokines. In addition, probiotic treatment induced an increase in IL-10 concentrations, which would have helped to prevent damage caused by the inflammatory response. © 2011 The Societies and Blackwell Publishing Asia Pty Ltd.

  9. Immune response in mice infected with Candida albicans in the mycelial form.

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    Bibas Bonet de Jorrat, M E; de Valdez, G A; de Petrino, S F; Sirena, A; Perdigón, G

    1989-05-01

    The effect of the infection with the mycelial form of a Candida albicans strain (Mycology Dept.) upon the immune system in mice was studied. BALB/c mice were infected intraperitoneally in a single dose of a 3 x 10(6), 6 x 10(6) and 12 x 10(6) cell suspension of the strain. Macrophages's activity was studied the days 7, 14, 21, 28, 35, and 42 after inoculation, by the following assays: phagocytosis in vitro, mononucleated phagocytic system by the colloidal carbon clearance technique, the lymphocyte's activity by the direct plaque forming cells technique (PFC) and delayed hypersensitivity (DTH). Infection with the mycelial form did not affect the peritoneal macrophage's phagocytic ability, neither modified the delayed hypersensitivity to sheep red blood cells (SRBC). However, a slight and transient depression of the lymphocyte stimulation was found. Suppression of PFC to SRBC was high when a 12 x 10(6) cell suspension was used in contrast to the infection with blastospores. These results suggest that systemic infection by Candida albicans in its mycelial form do not induce a non specific immunosuppression.

  10. Effect of cyclophosphamide on the course of Candida albicans infection in normal and vaccinated mice

    International Nuclear Information System (INIS)

    Japoni, A.; Alborzi, A.; Farshad, S.; Hayati, M.; Dehyadegari, Mohammad A.; Mehrabani, D.

    2006-01-01

    To evaluate the immunomodulating effect of cyclophosphamide (Cy) on the course of Candida albicans (C. albicans). We performed this study in the Shiraz Medical School, Shiraz, Iran during April to November 2003. Five groups of 10 mice (vaccinated group) were immunized by 5 equal injections of 2x105, 2.5x105 and 3x105 of the organism intraperitoneally. Then, the group received Cy on day zero and was challenged with lethal doses of C. albicans (7.74x105 colony forming unit) on days zero, one, 3, 6 and 12 post-Cy injection. Another 5 equal groups of 10 mice (non-vaccinated group) received Cy on day zero and similar to vaccinated ones were challenged with lethal doses of the organism too. The control groups received just Cy on day zero and were sacrificed on days zero, one, 3, 6 and 12 days post-Cy injection. We performed the hemogram and the spleen and studied the renal tissues microscopically and macroscopically. In vaccinated group, we observed an increase in survival time and in spleen and renal weights were visible while in non-vaccinated ones, a significant decrease was also observed on days one and 3 and an increased on days 6 and 12 post-Cy injection. We observed atrophy and necrosis in the spleen while inflammation and necrosis were also observed in the kidneys on days one and 3. We noticed a significant hyperplasia in the white pulp on days 6 and 12 post-Cy injection. We conclude that hyperplasia in the white pulp of spleen and the increase in peripheral polymorphonuclears due to selective effects of Cy could effectively protect the animal against C. albicans infection. (author)

  11. Dynamic, morphotype-specific Candida albicans beta-glucan exposure during infection and drug treatment.

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    Robert T Wheeler

    2008-12-01

    Full Text Available Candida albicans, a clinically important dimorphic fungal pathogen that can evade immune attack by masking its cell wall beta-glucan from immune recognition, mutes protective host responses mediated by the Dectin-1 beta-glucan receptor on innate immune cells. Although the ability of C. albicans to switch between a yeast- or hyphal-form is a key virulence determinant, the role of each morphotype in beta-glucan masking during infection and treatment has not been addressed. Here, we show that during infection of mice, the C. albicans beta-glucan is masked initially but becomes exposed later in several organs. At all measured stages of infection, there is no difference in beta-glucan exposure between yeast-form and hyphal cells. We have previously shown that sub-inhibitory doses of the anti-fungal drug caspofungin can expose beta-glucan in vitro, suggesting that the drug may enhance immune activity during therapy. This report shows that caspofungin also mediates beta-glucan unmasking in vivo. Surprisingly, caspofungin preferentially unmasks filamentous cells, as opposed to yeast form cells, both in vivo and in vitro. The fungicidal activity of caspofungin in vitro is also filament-biased, as corroborated using yeast-locked and hyphal-locked mutants. The uncloaking of filaments is not a general effect of anti-fungal drugs, as another anti-fungal agent does not have this effect. These results highlight the advantage of studying host-pathogen interaction in vivo and suggest new avenues for drug development.

  12. Antibodies against glucan, chitin, and Saccharomyces cerevisiae mannan as new biomarkers of Candida albicans infection that complement tests based on C. albicans mannan.

    Science.gov (United States)

    Sendid, B; Dotan, N; Nseir, S; Savaux, C; Vandewalle, P; Standaert, A; Zerimech, F; Guery, B P; Dukler, A; Colombel, J F; Poulain, D

    2008-12-01

    Antibodies against Saccharomyces cerevisiae mannan (ASCA) and antibodies against synthetic disaccharide fragments of glucans (ALCA) and chitin (ACCA) are biomarkers of Crohn's disease (CD). We previously showed that Candida albicans infection generates ASCA. Here, we explored ALCA and ACCA as possible biomarkers of invasive C. albicans infection (ICI). ASCA, ALCA, ACCA, and Candida mannan antigen and antibody detection tests were performed on 69 sera obtained sequentially from 18 patients with ICIs proven by blood culture, 59 sera from CD patients, 47 sera from hospitalized subjects colonized by Candida species (CZ), and 131 sera from healthy controls (HC). ASCA, ALCA, and ACCA levels in CD and ICI patients were significantly different from those in CZ and HC subjects (PACCA, and Platelia Candida tests, 100% of ICIs were detected, with the kinetics of the antibody response depending on the patient during the time course of infection. A large number of sera presented with more than three positive tests. This is the first evidence that the detection of antibodies against chitin and glucans has diagnostic value in fungal infections and that these tests can complement more specific tests. Future trials are necessary to assess the value of these tests in multiparametric analysis, as well as their pathophysiological relevance.

  13. Examining the virulence of Candida albicans transcription factor mutants using Galleria mellonella and mouse infection models

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    Sara eAmorim-Vaz

    2015-05-01

    Full Text Available The aim of the present study was to identify C. albicans transcription factors (TF involved in virulence. Although mice are considered the gold-standard model to study fungal virulence, mini-host infection models have been increasingly used. Here, barcoded TF mutants were first screened in mice by pools of strains and fungal burdens quantified in kidneys. Mutants of unannotated genes which generated a kidney fungal burden significantly different from that of wild-type were selected and individually examined in G. mellonella. In addition, mutants that could not be detected in mice were also tested in G. mellonella. Only 25 % of these mutants displayed matching phenotypes in both hosts, highlighting a significant discrepancy between the two models. To address the basis of this difference (pool or host effects, a set of 19 mutants tested in G. mellonella were also injected individually into mice. Matching fungal burden phenotypes were observed in 50 % of the cases, highlighting the bias due to host effects. In contrast, 33.4 % concordance was observed between pool and single strain infections in mice, thereby highlighting the bias introduced by the pool effect. After filtering the results obtained from the two infection models, mutants for MBF1 and ZCF6 were selected. Independent marker-free mutants were subsequently tested in both hosts to validate previous results. The MBF1 mutant showed impaired infection in both models, while the ZCF6 mutant was only significant in mice infections. The two mutants showed no obvious in vitro phenotypes compared with the wild-type, indicating that these genes might be specifically involved in in vivo adaptation.

  14. Characteristics of experimental Candida albicans infection of the central nervous system in rabbits.

    Science.gov (United States)

    Jafari, H S; Sáez-Llorens, X; Grimprel, E; Argyle, J C; Olsen, K D; McCracken, G H

    1991-08-01

    Different concentrations (10(7), 10(5), 10(3) cfu/ml) of Candida albicans were injected intracisternally in rabbits. The highest inoculum was fatal within 14 h in all animals. In recipients of 10(5) and 10(3) cfu/ml inocula, the mean +/- SD peak cerebrospinal fluid (CSF) tumor necrosis factor-alpha (TNF alpha) concentrations were 1.6 +/- 2.42 and 0.3 +/- 0.59 ng/ml, respectively, at 6 h; the mean +/- SD CSF leukocyte and protein concentrations were 6291 +/- 6515 and 453 +/- 674 cells/mm3 (at 24 h) and 118 +/- 90 and 109 +/- 122 mg/dl (at 12 and 24 h), respectively. At 6-10 days after inoculation, a second peak of TNF alpha activity was accompanied by increased CSF inflammation. Mortality in the 10(5) and 10(3) cfu/ml inoculum groups was 56% and 22%, respectively. Fatal infection was associated with higher second CSF peak TNF alpha and leukocyte concentrations and a larger proportion of culture-positive CSF samples. Histopathology revealed hyphal invasion, vasculitis, abscesses, and acute and chronic inflammatory infiltration of meninges and brain parenchyma. This model can be useful for evaluation of the pathogenesis and therapy of central nervous system fungal infections.

  15. The Hyr1 protein from the fungus Candida albicans is a cross kingdom immunotherapeutic target for Acinetobacter bacterial infection.

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    Priya Uppuluri

    2018-05-01

    Full Text Available Different pathogens share similar medical settings and rely on similar virulence strategies to cause infections. We have previously applied 3-D computational modeling and bioinformatics to discover novel antigens that target more than one human pathogen. Active and passive immunization with the recombinant N-terminus of Candida albicans Hyr1 (rHyr1p-N protect mice against lethal candidemia. Here we determine that Hyr1p shares homology with cell surface proteins of the multidrug resistant Gram negative bacterium, Acinetobacter baumannii including hemagglutinin (FhaB and outer membrane protein A (OmpA. The A. baumannii OmpA binds to C. albicans Hyr1p, leading to a mixed species biofilm. Deletion of HYR1, or blocking of Hyr1p using polyclonal antibodies, significantly reduce A. baumannii binding to C. albicans hyphae. Furthermore, active vaccination with rHyr1p-N or passive immunization with polyclonal antibodies raised against specific peptide motifs of rHyr1p-N markedly improve survival of diabetic or neutropenic mice infected with A. baumannii bacteremia or pneumonia. Antibody raised against one particular peptide of the rHyr1p-N sequence (peptide 5 confers majority of the protection through blocking A. baumannii invasion of host cells and inducing death of the bacterium by a putative iron starvation mechanism. Anti-Hyr1 peptide 5 antibodies also mitigate A. baumannii /C. albicans mixed biofilm formation in vitro. Consistent with our bioinformatic analysis and structural modeling of Hyr1p, anti-Hyr1p peptide 5 antibodies bound to A. baumannii FhaB, OmpA, and an outer membrane siderophore binding protein. Our studies highlight the concept of cross-kingdom vaccine protection against high priority human pathogens such as A. baumannii and C. albicans that share similar ecological niches in immunocompromised patients.

  16. Bst1 is required for Candida albicans infecting host via facilitating cell wall anchorage of Glycosylphosphatidyl inositol anchored proteins

    Science.gov (United States)

    Liu, Wei; Zou, Zui; Huang, Xin; Shen, Hui; He, Li Juan; Chen, Si Min; Li, Li Ping; Yan, Lan; Zhang, Shi Qun; Zhang, Jun Dong; Xu, Zheng; Xu, Guo Tong; An, Mao Mao; Jiang, Yuan Ying

    2016-01-01

    Glycosylphosphatidyl inositol anchored proteins (GPI-APs) on fungal cell wall are essential for invasive infections. While the function of inositol deacylation of GPI-APs in mammalian cells has been previously characterized the impact of inositol deacylation in fungi and implications to host infection remains largely unexplored. Herein we describe our identification of BST1, an inositol deacylase of GPI-Aps in Candida albicans, was critical for GPI-APs cell wall attachment and host infection. BST1-deficient C. albicans (bst1Δ/Δ) was associated with severely impaired cell wall anchorage of GPI-APs and subsequen unmasked β-(1,3)-glucan. Consistent with the aberrant cell wall structures, bst1Δ/Δ strain did not display an invasive ability and could be recognized more efficiently by host immune systems. Moreover, BST1 null mutants or those expressing Bst1 variants did not display inositol deacylation activity and exhibited severely attenuated virulence and reduced organic colonization in a murine systemic candidiasis model. Thus, Bst1 can facilitate cell wall anchorage of GPI-APs in C. albicans by inositol deacylation, and is critical for host invasion and immune escape. PMID:27708385

  17. Epithelial invasion outcompetes hypha development during Candida albicans infection as revealed by an image-based systems biology approach.

    Science.gov (United States)

    Mech, Franziska; Wilson, Duncan; Lehnert, Teresa; Hube, Bernhard; Thilo Figge, Marc

    2014-02-01

    Candida albicans is the most common opportunistic fungal pathogen of the human mucosal flora, frequently causing infections. The fungus is responsible for invasive infections in immunocompromised patients that can lead to sepsis. The yeast to hypha transition and invasion of host-tissue represent major determinants in the switch from benign colonizer to invasive pathogen. A comprehensive understanding of the infection process requires analyses at the quantitative level. Utilizing fluorescence microscopy with differential staining, we obtained images of C. albicans undergoing epithelial invasion during a time course of 6 h. An image-based systems biology approach, combining image analysis and mathematical modeling, was applied to quantify the kinetics of hyphae development, hyphal elongation, and epithelial invasion. The automated image analysis facilitates high-throughput screening and provided quantities that allow for the time-resolved characterization of the morphological and invasive state of fungal cells. The interpretation of these data was supported by two mathematical models, a kinetic growth model and a kinetic transition model, that were developed using differential equations. The kinetic growth model describes the increase in hyphal length and revealed that hyphae undergo mass invasion of epithelial cells following primary hypha formation. We also provide evidence that epithelial cells stimulate the production of secondary hyphae by C. albicans. Based on the kinetic transition model, the route of invasion was quantified in the state space of non-invasive and invasive fungal cells depending on their number of hyphae. This analysis revealed that the initiation of hyphae formation represents an ultimate commitment to invasive growth and suggests that in vivo, the yeast to hypha transition must be under exquisitely tight negative regulation to avoid the transition from commensal to pathogen invading the epithelium. © 2013 International Society for

  18. Radiotherapy Reduced Salivary Flow Rate and Might Induced C. albicans Infection

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    Nadia Surjadi

    2013-07-01

    Full Text Available Radiotherapy has impact in oral health especially on the secretion capacity of the salivary glands. Another impact is the increase of Candida albicans colony. Objectives: To evaluate salivary flow in relation with Candida albicans colony in head and neck cancer patients during and after radiotherapy. Methods: Twenty-four head and neck cancer patients in Dharmais Cancer Hospital, Jakarta who were undergoing radiotherapy or had undergone radiotherapy and 24 match healthy volunteers were included in the study. Clinical observation carried out by collecting unstimulated salivary flow rate and followed by culture of Candida in Saboraud agar medium. Data were analyzed statistically by Chi-square. Results: Nasopharynx cancer was the most frequent type of head and neck cancers (87.5% followed by tongue cancer (12.5% and and found in 41-50 years old patients and 51-60 years old patients respectively, with male predilection compare to female (17:7. Approxiamtely 87.5% of subjects showed decreased salivary flow rate (1.01-1.50mL/10min during and after radiotherapy. However, 91.7% of cancer patients had increased C.albicans colony during and after radiotherapy compared to control (p=0.00. Conclusion: This study showed that radiotherapy induced hyposalivation and might increase the C.albicans colony.  

  19. Study of the prevalence and association of ocular chlamydial conjunctivitis in women with genital infection by Chlamydia trachomatis, Mycoplasma genitalium and Candida albicans attending outpatient clinic.

    Science.gov (United States)

    Khattab, Rania Abdelmonem; Abdelfattah, Maha Mohssen

    2016-01-01

    To determine the association between chlamydial conjunctivitis and genital infection by Chlamydia trachomatis, Mycoplasma genitalium and Candida albicans, in addition to the possible relationship between cultured bacterial pathogens and oculogenital chlamydial infection. This study was performed on 100 (50 symptomatic and 50 asymptomatic) women attending the Gynecological and Obstetric outpatient clinic of Alzahra hospital, Alazhar University. Simultaneously a conjunctival swab was taken from these patients. Polymerase chain reaction (PCR) was done on DNA extracted from both vaginal and conjunctival swab samples. Culture for both vaginal and conjunctival swabs was also done. Candida albicans was the predominant organism isolated by culture in 20% and 40% of conjunctival and vaginal swabs respectively. By the PCR method, ocular Chlamydia trachomatis was present in 60% of symptomatic women, while genital Chlamydia trachomatis infection was present in 30% of symptomatic women. The results of this method also indicated that 25/50 (50%) vaginal swabs were positive with PCR for Candida albicans versus 15/50 (30%) were PCR positive in conjunctival swab. Mycoplasma genitalium was present in only 10% of vaginal swabs. Concomitant oculogenital PCR positive results for Chlamydia trachomatis and Candida albicans were 30% and 28% respectively. Ocular Chlamydia trachomatis was associated with genital Chlamydia trachomatis in a high percentage of women followed by Candida albicans. Cultured bacterial organisms do not play a role in enhancement of Chlamydia trachomatis infection.

  20. Characteristics of DTH suppressor cells in mice infected with Candida albicans.

    Science.gov (United States)

    Valdez, J C; Mesón, O E; Sirena, A; de Alderete, N G

    1987-05-01

    Inoculation of 10(8) C. albicans intraperitoneally into Balb/c mice at given dosage was reported to induce suppression of antigen-specific delayed-type hypersensitivity. Adoptive transfer of spleen cells into normal syngeneic mice pre-treated with Cyclophosphamide confirmed the existence of suppressor cells in mice. Such cells were sensitive to treatment with anti-theta serum and complement, non-adherent to Sephadex G-10. A pretreatment of the mice with Cyclophosphamide eliminated DTH suppression. Treatment with antimacrophage agents via intraperitoneal abrogated suppression only if being effected before inoculation of alive 10(8) Candida albicans. It is concluded that the spleen suppressor cell is a T-lymphocyte whose precursor is Cyclophosphamide-sensitive, requiring the macrophage to be induced.

  1. Biodistribution of 99mTc-ketoconazole in infection initiated by candida albicans, staphylococcus aureus and escherichia coli

    International Nuclear Information System (INIS)

    Rizky Juwita Sugiharti; Iim Halimah; Isa Mahendra; Maula Eka Sriyani

    2016-01-01

    Infectious diseases remain a major health problem and cause of death worldwide, particularly in developing countries. Nuclear medicine imaging, with better sensitivity, offers an attractive option for diagnosis of infections. 99m Tc-ketoconazole was radiolabeled antibiotic which synthesized by labeling ketoconazole with radionuclide technetium-99m. This radiopharmaceutical is expected to be applied for detection of infection in nuclear medicine therefore 99m Tc-ketoconazole must be selectively concentrated in infection sites. Hence, evaluations of 99m Tc-ketoconazole to detect and locate infection caused by some microorganisms in mice have been conducted. The biodistribution study showed accumulation of 99m Tc ketoconazole in infected thigh at 1 hour p.i with target/non target ratio (T/NT) 3.04 for Candida albicans, 1.93 for Staphylococcus aureus and 2.81 for Escherichia coli. This study showed that 99m Tc-ketoconazole is a promising radiopharmaceutical to detect infection rapidly with high sensitivity. (author)

  2. Oropharyngeal Candidiasis in HIV Infection: Analysis of Impaired Mucosal Immune Response to Candida albicans in Mice Expressing the HIV-1 Transgene

    Directory of Open Access Journals (Sweden)

    Louis de Repentigny

    2015-06-01

    Full Text Available IL-17-producing Th17 cells are of critical importance in host defense against oropharyngeal candidiasis (OPC. Speculation about defective Th17 responses to oral C. albicans infection in the context of HIV infection prompted an investigation of innate and adaptive immune responses to Candida albicans in transgenic mice expressing the genome of HIV-1 in immune cells and displaying an AIDS-like disease. Defective IL-17 and IL-22-dependent mucosal responses to C. albicans were found to determine susceptibility to OPC in these transgenic mice. Innate phagocytes were quantitatively and functionally intact, and individually dispensable for control of OPC and to prevent systemic dissemination of Candida to deep organs. CD8+ T-cells recruited to the oral mucosa of the transgenic mice limited the proliferation of C. albicans in these conditions of CD4+ T-cell deficiency. Therefore, the immunopathogenesis of OPC in the context of HIV infection involves defective T-cell-mediated immunity, failure of crosstalk with innate mucosal immune effector mechanisms, and compensatory cell responses, which limit Candida infection to the oral mucosa and prevent systemic dissemination.

  3. Pathological analysis of the Candida albicans-infected tongue tissues of a murine oral candidiasis model in the early infection stage.

    Science.gov (United States)

    Okada, Masashi; Hisajima, Tatsuya; Ishibashi, Hiroko; Miyasaka, Takahiro; Abe, Shigeru; Satoh, Tazuko

    2013-04-01

    The early pathological process of Candida infection and immunological responses in tongues of the mice with experimental oral candidiasis was analysed. CD-1 mice, pretreated by prednisolone were orally inoculated with Candida albicans. Symptoms were monitored by measuring the area of white tongue coating and number of viable Candida cells in oral cavity. The histopathological analysis was carried by PAS-stain and immunofluorescent staining. IL-4, IL-12p70, IFN-γ, TNF-α in recovered from the homogenates of the tongues were measured by ELISA. The fungus invaded the tongue surface of the mice and white patches developed within 24h after inoculation. Histopathological examination indicated the presence of local acute inflammation in superficial tissues of tongues covered by mycelium of C. albicans. Pathological exacerbation was observed from 24 to 48 h after the inoculation and from then the symptoms of oral candidiasis appeared to move into the recovery phase. Inflammatory cells mainly consisting of neutrophils was accumulated and located under the lesions covered by Candida-hyphae. An increase in IL-12p70 and IFN-γ in tongue homogenates was observed at 48 h after inoculation. The worst condition in the pathological process in experimental oral candidiasis was found 48 h after C. albicans inoculation. When the surface of the Candida-inoculated tongues was covered with Candida-hyphae, a dense accumulation of neutrophils was observed under the lesions and homogenates of the tongues contained increased levels of IL-12p70 and IFN-γ. These suggested that local pathological condition of Candida-infected tongues may be affected by neutrophils accumulation and increased levels of some cytokines. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Oral-resident natural Th17 cells and γδ T cells control opportunistic Candida albicans infections.

    Science.gov (United States)

    Conti, Heather R; Peterson, Alanna C; Brane, Lucas; Huppler, Anna R; Hernández-Santos, Nydiaris; Whibley, Natasha; Garg, Abhishek V; Simpson-Abelson, Michelle R; Gibson, Gregory A; Mamo, Anna J; Osborne, Lisa C; Bishu, Shrinivas; Ghilardi, Nico; Siebenlist, Ulrich; Watkins, Simon C; Artis, David; McGeachy, Mandy J; Gaffen, Sarah L

    2014-09-22

    Oropharyngeal candidiasis (OPC) is an opportunistic fungal infection caused by Candida albicans. OPC is frequent in HIV/AIDS, implicating adaptive immunity. Mice are naive to Candida, yet IL-17 is induced within 24 h of infection, and susceptibility is strongly dependent on IL-17R signaling. We sought to identify the source of IL-17 during the early innate response to candidiasis. We show that innate responses to Candida require an intact TCR, as SCID, IL-7Rα(-/-), and Rag1(-/-) mice were susceptible to OPC, and blockade of TCR signaling by cyclosporine induced susceptibility. Using fate-tracking IL-17 reporter mice, we found that IL-17 is produced within 1-2 d by tongue-resident populations of γδ T cells and CD3(+)CD4(+)CD44(hi)TCRβ(+)CCR6(+) natural Th17 (nTh17) cells, but not by TCR-deficient innate lymphoid cells (ILCs) or NK cells. These cells function redundantly, as TCR-β(-/-) and TCR-δ(-/-) mice were both resistant to OPC. Whereas γδ T cells were previously shown to produce IL-17 during dermal candidiasis and are known to mediate host defense at mucosal surfaces, nTh17 cells are poorly understood. The oral nTh17 population expanded rapidly after OPC, exhibited high TCR-β clonal diversity, and was absent in Rag1(-/-), IL-7Rα(-/-), and germ-free mice. These findings indicate that nTh17 and γδ T cells, but not ILCs, are key mucosal sentinels that control oral pathogens. © 2014 Conti et al.

  5. Induction of Severe Chronic Hyperplastic Candidiasis in Rat by Opportunistic Infection of C. albicans through Combination of Diabetes and Intermittent Prednisolone Administration.

    Science.gov (United States)

    Terayama, Yui; Matsuura, Tetsuro; Ozaki, Kiyokazu

    2017-08-01

    Chronic hyperplastic candidiasis progresses from squamous cell hyperplasia to squamous cell carcinoma (SCC); however, the oncogenic mechanism remains unclear. In the present study, we attempted to induce opportunistic Candida albicans infection and establish chronic hyperplastic candidiasis in rats by combining diabetic condition and prednisolone administration, followed by analysis of the inflammatory cells involved in the disease progression. Female Wistar Bunn/Kobori (WBN/Kob) rats were divided into 3 groups: alloxan-induced diabetic rats (A group) along with diabetic (AP group) and nondiabetic (P group) rats intermittently treated with prednisolone. Animals were euthanized at 42 weeks of age. Squamous cell hyperplasia following C. albicans infection in the forestomach was observed in almost all AP and A group rats. The lesions in the AP group were significantly more severe than those in the A group. In addition, SCC was detected in 1 AP group animal. Cluster of differentiation (CD)4-positive T cell and CD68-positive macrophage infiltration in the AP group was significantly stronger than that in the A group. These findings suggest that the combination of diabetes and intermittent prednisolone administration could induce chronic hyperplastic candidiasis without direct C. albicans inoculation and that CD4-positive T cells and CD68-positive macrophages may be highly involved in the pathogenesis of these hyperplastic lesions.

  6. Serial passaging of Candida albicans in systemic murine infection suggests that the wild type strain SC5314 is well adapted to the murine kidney.

    Directory of Open Access Journals (Sweden)

    Anja Lüttich

    Full Text Available The opportunistic fungal pathogen Candida albicans has a remarkable ability to adapt to unfavorable environments by different mechanisms, including microevolution. For example, a previous study has shown that passaging through the murine spleen can cause new phenotypic characteristics. Since the murine kidney is the main target organ in murine Candida sepsis and infection of the spleen differs from the kidney in several aspects, we tested whether C. albicans SC5314 could evolve to further adapt to infection and persistence within the kidney. Therefore, we performed a long-term serial passage experiment through the murine kidney of using a low infectious dose. We found that the overall virulence of the commonly used wild type strain SC5314 did not change after eight passages and that the isolated pools showed only very moderate changes of phenotypic traits on the population level. Nevertheless, the last passage showed a higher phenotypic variability and a few individual strains exhibited phenotypic alterations suggesting that microevolution has occurred. However, the majority of the tested single strains were phenotypically indistinguishable from SC5314. Thus, our findings indicate that characteristics of SC5314 which are important to establish and maintain kidney infection over a prolonged time are already well developed.

  7. Successful treatment of an acute infective endocarditis secondary to fish bone penetrating into left atrium caused by Granulicatella adiacens and Candida albicans: A case report.

    Science.gov (United States)

    Tong, Ya Ling; Qu, Ting Ting; Xu, Jia; Chen, Nai Yun; Yang, Mei Fang

    2017-12-01

    Infective endocarditis caused by a foreign body of the upper digestive tract is rare. We report a rare case of Granulicatella adiacens and Candida albicans coinfection acute endocarditis combined with systematic embolization caused by a fish bone from the esophagus penetrating into the left atrium. A 42-year-old woman was admitted to our hospital because of fever, abdominal pain, headache, and right limb weakness. Clinical examination indicated endocarditis and systemic embolisms secondary to a fish bone from the esophagus penetrating into the left atrium. The emergency surgery confirmed the diagnosis. Cultures of blood and vegetation show G adiacens and C albicans. Antimicrobial therapy lasted 6 weeks after surgery. The patient was discharged with excellent condition7 weeks after hospitalization and was well when followed 6 months later. The successful treatment of this patient combines quick diagnosis, timely surgery, and effective antimicrobial regimen. This rare possibility should be kept up in mind in acute infective endocarditis cases. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  8. Doubled dosage of sofosbuviris expected for inhibiting Zika virus infection

    Institute of Scientific and Technical Information of China (English)

    Somsri Wiwanitkit; Viroj Wiwanitkit

    2017-01-01

    Sofosbuvir is a new antiviral drug that has been recommended for management of hepatitis C virus (HCV) for a few years. New researches support that sofosbuvir might be useful for the management of Zika virus infection. Based on the pharmacological activity, inhibiting the HCV RNA-dependent RNA polymerase (RdRp or NS5 protein), sofosbuvir is proposed for its effectiveness against Zika virus infection. Here, the authors used a mathematical modelling theoretical approach to predict the expected dosage of sofosbuvir for inhibiting Zika virus infection. Based on the modeling study, if sofosbuvir is assigned for management of Zika virus infection, doubled dosage of the present dosage for hepatitis C management is recommended.

  9. Interplay between Candida albicans and the Mammalian Innate Host Defense

    Science.gov (United States)

    Cheng, Shih-Chin; Joosten, Leo A. B.; Kullberg, Bart-Jan

    2012-01-01

    Candida albicans is both the most common fungal commensal microorganism in healthy individuals and the major fungal pathogen causing high mortality in at-risk populations, especially immunocompromised patients. In this review, we summarize the interplay between the host innate system and C. albicans, ranging from how the host recognizes, responds, and clears C. albicans infection to how C. albicans evades, dampens, and escapes from host innate immunity. PMID:22252867

  10. A Case of Pyriform Sinus Fistula Infection with Double Tracts

    Directory of Open Access Journals (Sweden)

    Masato Shino

    2014-01-01

    Full Text Available Pyriform sinus fistula is a rare clinical entity and the precise origin remains controversial. The fistula is discovered among patients with acute suppurative thyroiditis or deep neck infection of the left side of the neck and is usually located in the left pyriform sinus. To the best of our knowledge, only a single tract has been reported to be responsible for pyriform sinus fistula infection. We present a case of a 13-year-old female patient with a pyriform sinus fistula that caused a deep infection of the left side of the neck and showed double-tract involvement discovered during surgical resection of the entire fistula. Both tracts arose around the pyriform sinus and terminated at the upper portion of the left lobe of the thyroid.

  11. Double gloving to reduce surgical cross-infection.

    Science.gov (United States)

    Tanner, J; Parkinson, H

    2006-07-19

    The invasive nature of surgery, with its increased exposure to blood, means that during surgery there is a high risk of transfer of pathogens. Pathogens can be transferred through contact between surgical patients and the surgical team, resulting in post-operative or blood borne infections in patients or blood borne infections in the surgical team. Both patients and the surgical team need to be protected from this risk. This risk can be reduced by implementing protective barriers such as wearing surgical gloves. Wearing two pairs of surgical gloves, triple gloves, glove liners or cloth outer gloves, as opposed to one pair, is considered to provide an additional barrier and further reduce the risk of contamination. The primary objective of this review was to determine if additional glove protection reduces the number of surgical site or blood borne infections in patients or the surgical team. The secondary objective was to determine if additional glove protection reduces the number of perforations to the innermost pair of surgical gloves. The innermost gloves (next to skin) compared with the outermost gloves are considered to be the last barrier between the patient and the surgical team. We searched the Cochrane Wounds Group Specialised Register (January 2006), and the Cochrane Central Register of Controlled Trials (CENTRAL)(The Cochrane Library Issue 4, 2005). We also contacted glove manufacturing companies and professional organisations. Randomised controlled trials involving: single gloving, double gloving, triple gloving, glove liners, knitted outer gloves, steel weave outer gloves and perforation indicator systems. Both authors independently assessed the relevance and quality of each trial. Data was extracted by one author and cross checked for accuracy by the second author. Two trials were found which addressed the primary outcome, namely, surgical site infections in patients. Both trials reported no infections. Thirty one randomised controlled trials

  12. Hibiscus sabdariffa extract inhibits in vitro biofilm formation capacity of Candida albicans isolated from recurrent urinary tract infections.

    Science.gov (United States)

    Alshami, Issam; Alharbi, Ahmed E

    2014-02-01

    To explore the prevention of recurrent candiduria using natural based approaches and to study the antimicrobial effect of Hibiscus sabdariffa (H. sabdariffa) extract and the biofilm forming capacity of Candida albicans strains in the present of the H. sabdariffa extract. In this particular study, six strains of fluconazole resistant Candida albicans isolated from recurrent candiduria were used. The susceptibility of fungal isolates, time-kill curves and biofilm forming capacity in the present of the H. sabdariffa extract were determined. Various levels minimum inhibitory concentration of the extract were observed against all the isolates. Minimum inhibitory concentration values ranged from 0.5 to 2.0 mg/mL. Time-kill experiment demonstrated that the effect was fungistatic. The biofilm inhibition assay results showed that H. sabdariffa extract inhibited biofilm production of all the isolates. The results of the study support the potential effect of H. sabdariffa extract for preventing recurrent candiduria and emphasize the significance of the plant extract approach as a potential antifungal agent.

  13. Comparative Phenotypic Analysis of the Major Fungal Pathogens Candida parapsilosis and Candida albicans

    Science.gov (United States)

    Holland, Linda M.; Schröder, Markus S.; Turner, Siobhán A.; Taff, Heather; Andes, David; Grózer, Zsuzsanna; Gácser, Attila; Ames, Lauren; Haynes, Ken; Higgins, Desmond G.; Butler, Geraldine

    2014-01-01

    Candida parapsilosis and Candida albicans are human fungal pathogens that belong to the CTG clade in the Saccharomycotina. In contrast to C. albicans, relatively little is known about the virulence properties of C. parapsilosis, a pathogen particularly associated with infections of premature neonates. We describe here the construction of C. parapsilosis strains carrying double allele deletions of 100 transcription factors, protein kinases and species-specific genes. Two independent deletions were constructed for each target gene. Growth in >40 conditions was tested, including carbon source, temperature, and the presence of antifungal drugs. The phenotypes were compared to C. albicans strains with deletions of orthologous transcription factors. We found that many phenotypes are shared between the two species, such as the role of Upc2 as a regulator of azole resistance, and of CAP1 in the oxidative stress response. Others are unique to one species. For example, Cph2 plays a role in the hypoxic response in C. parapsilosis but not in C. albicans. We found extensive divergence between the biofilm regulators of the two species. We identified seven transcription factors and one protein kinase that are required for biofilm development in C. parapsilosis. Only three (Efg1, Bcr1 and Ace2) have similar effects on C. albicans biofilms, whereas Cph2, Czf1, Gzf3 and Ume6 have major roles in C. parapsilosis only. Two transcription factors (Brg1 and Tec1) with well-characterized roles in biofilm formation in C. albicans do not have the same function in C. parapsilosis. We also compared the transcription profile of C. parapsilosis and C. albicans biofilms. Our analysis suggests the processes shared between the two species are predominantly metabolic, and that Cph2 and Bcr1 are major biofilm regulators in C. parapsilosis. PMID:25233198

  14. The Candida albicans Biofilm Matrix: Composition, Structure and Function.

    Science.gov (United States)

    Pierce, Christopher G; Vila, Taissa; Romo, Jesus A; Montelongo-Jauregui, Daniel; Wall, Gina; Ramasubramanian, Anand; Lopez-Ribot, Jose L

    2017-03-01

    A majority of infections caused by Candida albicans -the most frequent fungal pathogen-are associated with biofilm formation. A salient feature of C. albicans biofilms is the presence of the biofilm matrix. This matrix is composed of exopolymeric materials secreted by sessile cells within the biofilm, in which all classes of macromolecules are represented, and provides protection against environmental challenges. In this review, we summarize the knowledge accumulated during the last two decades on the composition, structure, and function of the C. albicans biofilm matrix. Knowledge of the matrix components, its structure, and function will help pave the way to novel strategies to combat C. albicans biofilm infections.

  15. Localization of extracellular matrix laminin and fibronectin in male rats infected by candida albicans, with the property expected as facilitator molecules and treated by pomegranate extract and nystatin as antifungal substance

    Energy Technology Data Exchange (ETDEWEB)

    Kumolosasi, E.S.; Barlian, A.; Sukandar, E.Y.

    1998-12-16

    Candida albicans is one of the parasitic fungi that often infects the tissue's surface in human. Nystatin has been long known as the most potent antifungal drug. One of natural products, Punica granatum, was shown to have antifungal effect as the result of ten years' investigation. In this research, male rats that were infected by C. albicans orally for 24 hours were cured by P. granatum extract with a dose of 50 mg/200 g body weight and by Nystatin 9.10{sup 3} IU/200 g body weight. Fifteen hours later, the rats were sacrificed and the small intestines were prepared for histology with semithin sectioning method. Microscopic observations showed that the inflammation occurred in the small intestines of the infected rats without any medication. However, for the rats that were treated with P. granatum extract, the small intestine area was almost in the similar condition with nin-infected rats. The small intestine of the rats treated by Nystatin showed minor inflammation. The immunocytochemistry procedure in this research still need modification to be able to detect Laminin and Fibronectin and clarify their roles in the invasion of C. albicans. (author)

  16. Beyond Candida albicans: Mechanisms of immunity to non-albicans Candida species

    Science.gov (United States)

    Whibley, Natasha; Gaffen, Sarah L.

    2015-01-01

    The fungal genus Candida encompasses numerous species that inhabit a variety of hosts, either as commensal microbes and/or pathogens. Candida species are a major cause of fungal infections, yet to date there are no vaccines against Candida or indeed any other fungal pathogen. Our knowledge of immunity to Candida mainly comes from studies on C. albicans, the most frequent species associated with disease. However, non-albicans Candida (NAC) species also cause disease and their prevalence is increasing. Although research into immunity to NAC species is still at an early stage, it is becoming apparent that immunity to C. albicans differs in important ways from non-albicans species, with important implications for treatment, therapy and predicted demographic susceptibility. This review will discuss the current understanding of immunity to NAC species in the context of immunity to C. albicans, and highlight as-yet unanswered questions. PMID:26276374

  17. In vitro modification of Candida albicans invasiveness.

    Science.gov (United States)

    Fontenla de Petrino, S E; de Jorrat, M E; Sirena, A; Valdez, J C; Mesón, O

    1986-05-01

    Candida albicans produces germ-tubes (GT) when it is incubated in animal or human serum. This dimorphism is responsible for its invasive ability. The purpose of the present paper is (1) to evaluate the ability of rat peritoneal macrophages to inhibit GT production of ingested Candida albicans, obtained from immunized rats and then activated in vitro with Candida-induced lymphokines; (2) to determinate any possible alteration of phagocytic and candidacidal activities. The phagocytes were obtained from rats immunized with viable C. albicans. Some of them were exposed to Candida-induced lymphokines in order to activate the macrophages in vitro. The monolayers of activated, immune and normal macrophages were infected with a C. albicans suspension during 4 hr. Activated macrophages presented not only the highest phagocytic and candidacidal activities but a noticeable inhibition of GT formation and incremented candidacidal activity.

  18. Emerging azole resistance among Candida albicans from clinical ...

    African Journals Online (AJOL)

    Candida albicans is one of the most frequently isolated yeasts in clinical laboratories and accounts for up to 80 % of the yeasts recovered from sites of infection. The study was set out to determine antifungal susceptibility of clinical isolates of Candida albicans and to establish the Minimum Inhibitory Concentrations (MIC) to ...

  19. Rapid and reliable MALDI-TOF mass spectrometry identification of Candida non-albicans isolates from bloodstream infections.

    Science.gov (United States)

    Pulcrano, Giovanna; Iula, Dora Vita; Vollaro, Antonio; Tucci, Alessandra; Cerullo, Monica; Esposito, Matilde; Rossano, Fabio; Catania, Maria Rosaria

    2013-09-01

    Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) fingerprinting has recently become an effective instrument for rapid microbiological diagnostics and in particular for identification of micro-organisms directly in a positive blood culture. The aim of the study was to evaluate a collection of 82 stored yeast isolates from bloodstream infection, by MALDI-TOF MS; 21 isolates were identified also directly from positive blood cultures and in the presence of other co-infecting micro-organisms. Of the 82 isolates grown on plates, 64 (76%) were correctly identified by the Vitek II system and 82 (100%) by MALDI-TOF MS; when the two methods gave different results, the isolate was identified by PCR. MALDI-TOF MS was unreliable in identifying two isolates (Candida glabrata and Candida parapsilosis) directly from blood culture; however, direct analysis from positive blood culture samples was fast and effective for the identification of yeast, which is of great importance for early and adequate treatment. © 2013. Published by Elsevier B.V. All rights reserved.

  20. Affirm VPIII microbial identification test can be used to detect gardnerella vaginalis, Candida albicans and trichomonas vaginalis microbial infections in Korean women.

    Science.gov (United States)

    Byun, Seung Won; Park, Yeon Joon; Hur, Soo Young

    2016-04-01

    The aim of this study was to compare Affirm VPIII Microbial Identification Test results for Korean women to those obtained for Gardnerella vaginalis through Nugent score, Candida albicans based on vaginal culture and Trichomonas vaginalis based on wet smear diagnostic standards. Study participants included 195 women with symptomatic or asymptomatic vulvovaginitis under hospital obstetric or gynecologic care. A definite diagnosis was made based on Nugent score for Gardnerella, vaginal culture for Candida and wet prep for Trichomonas vaginalis. Affirm VPIII Microbial Identification Test results were then compared to diagnostic standard results. Of the 195 participants, 152 were symptomatic, while 43 were asymptomatic. Final diagnosis revealed 68 (37.87%) cases of Gardnerella, 29 (14.87%) cases of Candida, one (0.51%) case of Trichomonas, and 10 (5.10%) cases of mixed infections. The detection rates achieved by each detection method (Affirm assay vs diagnostic standard) for Gardnerella and Candida were not significantly different (33.33% vs 34.8% for Gardnerella, 13.33% vs 14.87% for Candida, respectively). The sensitivity and specificity of the Affirm test for Gardnerella compared to the diagnostic standard were 75.0% and 88.98%, respectively. For Candida, the sensitivity and specificity of the Affirm test compared to the diagnostic standard were 82.76% and 98.80%, respectively. The number of Trichomonas cases was too small (1 case) to be statistically analyzed. The Affirm test is a quick tool that can help physicians diagnose and treat patients with infectious vaginitis at the point of care. © 2016 Japan Society of Obstetrics and Gynecology.

  1. Competitive Interactions between C. albicans, C. glabrata and C. krusei during Biofilm Formation and Development of Experimental Candidiasis

    Science.gov (United States)

    Rossoni, Rodnei Dennis; Barbosa, Júnia Oliveira; Vilela, Simone Furgeri Godinho; dos Santos, Jéssica Diane; de Barros, Patrícia Pimentel; Prata, Márcia Cristina de Azevedo; Anbinder, Ana Lia; Fuchs, Beth Burgwyn; Jorge, Antonio Olavo Cardoso; Mylonakis, Eleftherios; Junqueira, Juliana Campos

    2015-01-01

    In this study, we evaluated the interactions between Candida albicans, Candida krusei and Candida glabrata in mixed infections. Initially, these interactions were studied in biofilms formed in vitro. CFU/mL values of C. albicans were lower in mixed biofilms when compared to the single biofilms, verifying 77% and 89% of C. albicans reduction when this species was associated with C. glabrata and C. krusei, respectively. After that, we expanded this study for in vivo host models of experimental candidiasis. G. mellonella larvae were inoculated with monotypic and heterotypic Candida suspensions for analysis of survival rate and quantification of fungal cells in the haemolymph. In the groups with single infections, 100% of the larvae died within 18 h after infection with C. albicans. However, interaction groups achieved 100% mortality after 72 h of infection by C. albicans-C. glabrata and 96 h of infection by C. albicans-C. krusei. C. albicans CFU/mL values from larvae hemolymph were lower in the interacting groups compared with the monoespecies group after 12 h of infection. In addition, immunosuppressed mice were also inoculated with monotypic and heterotypic microbial suspensions to induce oral candidiasis. C. albicans CFU/mL values recovered from oral cavity of mice were higher in the group with single infection by C. albicans than the groups with mixed infections by C. albicans-C. glabrata and C. albicans-C. krusei. Moreover, the group with single infection by C. albicans had a higher degree of hyphae and epithelial changes in the tongue dorsum than the groups with mixed infections. We concluded that single infections by C. albicans were more harmful for animal models than mixed infections with non-albicans species, suggesting that C. albicans establish competitive interactions with C. krusei and C. glabrata during biofilm formation and development of experimental candidiasis. PMID:26146832

  2. Competitive Interactions between C. albicans, C. glabrata and C. krusei during Biofilm Formation and Development of Experimental Candidiasis.

    Science.gov (United States)

    Rossoni, Rodnei Dennis; Barbosa, Júnia Oliveira; Vilela, Simone Furgeri Godinho; dos Santos, Jéssica Diane; de Barros, Patrícia Pimentel; Prata, Márcia Cristina de Azevedo; Anbinder, Ana Lia; Fuchs, Beth Burgwyn; Jorge, Antonio Olavo Cardoso; Mylonakis, Eleftherios; Junqueira, Juliana Campos

    2015-01-01

    In this study, we evaluated the interactions between Candida albicans, Candida krusei and Candida glabrata in mixed infections. Initially, these interactions were studied in biofilms formed in vitro. CFU/mL values of C. albicans were lower in mixed biofilms when compared to the single biofilms, verifying 77% and 89% of C. albicans reduction when this species was associated with C. glabrata and C. krusei, respectively. After that, we expanded this study for in vivo host models of experimental candidiasis. G. mellonella larvae were inoculated with monotypic and heterotypic Candida suspensions for analysis of survival rate and quantification of fungal cells in the haemolymph. In the groups with single infections, 100% of the larvae died within 18 h after infection with C. albicans. However, interaction groups achieved 100% mortality after 72 h of infection by C. albicans-C. glabrata and 96 h of infection by C. albicans-C. krusei. C. albicans CFU/mL values from larvae hemolymph were lower in the interacting groups compared with the monoespecies group after 12 h of infection. In addition, immunosuppressed mice were also inoculated with monotypic and heterotypic microbial suspensions to induce oral candidiasis. C. albicans CFU/mL values recovered from oral cavity of mice were higher in the group with single infection by C. albicans than the groups with mixed infections by C. albicans-C. glabrata and C. albicans-C. krusei. Moreover, the group with single infection by C. albicans had a higher degree of hyphae and epithelial changes in the tongue dorsum than the groups with mixed infections. We concluded that single infections by C. albicans were more harmful for animal models than mixed infections with non-albicans species, suggesting that C. albicans establish competitive interactions with C. krusei and C. glabrata during biofilm formation and development of experimental candidiasis.

  3. Growth of Candida albicans hyphae.

    Science.gov (United States)

    Sudbery, Peter E

    2011-08-16

    The fungus Candida albicans is often a benign member of the mucosal flora; however, it commonly causes mucosal disease with substantial morbidity and in vulnerable patients it causes life-threatening bloodstream infections. A striking feature of its biology is its ability to grow in yeast, pseudohyphal and hyphal forms. The hyphal form has an important role in causing disease by invading epithelial cells and causing tissue damage. This Review describes our current understanding of the network of signal transduction pathways that monitors environmental cues to activate a programme of hypha-specific gene transcription, and the molecular processes that drive the highly polarized growth of hyphae.

  4. Candida albicans escapes from mouse neutrophils

    DEFF Research Database (Denmark)

    Ermert, David; Niemiec, Maria J; Röhm, Marc

    2013-01-01

    is the most widely used model organism. Neutrophils are essential immune cells to prevent opportunistic mycoses. To explore potential differences between the rodent infection model and the human host, we compared the interactions of C. albicans with neutrophil granulocytes from mice and humans. We revealed...

  5. Undecylenic Acid Inhibits Morphogenesis of Candida albicans

    OpenAIRE

    McLain, Nealoo; Ascanio, Rhoda; Baker, Carol; Strohaver, Robert A.; Dolan, Joseph W.

    2000-01-01

    Resilient liners are frequently used to treat denture stomatitis, a condition often associated with Candida albicans infections. Of 10 liners tested, 2 were found to inhibit the switch from the yeast form to hyphae and a third was found to stimulate this switch. The inhibitor was determined to be undecylenic acid.

  6. Undecylenic acid inhibits morphogenesis of Candida albicans.

    Science.gov (United States)

    McLain, N; Ascanio, R; Baker, C; Strohaver, R A; Dolan, J W

    2000-10-01

    Resilient liners are frequently used to treat denture stomatitis, a condition often associated with Candida albicans infections. Of 10 liners tested, 2 were found to inhibit the switch from the yeast form to hyphae and a third was found to stimulate this switch. The inhibitor was determined to be undecylenic acid.

  7. Polyethylene glycol-functionalized poly (Lactic Acid-co-Glycolic Acid and graphene oxide nanoparticles induce pro-inflammatory and apoptotic responses in Candida albicans-infected vaginal epithelial cells.

    Directory of Open Access Journals (Sweden)

    R Doug Wagner

    Full Text Available Mucous-penetrating nanoparticles consisting of poly lactic acid-co-glycolic acid (PLGA-polyethylene glycol (PEG could improve targeting of microbicidal drugs for sexually transmitted diseases by intravaginal inoculation. Nanoparticles can induce inflammatory responses, which may exacerbate the inflammation that occurs in the vaginal tracts of women with yeast infections. This study evaluated the effects of these drug-delivery nanoparticles on VK2(E6/E7 vaginal epithelial cell proinflammatory responses to Candida albicans yeast infections. Vaginal epithelial cell monolayers were infected with C. albicans and exposed to 100 μg/ml 49.5 nm PLGA-PEG nanospheres or 20 μg/ml 1.1 x 500 nm PEG-functionalized graphene oxide (GO-PEG sheets. The cells were assessed for changes in mRNA and protein expression of inflammation-related genes by RT-qPCR and physiological markers of cell stress using high content analysis and flow cytometry. C. albicans exposure suppressed apoptotic gene expression, but induced oxidative stress in the cells. The nanomaterials induced cytotoxicity and programmed cell death responses alone and with C. albicans. PLGA-PEG nanoparticles induced mRNA expression of apoptosis-related genes and induced poly (ADP-ribose polymerase (PARP cleavage, increased BAX/BCL2 ratios, and chromatin condensation indicative of apoptosis. They also induced autophagy, endoplasmic reticulum stress, and DNA damage. They caused the cells to excrete inflammatory recruitment molecules chemokine (C-X-C motif ligand 1 (CXCL1, interleukin-1α (IL1A, interleukin-1β (IL1B, calprotectin (S100A8, and tumor necrosis factor α (TNF. GO-PEG nanoparticles induced expression of necrosis-related genes and cytotoxicity. They reduced autophagy and endoplasmic reticulum stress, and apoptotic gene expression responses. The results show that stealth nanoparticle drug-delivery vehicles may cause intracellular damage to vaginal epithelial cells by several mechanisms and that

  8. Detecting Candida albicans in human milk.

    Science.gov (United States)

    Morrill, Jimi Francis; Pappagianis, Demosthenes; Heinig, M Jane; Lönnerdal, Bo; Dewey, Kathryn G

    2003-01-01

    Procedures for diagnosis of mammary candidosis, including laboratory confirmation, are not well defined. Lactoferrin present in human milk can inhibit growth of Candida albicans, thereby limiting the ability to detect yeast infections. The inhibitory effect of various lactoferrin concentrations on the growth of C. albicans in whole human milk was studied. The addition of iron to the milk led to a two- to threefold increase in cell counts when milk contained 3.0 mg of lactoferrin/ml and markedly reduced the likelihood of false-negative culture results. This method may provide the necessary objective support needed for diagnosis of mammary candidosis.

  9. Candida glabrata Binding to Candida albicans Hyphae Enables Its Development in Oropharyngeal Candidiasis.

    Science.gov (United States)

    Tati, Swetha; Davidow, Peter; McCall, Andrew; Hwang-Wong, Elizabeth; Rojas, Isolde G; Cormack, Brendan; Edgerton, Mira

    2016-03-01

    Pathogenic mechanisms of Candida glabrata in oral candidiasis, especially because of its inability to form hyphae, are understudied. Since both Candida albicans and C. glabrata are frequently co-isolated in oropharyngeal candidiasis (OPC), we examined their co-adhesion in vitro and observed adhesion of C. glabrata only to C. albicans hyphae microscopically. Mice were infected sublingually with C. albicans or C. glabrata individually, or with both species concurrently, to study their ability to cause OPC. Infection with C. glabrata alone resulted in negligible infection of tongues; however, colonization by C. glabrata was increased by co-infection or a pre-established infection with C. albicans. Furthermore, C. glabrata required C. albicans for colonization of tongues, since decreasing C. albicans burden with fluconazole also reduced C. glabrata. C. albicans hyphal wall adhesins Als1 and Als3 were important for in vitro adhesion of C. glabrata and to establish OPC. C. glabrata cell wall protein coding genes EPA8, EPA19, AWP2, AWP7, and CAGL0F00181 were implicated in mediating adhesion to C. albicans hyphae and remarkably, their expression was induced by incubation with germinated C. albicans. Thus, we found a near essential requirement for the presence of C. albicans for both initial colonization and establishment of OPC infection by C. glabrata.

  10. Risk factors for fatal candidemia caused by Candida albicans and non-albicans Candida species

    Directory of Open Access Journals (Sweden)

    Tang Ran-Bin

    2005-04-01

    Full Text Available Abstract Background Invasive fungal infections, such as candidemia, caused by Candida species have been increasing. Candidemia is not only associated with a high mortality (30% to 40% but also extends the length of hospital stay and increases the costs of medical care. Sepsis caused by Candida species is clinically indistinguishable from bacterial infections. Although, the clinical presentations of the patients with candidemia caused by Candida albicans and non-albicans Candida species (NAC are indistinguishable, the susceptibilities to antifungal agents of these species are different. In this study, we attempted to identify the risk factors for candidemia caused by C. albicans and NAC in the hope that this may guide initial empiric therapy. Methods A retrospective chart review was conducted during 1996 to 1999 at the Veterans General Hospital-Taipei. Results There were 130 fatal cases of candidemia, including 68 patients with C. albicans and 62 with NAC. Candidemia was the most likely cause of death in 55 of the 130 patients (42.3 %. There was no significant difference in the distribution of Candida species between those died of candidemia and those died of underlying conditions. Patients who had one of the following conditions were more likely to have C. albicans, age ≧ 65 years, immunosuppression accounted to prior use of steroids, leukocytosis, in the intensive care unit (ICU, and intravascular and urinary catheters. Patients who had undergone cancer chemotherapy often appeared less critically ill and were more likely to have NAC. Conclusion Clinical and epidemiological differences in the risk factors between candidemia caused by C. albicans and NAC may provide helpful clues to initiate empiric therapy for patients infected with C. albicans versus NAC.

  11. Risk factors for fatal candidemia caused by Candida albicans and non-albicans Candida species

    Science.gov (United States)

    Cheng, Ming-Fang; Yang, Yun-Liang; Yao, Tzy-Jyun; Lin, Chin-Yu; Liu, Jih-Shin; Tang, Ran-Bin; Yu, Kwok-Woon; Fan, Yu-Hua; Hsieh, Kai-Sheng; Ho, Monto; Lo, Hsiu-Jung

    2005-01-01

    Background Invasive fungal infections, such as candidemia, caused by Candida species have been increasing. Candidemia is not only associated with a high mortality (30% to 40%) but also extends the length of hospital stay and increases the costs of medical care. Sepsis caused by Candida species is clinically indistinguishable from bacterial infections. Although, the clinical presentations of the patients with candidemia caused by Candida albicans and non-albicans Candida species (NAC) are indistinguishable, the susceptibilities to antifungal agents of these species are different. In this study, we attempted to identify the risk factors for candidemia caused by C. albicans and NAC in the hope that this may guide initial empiric therapy. Methods A retrospective chart review was conducted during 1996 to 1999 at the Veterans General Hospital-Taipei. Results There were 130 fatal cases of candidemia, including 68 patients with C. albicans and 62 with NAC. Candidemia was the most likely cause of death in 55 of the 130 patients (42.3 %). There was no significant difference in the distribution of Candida species between those died of candidemia and those died of underlying conditions. Patients who had one of the following conditions were more likely to have C. albicans, age ≧ 65 years, immunosuppression accounted to prior use of steroids, leukocytosis, in the intensive care unit (ICU), and intravascular and urinary catheters. Patients who had undergone cancer chemotherapy often appeared less critically ill and were more likely to have NAC. Conclusion Clinical and epidemiological differences in the risk factors between candidemia caused by C. albicans and NAC may provide helpful clues to initiate empiric therapy for patients infected with C. albicans versus NAC. PMID:15813977

  12. Farnesol signalling in Candida albicans - more than just communication.

    Science.gov (United States)

    Polke, Melanie; Leonhardt, Ines; Kurzai, Oliver; Jacobsen, Ilse D

    2018-03-01

    Candida albicans is a successful colonizer of the human host, which can, under certain circumstances cause a range of clinically diverse infections. Important virulence-associated traits of the fungus, such as the dimorphic switch and biofilm formation, are controlled by the quorum sensing molecule farnesol. Given the potential of farnesol as a novel antifungal drug, there has been increasing research into the mechanism underlying farnesol sensing and action in C. albicans. However, despite the identification of various factors involved in farnesol signalling, its exact mode of action remains largely unclear. This review provides an overview of the currently known aspects of farnesol production, sensing and action within C. albicans. We also illustrate the characteristic of C. albicans to simultaneously produce and tolerate high farnesol concentrations that are lethal to other microbes. Furthermore, we summarize new literature on the role of farnesol in the interaction of C. albicans with the human host and highlight its action as a potent immunomodulatory molecule.

  13. Superoxide dismutases and glutaredoxins have a distinct role in the response of Candida albicans to oxidative stress generated by the chemical compounds menadione and diamide.

    Science.gov (United States)

    Chaves, Guilherme Maranhão; da Silva, Walicyranison Plinio

    2012-12-01

    To cope with oxidative stress, Candida albicans possesses several enzymes involved in a number of biological processes, including superoxide dismutases (Sods) and glutaredoxins (Grxs). The resistance of C. albicans to reactive oxygen species is thought to act as a virulence factor. Genes such as SOD1 and GRX2, which encode for a Sod and Grx, respectively, in C. albicans are widely recognised to be important for pathogenesis. We generated a double mutant, Δgrx2/sod1, for both genes. This strain is very defective in hyphae formation and is susceptible to killing by neutrophils. When exposed to two compounds that generate reactive oxygen species, the double null mutant was susceptible to menadione and resistant to diamide. The reintegration of the SOD1 gene in the null mutant led to recovery in resistance to menadione, whereas reintegration of the GRX2 gene made the null mutant sensitive to diamide. Despite having two different roles in the responses to oxidative stress generated by chemical compounds, GRX2 and SOD1 are important for C. albicans pathogenesis because the double mutant Δgrx2/sod1 was very susceptible to neutrophil killing and was defective in hyphae formation in addition to having a lower virulence in an animal model of systemic infection.

  14. Superoxide dismutases and glutaredoxins have a distinct role in the response of Candida albicans to oxidative stress generated by the chemical compounds menadione and diamide

    Directory of Open Access Journals (Sweden)

    Guilherme Maranhão Chaves

    2012-12-01

    Full Text Available To cope with oxidative stress, Candida albicans possesses several enzymes involved in a number of biological processes, including superoxide dismutases (Sods and glutaredoxins (Grxs. The resistance of C. albicans to reactive oxygen species is thought to act as a virulence factor. Genes such as SOD1 and GRX2, which encode for a Sod and Grx, respectively, in C. albicans are widely recognised to be important for pathogenesis. We generated a double mutant, Δgrx2/sod1, for both genes. This strain is very defective in hyphae formation and is susceptible to killing by neutrophils. When exposed to two compounds that generate reactive oxygen species, the double null mutant was susceptible to menadione and resistant to diamide. The reintegration of the SOD1 gene in the null mutant led to recovery in resistance to menadione, whereas reintegration of the GRX2 gene made the null mutant sensitive to diamide. Despite having two different roles in the responses to oxidative stress generated by chemical compounds, GRX2 and SOD1 are important for C. albicans pathogenesis because the double mutant Δgrx2/sod1 was very susceptible to neutrophil killing and was defective in hyphae formation in addition to having a lower virulence in an animal model of systemic infection.

  15. Candida albicans versus Candida dubliniensis: Why Is C. albicans More Pathogenic?

    LENUS (Irish Health Repository)

    Moran, Gary P

    2012-01-01

    Candida albicans and Candida dubliniensis are highly related pathogenic yeast species. However, C. albicans is far more prevalent in human infection and has been shown to be more pathogenic in a wide range of infection models. Comparison of the genomes of the two species has revealed that they are very similar although there are some significant differences, largely due to the expansion of virulence-related gene families (e.g., ALS and SAP) in C. albicans, and increased levels of pseudogenisation in C. dubliniensis. Comparative global gene expression analyses have also been used to investigate differences in the ability of the two species to tolerate environmental stress and to produce hyphae, two traits that are likely to play a role in the lower virulence of C. dubliniensis. Taken together, these data suggest that C. dubliniensis is in the process of undergoing reductive evolution and may have become adapted for growth in a specialized anatomic niche.

  16. Azole Antifungal Resistance in Candida albicans and Emerging Non-albicans Candida Species

    Science.gov (United States)

    Whaley, Sarah G.; Berkow, Elizabeth L.; Rybak, Jeffrey M.; Nishimoto, Andrew T.; Barker, Katherine S.; Rogers, P. David

    2017-01-01

    Within the limited antifungal armamentarium, the azole antifungals are the most frequent class used to treat Candida infections. Azole antifungals such as fluconazole are often preferred treatment for many Candida infections as they are inexpensive, exhibit limited toxicity, and are available for oral administration. There is, however, extensive documentation of intrinsic and developed resistance to azole antifungals among several Candida species. As the frequency of azole resistant Candida isolates in the clinical setting increases, it is essential to elucidate the mechanisms of such resistance in order to both preserve and improve upon the azole class of antifungals for the treatment of Candida infections. This review examines azole resistance in infections caused by C. albicans as well as the emerging non-albicans Candida species C. parapsilosis, C. tropicalis, C. krusei, and C. glabrata and in particular, describes the current understanding of molecular basis of azole resistance in these fungal species. PMID:28127295

  17. Symbiotic Plant Peptides Eliminate Candida albicans Both In Vitro and in an Epithelial Infection Model and Inhibit the Proliferation of Immortalized Human Cells

    Directory of Open Access Journals (Sweden)

    Lilla Ördögh

    2014-01-01

    Full Text Available The increasing number of multidrug-resistant microbes now emerging necessitates the identification of novel antimicrobial agents. Plants produce a great variety of antimicrobial peptides including hundreds of small, nodule-specific cysteine-rich NCR peptides that, in the legume Medicago truncatula, govern the differentiation of endosymbiotic nitrogen fixing bacteria and, in vitro, can display potent antibacterial activities. In this study, the potential candidacidal activity of 19 NCR peptides was investigated. Cationic NCR peptides having an isoelectric point above 9 were efficient in killing Candida albicans, one of the most common fungal pathogens of humans. None of the tested NCR peptides were toxic for immortalized human epithelial cells at concentrations that effectively killed the fungus; however, at higher concentrations, some of them inhibited the division of the cells. Furthermore, the cationic peptides successfully inhibited C. albicans induced human epithelial cell death in an in vitro coculture model. These results highlight the therapeutic potential of cationic NCR peptides in the treatment of candidiasis.

  18. Streptococcus agalactiae Inhibits Candida albicans Hyphal Development and Diminishes Host Vaginal Mucosal TH17 Response

    OpenAIRE

    Xiao-Yu Yu; Fei Fu; Wen-Na Kong; Qian-Kun Xuan; Dong-Hua Wen; Xiao-Qing Chen; Yong-Ming He; Li-Hua He; Jian Guo; Ai-Ping Zhou; Yang-Hong Xi; Li-Jun Ni; Yu-Feng Yao; Wen-Juan Wu

    2018-01-01

    Streptococcus agalactiae and Candida albicans often co-colonize the female genital tract, and under certain conditions induce mucosal inflammation. The role of the interaction between the two organisms in candidal vaginitis is not known. In this study, we found that co-infection with S. agalactiae significantly attenuated the hyphal development of C. albicans, and that EFG1-Hwp1 signal pathway of C. albicans was involved in this process. In a mouse model of vulvovaginal candidiasis (VVC), the...

  19. Molecular genetic techniques for gene manipulation in Candida albicans.

    Science.gov (United States)

    Xu, Qiu-Rong; Yan, Lan; Lv, Quan-Zhen; Zhou, Mi; Sui, Xue; Cao, Yong-Bing; Jiang, Yuan-Ying

    2014-05-15

    Candida albicans is one of the most common fungal pathogen in humans due to its high frequency as an opportunistic and pathogenic fungus causing superficial as well as invasive infections in immunocompromised patients. An understanding of gene function in C. albicans is necessary to study the molecular basis of its pathogenesis, virulence and drug resistance. Several manipulation techniques have been used for investigation of gene function in C. albicans, including gene disruption, controlled gene expression, protein tagging, gene reintegration, and overexpression. In this review, the main cassettes containing selectable markers used for gene manipulation in C. albicans are summarized; the advantages and limitations of these cassettes are discussed concerning the influences on the target gene expression and the virulence of the mutant strains.

  20. Budding off: bringing functional genomics to Candida albicans

    Science.gov (United States)

    Anderson, Matthew Z.

    2016-01-01

    Candida species are the most prevalent human fungal pathogens, with Candida albicans being the most clinically relevant species. Candida albicans resides as a commensal of the human gastrointestinal tract but is a frequent cause of opportunistic mucosal and systemic infections. Investigation of C. albicans virulence has traditionally relied on candidate gene approaches, but recent advances in functional genomics have now facilitated global, unbiased studies of gene function. Such studies include comparative genomics (both between and within Candida species), analysis of total RNA expression, and regulation and delineation of protein–DNA interactions. Additionally, large collections of mutant strains have begun to aid systematic screening of clinically relevant phenotypes. Here, we will highlight the development of functional genomics in C. albicans and discuss the use of these approaches to addressing both commensalism and pathogenesis in this species. PMID:26424829

  1. Development of DNA probes for Candida albicans

    International Nuclear Information System (INIS)

    Cheung, L.L.; Hudson, J.B.

    1988-01-01

    An attempt was made to produce DNA probes that could be used as a rapid and efficient means of detecting candidiasis (invasive Candida infection) in immunocompromised patients. Whole DNA from Candida albicans was digested with restriction endonuclease, and the resulting fragments were randomly cloned into a plasmid vector. Several recombinant plasmids were evaluated for cross-hybridization to various other Candida species, other fungal DNAs, and to nonfungal DNAs. Cross reactions were observed between the probes and different yeasts, but none with unrelated DNAs. Some recombinants were genus-specific, and two of these were applied to the analysis of C. albicans growth curves. It became evident that, although both 32 P- and biotin-labelled probes could be made quite sensitive, a possible limitation in their diagnostic potential was the poor liberation of Candida DNA from cells. Thus, better methods of treatment of clinical specimens will be required before such probes will be useful in routine diagnosis

  2. Development of DNA probes for Candida albicans

    Energy Technology Data Exchange (ETDEWEB)

    Cheung, L.L.; Hudson, J.B.

    1988-07-01

    An attempt was made to produce DNA probes that could be used as a rapid and efficient means of detecting candidiasis (invasive Candida infection) in immunocompromised patients. Whole DNA from Candida albicans was digested with restriction endonuclease, and the resulting fragments were randomly cloned into a plasmid vector. Several recombinant plasmids were evaluated for cross-hybridization to various other Candida species, other fungal DNAs, and to nonfungal DNAs. Cross reactions were observed between the probes and different yeasts, but none with unrelated DNAs. Some recombinants were genus-specific, and two of these were applied to the analysis of C. albicans growth curves. It became evident that, although both /sup 32/P- and biotin-labelled probes could be made quite sensitive, a possible limitation in their diagnostic potential was the poor liberation of Candida DNA from cells. Thus, better methods of treatment of clinical specimens will be required before such probes will be useful in routine diagnosis.

  3. Candida albicans septicemia in a premature infant successfully treated with oral fluconazole

    DEFF Research Database (Denmark)

    Bodé, S; Pedersen-Bjergaard, Lars; Hjelt, K

    1992-01-01

    A premature male infant, birth-weight 1460 g, was treated successfully for a Candida albicans septicemia with orally administered fluconazole for 20 days. Dosage was 5 mg/kg/day. No side effects were seen. Fluconazole may present a major progress in treatment of invasive C. albicans infections...

  4. Evaluation of adhesion forces of Staphylococcus aureus along the length of Candida albicans hyphae

    NARCIS (Netherlands)

    Ovchinnikova, E.S.; Krom, B.P.; Busscher, H.J.; van der Mei, H.C.

    2012-01-01

    Background Candida albicans is a human fungal pathogen, able to cause both superficial and serious, systemic diseases and is able to switch from yeast cells to long, tube-like hyphae, depending on the prevailing environmental conditions. Both morphological forms of C. albicans are found in infected

  5. Evaluation of adhesion forces of Staphylococcus aureus along the length of Candida albicans hyphae

    NARCIS (Netherlands)

    Ovchinnikova, Ekaterina S.; Krom, Bastiaan P.; Busscher, Henk J.; van der Mei, Henny C.

    2012-01-01

    Background: Candida albicans is a human fungal pathogen, able to cause both superficial and serious, systemic diseases and is able to switch from yeast cells to long, tube-like hyphae, depending on the prevailing environmental conditions. Both morphological forms of C. albicans are found in infected

  6. Minocycline Inhibits Candida albicans Budded-to-Hyphal-Form Transition and Biofilm Formation.

    Science.gov (United States)

    Kurakado, Sanae; Takatori, Kazuhiko; Sugita, Takashi

    2017-09-25

    Candida albicans frequently causes bloodstream infections; its budded-to-hyphalform transition (BHT) and biofilm formation are major contributors to virulence. During an analysis of antibacterial compounds that inhibit C. albicans BHT, we found that the tetracycline derivative minocycline inhibited BHT and subsequent biofilm formation. Minocycline decreased expression of hypha-specific genes HWP1 and ECE1, and adhesion factor gene ALS3 of C. albicans. In addition, minocycline decreased cell surface hydrophobicity and the extracellular β-glucan level in biofilms. Minocycline has been widely used for catheter antibiotic lock therapy to prevent bacterial infection; this compound may also be prophylactically effective against Candida infection.

  7. The double edge to parasite escape: invasive host is less infected but more infectable.

    Science.gov (United States)

    Keogh, Carolyn L; Miura, Osamu; Nishimura, Tomohiro; Byers, James E

    2017-09-01

    Nonnative species that escape their native-range parasites may benefit not only from reduced infection pathology, but also from relaxed selection on costly immune defenses, promoting reallocation of resources toward growth or reproduction. However, benefits accruing from a reduction in defense could come at the cost of increased infection susceptibility. We conducted common garden studies of the shore crab Hemigrapsus sanguineus from highly parasitized native (Japan) populations and largely parasite-free invasive (USA) populations to test for differences in susceptibility to infection by native-range rhizocephalan parasites, and to explore differences in host resource allocation. Nonnative individuals showed at least 1.8 times greater susceptibility to infection than their native counterparts, and had reduced standing metabolic rates, suggesting that less of their energy was spent on physiological self-maintenance. Our results support an indirect advantage to parasite escape via the relaxation of costly physiological defenses. However, this advantage comes at the cost of heightened susceptibility, a trade-off of parasite escape that is seldom considered. © 2017 by the Ecological Society of America.

  8. Double-stranded RNA viral infection of Trichomonas vaginalis (TVV1) in Iranian isolates.

    Science.gov (United States)

    Khanaliha, Khadijeh; Masoumi-Asl, Hossein; Bokharaei-Salim, Farah; Tabatabaei, Azardokht; Naghdalipoor, Mehri

    2017-08-01

    The Totiviridae family includes a number of viruses that can infect protozoan parasites such as Leishmania and Giardia and fungi like Saccharomyces cerevisiae. Some isolates of Trichomonas vaginalis are also infected with one or more double-stranded RNA (dsRNA) viruses. In this study, the frequency of Trichomonas vaginalis virus (TVV1) was evaluated in Iranian isolates of T. vaginalis in Tehran, Iran. One thousand five hundred vaginal samples were collected from patients attending obstetrics and gynaecology hospitals associated with Iran University of Medical Sciences in Tehran, Iran from October 2015 to September 2016. Trichomonas vaginalis isolates were cultured in Diamond's modified medium. Nucleic acids were extracted using a DNA/RNA extraction kit and RT-PCR was performed. Among 1500 collected vaginal samples, 8 (0.53%) cases of T. vaginalis infection were found. Half (4/8) of the T. vaginalis positive cases were infected with TVV1. Phylogenetic mapping indicated that the Iranian isolates were most closely related to TVV1-OC5, TVV1-UR1. Iranian isolates of T. vaginalis were infected with TVV1. The frequency of viral infection (TVV1) in T. vaginalis isolates found in this study is higher than previously reported in Iran. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Oral candidiasis-adhesion of non-albicans Candida species

    Directory of Open Access Journals (Sweden)

    Bokor-Bratić Marija B.

    2008-01-01

    Full Text Available Oral candidiasis is an opportunistic infection caused primarily by Candida albicans. However, in recent years, species of non-albicans Candida have been implicated more frequently in mucosal infection. Candida species usually reside as commensal organisms and are part of normal oral microflora. Determining exactly how transformation from commensal to pathogen takes place and how it can be prevented is continuous challenge for clinical doctors. Candidal adherence to mucosal surfaces is considered as a critical initial step in the pathogenesis of oral candidiasis. Acrylic dentures, acting as reservoirs, play an important role in increasing the risk from Candida colonisation. Thus, this review discusses what is currently known about the adhesion of non-albicans Candida species of oral origin to buccal epithelial cells and denture acrylics.

  10. Spaceflight enhances cell aggregation and random budding in Candida albicans.

    Directory of Open Access Journals (Sweden)

    Aurélie Crabbé

    Full Text Available This study presents the first global transcriptional profiling and phenotypic characterization of the major human opportunistic fungal pathogen, Candida albicans, grown in spaceflight conditions. Microarray analysis revealed that C. albicans subjected to short-term spaceflight culture differentially regulated 452 genes compared to synchronous ground controls, which represented 8.3% of the analyzed ORFs. Spaceflight-cultured C. albicans-induced genes involved in cell aggregation (similar to flocculation, which was validated by microscopic and flow cytometry analysis. We also observed enhanced random budding of spaceflight-cultured cells as opposed to bipolar budding patterns for ground samples, in accordance with the gene expression data. Furthermore, genes involved in antifungal agent and stress resistance were differentially regulated in spaceflight, including induction of ABC transporters and members of the major facilitator family, downregulation of ergosterol-encoding genes, and upregulation of genes involved in oxidative stress resistance. Finally, downregulation of genes involved in actin cytoskeleton was observed. Interestingly, the transcriptional regulator Cap1 and over 30% of the Cap1 regulon was differentially expressed in spaceflight-cultured C. albicans. A potential role for Cap1 in the spaceflight response of C. albicans is suggested, as this regulator is involved in random budding, cell aggregation, and oxidative stress resistance; all related to observed spaceflight-associated changes of C. albicans. While culture of C. albicans in microgravity potentiates a global change in gene expression that could induce a virulence-related phenotype, no increased virulence in a murine intraperitoneal (i.p. infection model was observed under the conditions of this study. Collectively, our data represent an important basis for the assessment of the risk that commensal flora could play during human spaceflight missions. Furthermore, since the

  11. Cigarette Smoke-Exposed Candida albicans Increased Chitin Production and Modulated Human Fibroblast Cell Responses

    Directory of Open Access Journals (Sweden)

    Humidah Alanazi

    2014-01-01

    Full Text Available The predisposition of cigarette smokers for development of respiratory and oral bacterial infections is well documented. Cigarette smoke can also contribute to yeast infection. The aim of this study was to investigate the effect of cigarette smoke condensate (CSC on C. albicans transition, chitin content, and response to environmental stress and to examine the interaction between CSC-pretreated C. albicans and normal human gingival fibroblasts. Following exposure to CSC, C. albicans transition from blastospore to hyphal form increased. CSC-pretreated yeast cells became significantly (P<0.01 sensitive to oxidation but significantly (P<0.01 resistant to both osmotic and heat stress. CSC-pretreated C. albicans expressed high levels of chitin, with 2- to 8-fold recorded under hyphal conditions. CSC-pretreated C. albicans adhered better to the gingival fibroblasts, proliferated almost three times more and adapted into hyphae, while the gingival fibroblasts recorded a significantly (P<0.01 slow growth rate but a significantly higher level of IL-1β when in contact with CSC-pretreated C. albicans. CSC was thus able to modulate both C. albicans transition through the cell wall chitin content and the interaction between C. albicans and normal human gingival fibroblasts. These findings may be relevant to fungal infections in the oral cavity in smokers.

  12. Interplay between the gastric bacterial microbiota and Candida albicans during postantibiotic recolonization and gastritis.

    Science.gov (United States)

    Mason, Katie L; Erb Downward, John R; Falkowski, Nicole R; Young, Vincent B; Kao, John Y; Huffnagle, Gary B

    2012-01-01

    The indigenous bacterial microbiome of the stomach, including lactobacilli, is vital in promoting colonization resistance against Candida albicans. However, there are gaps in our understanding about C. albicans gastric colonization versus disease, especially during the postantibiotic recovery phase. This study compared the gastric responses to C. albicans strains CHN1 and SC5314 in microbiome-disturbed and germfree mice to elucidate the contribution of the indigenous microbiota in C. albicans colonization versus disease and yeast-bacterium antagonism during the post-cefoperazone recolonization period. C. albicans can prevent the regrowth of Lactobacillus spp. in the stomach after cefoperazone and promote increased colonization by Enterococcus spp. Using a culture-independent analysis, the effects of oral cefoperazone on the gastric bacterial microbiota were observed to last at least 3 weeks after the cessation of the antibiotic. Disturbance of the gastric bacterial community by cefoperazone alone was not sufficient to cause gastritis, C. albicans colonization was also needed. Gastritis was not evident until after day 7 in cefoperazone-treated infected mice. In contrast, in germfree mice which lack a gastric microbiota, C. albicans induced gastric inflammation within 1 week of inoculation. Therefore, the gastric bacterial community in cefoperazone-treated mice during the first week of postantibiotic recolonization was sufficient to prevent the development of gastritis, despite being ineffective at conferring colonization resistance against C. albicans. Altogether, these data implicate a dichotomy between C. albicans colonization and gastric disease that is bacterial microbiome dependent.

  13. Candida albicans osteomyelitis of the cervical spine

    International Nuclear Information System (INIS)

    Cha, Jang-Gyu; Hong, Hyun-Sook; Koh, Yoon-Woo; Kim, Hee-Kyung; Park, Jung-Mi

    2008-01-01

    Fungal osteomyelitis is a rare infection that usually develops in immunocompromised patients. Additionally, involvement of the cervical spine by Candida albicans is extremely rare; only three previous cases of Candida vertebral osteomyelitis have been reported in the literature. The diagnosis may be delayed due to nonspecific radiologic findings and a slow progression. We report the CT, MRI, bone scan, and PET-CT findings in a patient who developed Candida osteomyelitis, which was initially misdiagnosed as metastasis, at the atlas and axis following treatment for nasopharyngeal cancer. (orig.)

  14. Iron supplementation in HIV-infected Malawian children with anemia: a double-blind, randomized, controlled trial

    NARCIS (Netherlands)

    Esan, Michael O.; van Hensbroek, Michael Boele; Nkhoma, Ernest; Musicha, Crispin; White, Sarah A.; ter Kuile, Feiko O.; Phiri, Kamija S.

    2013-01-01

    It is unknown whether iron supplementation in human immunodeficiency virus (HIV)-infected children living in regions with high infection pressure is safe or beneficial. A 2-arm, double-blind, randomized, controlled trial was conducted to examine the effects of iron supplementation on hemoglobin, HIV

  15. Double vs single internal thoracic artery harvesting in diabetic patients: role in perioperative infection rate

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    Parolari Alessandro

    2008-06-01

    Full Text Available Abstract Background The aim of this prospective study is to evaluate the role in the onset of surgical site infections of bilateral internal thoracic arteries harvesting in patients with decompensated preoperative glycemia. Methods 81 consecutive patients with uncontrolled diabetes mellitus underwent elective CABG harvesting single or double internal thoracic arteries. Single left ITA was harvested in 41 patients (Group 1, 50.6%, BITAs were harvested in 40 (Group 2, 49.4%. The major clinical end points analyzed in this study were infection rate, type of infection, duration of infection, infection relapse rate and total hospital length of stay. Results Five patients developed sternal SSI in the perioperative period, 2 in group 1 and 3 in group 2 without significant difference. All sternal SSIs were superficial with no sternal dehiscence. The development of infection from the time of surgery took 18.5 ± 2.1 and 7.3 ± 3.0 days for Groups 1 and 2 respectively. The infections were treated with wound irrigation and debridement, and with VAC therapy as well as with antibiotics. The VAC system was removed after a mean of 12.8 ± 5.1 days, when sterilization was achieved. The overall survival estimate at 1 year was 98.7%. Only BMI was a significant predictor of SSI using multivariate stepwise logistic regression analysis (Odds Ratio: 1.34; 95%Conficdence Interval: 1.02–1.83; p value: 0.04. In the model, the use of BITA was not an independent predictor of SSI. Conclusion CABG with bilateral pedicled ITAs grafting could be performed safely even in diabetics with poor preoperative glycaemic control.

  16. Albicans candidiasis amongs women and infants at two health ...

    African Journals Online (AJOL)

    Albicans candidiasis amongs women and infants at two health facilities in Port ... and in infants – Oral Thrush (OT) was investigated in Port Harcourt, Rivers State. ... UPTH (28.6%) had more infection rate than BMSH (22.9%), pregnant women ...

  17. Differentiation between Candida albicans and Candida dubliniensis using hypertonic Sabouraud broth and tobacco agar

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    Fabíola Silveira-Gomes

    2011-08-01

    Full Text Available INTRODUCTION: Opportunistic fungal infections in immunocompromised hosts are caused by Candida species, and the majority of such infections are due to Candida albicans. However, the emerging pathogen Candida dubliniensis demonstrates several phenotypic characteristics in common with C. albicans, such as production of germ tubes and chlamydospores, calling attention to the development of stable resistance to fluconazole in vitro. The aim of this study was to evaluate the performance of biochemistry identification in the differentiating between C. albicans and C. dubliniensis, by phenotyping of yeast identified as C. albicans. METHODS: Seventy-nine isolates identified as C. albicans by the API system ID 32C were grown on Sabouraud dextrose agar at 30°C for 24-48h and then inoculated on hypertonic Sabouraud broth and tobacco agar. RESULTS: Our results showed that 17 (21.5% isolates were growth-inhibited on hypertonic Sabouraud broth, a phenotypic trait inconsistent with C. albicans in this medium. However, the results observed on tobacco agar showed that only 9 (11.4% of the growth-inhibited isolates produced characteristic colonies of C. dubliniensis (rough colonies, yellowish-brown with abundant fragments of hyphae and chlamydospores. CONCLUSIONS: The results suggest that this method is a simple tool for screening C. albicans and non-albicans yeast and for verification of automated identification.

  18. Differentiation between Candida albicans and Candida dubliniensis using hypertonic Sabouraud broth and tobacco agar.

    Science.gov (United States)

    Silveira-Gomes, Fabíola; Sarmento, Dayse Nogueira; Espírito-Santo, Elaine Patrícia Tavares do; Souza, Nádia de Oliveira; Pinto, Thifany Mendes; Marques-da-Silva, Silvia Helena

    2011-01-01

    Opportunistic fungal infections in immunocompromised hosts are caused by Candida species, and the majority of such infections are due to Candida albicans. However, the emerging pathogen Candida dubliniensis demonstrates several phenotypic characteristics in common with C. albicans, such as production of germ tubes and chlamydospores, calling attention to the development of stable resistance to fluconazole in vitro. The aim of this study was to evaluate the performance of biochemistry identification in the differentiating between C. albicans and C. dubliniensis, by phenotyping of yeast identified as C. albicans. Seventy-nine isolates identified as C. albicans by the API system ID 32C were grown on Sabouraud dextrose agar at 30°C for 24-48h and then inoculated on hypertonic Sabouraud broth and tobacco agar. Our results showed that 17 (21.5%) isolates were growth-inhibited on hypertonic Sabouraud broth, a phenotypic trait inconsistent with C. albicans in this medium. However, the results observed on tobacco agar showed that only 9 (11.4%) of the growth-inhibited isolates produced characteristic colonies of C. dubliniensis (rough colonies, yellowish-brown with abundant fragments of hyphae and chlamydospores). The results suggest that this method is a simple tool for screening C. albicans and non-albicans yeast and for verification of automated identification.

  19. White-opaque Switching in Different Mating Type-like Locus Gene Types of Clinical Candida albicans Isolates

    Science.gov (United States)

    Li, Hou-Min; Shimizu-Imanishi, Yumi; Tanaka, Reiko; Li, Ruo-Yu; Yaguchi, Takashi

    2016-01-01

    Background: Candida albicans (C. albicans) can become a pathogen causing superficial as well as life-threatening systemic infections, especially in immunocompromised patients. Many phenotypic attributes contribute to its capacity to colonize human organs. In our study, 93 C. albicans isolates from patients of various candidiasis in a hospital of China were surveyed. We aimed to investigate the white-opaque (WO) switching competence, drug sensitivity, and virulence of mating type-like (MTL) a/α isolates. Methods: Internal transcribed spacer (ITS) gene and the MTL configuration were detected in all the isolates by reverse transcription-polymerase chain reaction. White/opaque phenotype and doubling time of cell growth were determined. The minimum inhibitory concentrations of antifungal agent were measured using broth microdilution method. Results: Sixty-four isolates (69.6%) were classified to serotype A, 19 (20.6%) to serotype B, and 9 (9.8%) to serotype C. Moreover, phylogenetic analysis showed that these isolates were divided into four different subgroups of ITS genotypes. Most of our clinical isolates were MTLa/α type, while 6.8% remained MTLa or MTLα type. The frequency of opaque phenotype was 71.0% (66 isolates). Following the guidelines of Clinical and Laboratory Standards Institute M27-A3, all isolates were susceptible to caspofungin and a few (0.6–3.2%) of them showed resistance against amphotericin B, flucytosine, fluconazole, itraconazole, and voriconazole. Conclusions: From these analyses, there were comparatively more C. albicans strains classified into serotype B, and the frequency of opaque phase strains was significant in the clinical isolates from China. Genetic, phenotypic, or drug susceptibility patterns were not significantly different from previous studies. MTLa/α isolates could also undergo WO switching which facilitates their survival. PMID:27824006

  20. Psd1 Effects on Candida albicans Planktonic Cells and Biofilms

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    Sónia Gonçalves

    2017-06-01

    Full Text Available Candida albicans is an important human pathogen, causing opportunistic infections. The adhesion of planktonic cells to a substrate is the first step for biofilm development. The antimicrobial peptide (AMP Psd1 is a defensin isolated from Pisum sativum seeds. We tested the effects of this AMP on C. albicans biofilms and planktonic cells, comparing its activity with amphotericin B and fluconazole. Three C. albicans variants were studied, one of them a mutant deficient in glucosylceramide synthase, conferring resistance to Psd1 antifungal action. Atomic force microscopy (AFM was used to assess morphological and biomechanical changes on fungal cells. Surface alterations, with membrane disruption and leakage of cellular contents, were observed. Cytometry assays and confocal microscopy imaging showed that Psd1 causes cell death, in a time and concentration-dependent manner. These results demonstrate Psd1 pleiotropic action against a relevant fungal human pathogen, suggesting its use as natural antimycotic agent.

  1. Oxidative Stress Responses in the Human Fungal Pathogen, Candida albicans

    Science.gov (United States)

    da Silva Dantas, Alessandra; Day, Alison; Ikeh, Mélanie; Kos, Iaroslava; Achan, Beatrice; Quinn, Janet

    2015-01-01

    Candida albicans is a major fungal pathogen of humans, causing approximately 400,000 life-threatening systemic infections world-wide each year in severely immunocompromised patients. An important fungicidal mechanism employed by innate immune cells involves the generation of toxic reactive oxygen species (ROS), such as superoxide and hydrogen peroxide. Consequently, there is much interest in the strategies employed by C. albicans to evade the oxidative killing by macrophages and neutrophils. Our understanding of how C. albicans senses and responds to ROS has significantly increased in recent years. Key findings include the observations that hydrogen peroxide triggers the filamentation of this polymorphic fungus and that a superoxide dismutase enzyme with a novel mode of action is expressed at the cell surface of C. albicans. Furthermore, recent studies have indicated that combinations of the chemical stresses generated by phagocytes can actively prevent C. albicans oxidative stress responses through a mechanism termed the stress pathway interference. In this review, we present an up-date of our current understanding of the role and regulation of oxidative stress responses in this important human fungal pathogen. PMID:25723552

  2. The Impact of use of Double Set-up on Infection Rates in Revision Total Knee Replacement and Limb Salvage Procedures

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    Jennifer Waterman

    2015-03-01

    Full Text Available A retrospective analysis was performed to determine the impact of utilizing a double set-up procedure on reducing infection rates revision total knee and limb salvage procedures in patients with known joint infection.  Eighteen cases fit selection criteria.  The recurrence rate of infection was 5.5% which is less than reported recent literature review.   This suggests the use of a double set-up in combination with other infection reducing protocols may help further reduce recurrent infection.  Keywords: double set-up, infection, revision total knee arthroplasty, limb-salvage

  3. The effect of squalene on inflammation factors induced by candida albicans in vivo studies

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jun Haeng [Dept. of Radiology, Nambu University, Gwangju (Korea, Republic of)

    2016-09-15

    In the present study, whether squalene treatment relives inflammatory reactions induced by Candida albicans was checked. The experiment was conducted in vivo using seven experimental animals (ICR mice) per experimental group. Among C. albicans-induced inflammatory factors, TNF-α, IL-6, and NO were observed using the ELISA kits method. Through the experiment, the following conclusions were obtained. 1. In the group infected with C. albicans, it could be identified that squalene treatment was inducing NO generation in renal tissues both on the 1st and 3rd days (p < 0.05). 2. In the group pre-treated(intraperitoneal administration) with SQ (80ml/kg) once per day for seven days and infected with C. albicans, it could be identified that squalene treatment was inducing TNF-α generation in renal tissues only on the 3rd day(p < 0.05). 3. In the group pre-treated(intraperitoneal administration) with SQ (80ml/kg) once per day for seven days and infected with C. albicans, it could be identified that squalene treatment was inducing IL-6 generation in renal tissues only on the 3rd day(p < 0.05). In conclusion, it could be seen that for squalene to suppress C. albicans-induced inflammatory factors, preemptively supplying SQ should be effective. Therefore, effects for recovery from C. albicans-induced immunodepression can be expected from SQ treatment.

  4. Deficiency of Double-Strand DNA Break Repair Does Not Impair Mycobacterium tuberculosis Virulence in Multiple Animal Models of Infection

    OpenAIRE

    Heaton, Brook E.; Barkan, Daniel; Bongiorno, Paola; Karakousis, Petros C.; Glickman, Michael S.

    2014-01-01

    Mycobacterium tuberculosis persistence within its human host requires mechanisms to resist the effector molecules of host immunity, which exert their bactericidal effects through damaging pathogen proteins, membranes, and DNA. Substantial evidence indicates that bacterial pathogens, including M. tuberculosis, require DNA repair systems to repair the DNA damage inflicted by the host during infection, but the role of double-strand DNA break (DSB) repair systems is unclear. Double-strand DNA bre...

  5. A novel immune evasion strategy of candida albicans: proteolytic cleavage of a salivary antimicrobial peptide.

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    Timothy F Meiller

    Full Text Available Oropharyngeal candidiasis is an opportunistic infection considered to be a harbinger of AIDS. The etiologic agent Candida albicans is a fungal species commonly colonizing human mucosal surfaces. However, under conditions of immune dysfunction, colonizing C. albicans can become an opportunistic pathogen causing superficial or even life-threatening infections. The reasons behind this transition, however, are not clear. In the oral cavity, salivary antimicrobial peptides are considered to be an important part of the host innate defense system in the prevention of microbial colonization. Histatin-5 specifically has exhibited potent activity against C. albicans. Our previous studies have shown histatin-5 levels to be significantly reduced in the saliva of HIV+ individuals, indicating an important role for histatin-5 in keeping C. albicans in its commensal stage. The versatility in the pathogenic potential of C. albicans is the result of its ability to adapt through the regulation of virulence determinants, most notably of which are proteolytic enzymes (Saps, involved in tissue degradation. In this study, we show that C. albicans cells efficiently and rapidly degrade histatin-5, resulting in loss of its anti-candidal potency. In addition, we demonstrate that this cellular activity is due to proteolysis by a member of the secreted aspartic proteases (Sap family involved in C. albicans pathogenesis. Specifically, the proteolysis was attributed to Sap9, in turn identifying histatin-5 as the first host-specific substrate for that isoenzyme. These findings demonstrate for the first time the ability of a specific C. albicans enzyme to degrade and deactivate a host antimicrobial peptide involved in the protection of the oral mucosa against C. albicans, thereby providing new insights into the factors directing the transition of C. albicans from commensal to pathogen, with important clinical implications for alternative therapy. This report characterizes the

  6. Otite externe maligne à Candida Albicans

    Science.gov (United States)

    Elayoubi, Fahd; Lachkar, Azeddine; Aabach, Ahmed; Chouai, Mohamed; Ghailan, Mohamed Rachid

    2016-01-01

    L’otite externe maligne est une ostéomyélite de la base du crane. Le Pseudomonas aeruginosa est le germe le plus incriminé. Cependant l’origine fongique n’est pas rare. Patiente âgée de 80 ans avait présenté une otalgie gauche persistante depuis deux mois malgré un traitement bien conduit. L’examen otologique mettait en évidence des signes inflammatoires au niveau du pavillon, une sténose du conduit avec des granulomes, et otorrhée d’allure purulente. Le scanner montrait un comblement otomastoïdien, un processus inflammatoire extensif des tissus pré et rétro-auriculaire et une lyse du tympanal. Vu l’absence d’amélioration un examen mycologique a été réalisé et qui a révélé la présence de Candida Albicans. Les cas d’otite externe maligne à Candida Albicans sont rarement rapportés. L’origine fongique doit être suspecté devant la négativité des prélèvements bactériologiques et la non amélioration malgré un traitement antibiotique bien conduit, et confirmée par des prélèvements mycologiques parfois multiples. L’otite externe maligne à Candida Albicans est une infection rare potentiellement mortelle. PMID:28154677

  7. Inhibitors of the glyoxylate cycle enzyme ICL1 in Candida albicans for potential use as antifungal agents.

    Directory of Open Access Journals (Sweden)

    Hong-Leong Cheah

    Full Text Available Candida albicans is an opportunistic pathogen that causes candidiasis in humans. In recent years, metabolic pathways in C. albicans have been explored as potential antifungal targets to treat candidiasis. The glyoxylate cycle, which enables C. albicans to survive in nutrient-limited host niches and its. Key enzymes (e.g., isocitrate lyase (ICL1, are particularly attractive antifungal targets for C. albicans. In this study, we used a new screening approach that better reflects the physiological environment that C. albicans cells experience during infection to identify potential inhibitors of ICL. Three compounds (caffeic acid (CAFF, rosmarinic acid (ROS, and apigenin (API were found to have antifungal activity against C. albicans when tested under glucose-depleted conditions. We further confirmed the inhibitory potential of these compounds against ICL using the ICL enzyme assay. Lastly, we assessed the bioavailability and toxicity of these compounds using Lipinski's rule-of-five and ADMET analysis.

  8. MDA5 Detects the Double-Stranded RNA Replicative Form in Picornavirus-Infected Cells

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    Qian Feng

    2012-11-01

    Full Text Available RIG-I and MDA5 are cytosolic RNA sensors that play a critical role in innate antiviral responses. Major advances have been made in identifying RIG-I ligands, but our knowledge of the ligands for MDA5 remains restricted to data from transfection experiments mostly using poly(I:C, a synthetic dsRNA mimic. Here, we dissected the IFN-α/β-stimulatory activity of different viral RNA species produced during picornavirus infection, both by RNA transfection and in infected cells in which specific steps of viral RNA replication were inhibited. Our results show that the incoming genomic plus-strand RNA does not activate MDA5, but minus-strand RNA synthesis and production of the 7.5 kbp replicative form trigger a strong IFN-α/β response. IFN-α/β production does not rely on plus-strand RNA synthesis and thus generation of the partially double-stranded replicative intermediate. This study reports MDA5 activation by a natural RNA ligand under physiological conditions.

  9. Proper Sterol Distribution Is Required for Candida albicans Hyphal Formation and Virulence

    OpenAIRE

    McCourt, Paula; Liu, Hsing-Yin; Parker, Josie E.; Gallo-Ebert, Christina; Donigan, Melissa; Bata, Adam; Giordano, Caroline; Kelly, Steven L.; Nickels, Joseph T.

    2016-01-01

    Candida albicans is an opportunistic fungus responsible for the majority of systemic fungal infections. Multiple factors contribute to C. albicans pathogenicity. C. albicans strains lacking CaArv1 are avirulent. Arv1 has a conserved Arv1 homology domain (AHD) that has a zinc-binding domain containing two cysteine clusters. Here, we explored the role of the CaAHD and zinc-binding motif in CaArv1-dependent virulence. Overall, we found that the CaAHD was necessary but not sufficient for cells to...

  10. A chronic hemodialysis patient with isolated pulmonary valve infective endocarditis caused by non-albicans Candida: a rare case and literature review.

    Science.gov (United States)

    Chang, Chih-Hao; Huang, Myo-Ming; Yeih, Dong-Feng; Lu, Kuo-Cheng; Hou, Yi-Chou

    2017-09-06

    Isolated pulmonary valve infective endocarditis caused by Candida is rare in chronic hemodialysis patients. The 2009 Infectious Diseases Society of America guidelines suggest the combined use of surgery and antibiotics to treat candidiasis; however, successful nonsurgical treatment of Candida endocarditis has been reported. A 63-year-old woman with end-stage kidney disease was admitted to our hospital after experiencing disorientation for 5 days. The patient was permanently bedridden because of depression, and denied active intravenous drug use. She received maintenance hemodialysis through a tunneled-cuffed catheter. An initial blood culture grew Candida guilliermondii without other bacteria. Subsequent blood cultures and tip culture of tunneled-cuffed catheter also grew C. guilliermondii, even after caspofungin replaced fluconazole. A 1.2-cm mobile mass was observed on the pulmonary valve. Surgical intervention was suggested, but the family of the patient declined because of her multiple comorbidities. The patient was discharged with a prescription of fluconazole, but she died soon after. Our patient is the first case with isolated pulmonary valve endocarditis caused by C. guilliermondii in patients with uremia. Hematologic disorders, in addition to long-term central venous catheter use, prolonged antibiotic intravenous injection, and congenital cardiac anomaly, predispose to the condition. The diagnosis "isolated" pulmonary IE is difficult, and combing surgery with antifungal antibiotics is the appropriate therapeutic management for Candida related pulmonary IE.

  11. The expression of virulence during double infections by different parasites with conflicting host exploitation and transmission strategies.

    Science.gov (United States)

    Ben-Ami, F; Rigaud, T; Ebert, D

    2011-06-01

    In many natural populations, hosts are found to be infected by more than one parasite species. When these parasites have different host exploitation strategies and transmission modes, a conflict among them may arise. Such a conflict may reduce the success of both parasites, but could work to the benefit of the host. For example, the less-virulent parasite may protect the host against the more-virulent competitor. We examine this conflict using the waterflea Daphnia magna and two of its sympatric parasites: the blood-infecting bacterium Pasteuria ramosa that transmits horizontally and the intracellular microsporidium Octosporea bayeri that can concurrently transmit horizontally and vertically after infecting ovaries and fat tissues of the host. We quantified host and parasite fitness after exposing Daphnia to one or both parasites, both simultaneously and sequentially. Under conditions of strict horizontal transmission, Pasteuria competitively excluded Octosporea in both simultaneous and sequential double infections, regardless of the order of exposure. Host lifespan, host reproduction and parasite spore production in double infections resembled those of single infection by Pasteuria. When hosts became first vertically (transovarilly) infected with O. bayeri, Octosporea was able to withstand competition with P. ramosa to some degree, but both parasites produced less transmission stages than they did in single infections. At the same time, the host suffered from reduced fecundity and longevity. Our study demonstrates that even when competing parasite species utilize different host tissues to proliferate, double infections lead to the expression of higher virulence and ultimately may select for higher virulence. Furthermore, we found no evidence that the less-virulent and vertically transmitting O. bayeri protects its host against the highly virulent P. ramosa. © 2011 The Authors. Journal of Evolutionary Biology © 2011 European Society For Evolutionary Biology.

  12. Streptococcus mutans Can Modulate Biofilm Formation and Attenuate the Virulence of Candida albicans

    Science.gov (United States)

    Barbosa, Júnia Oliveira; Rossoni, Rodnei Dennis; Vilela, Simone Furgeri Godinho; de Alvarenga, Janaína Araújo; Velloso, Marisol dos Santos; Prata, Márcia Cristina de Azevedo; Jorge, Antonio Olavo Cardoso; Junqueira, Juliana Campos

    2016-01-01

    Streptococcus mutans and Candida albicans are found together in the oral biofilms on dental surfaces, but little is known about the ecological interactions between these species. Here, we studied the effects of S. mutans UA159 on the growth and pathogencity of C. albicans. Initially, the effects of S. mutans on the biofilm formation and morphogenesis of C. albicans were tested in vitro. Next, we investigate the influence of S. mutans on pathogenicity of C. albicans using in vivo host models, in which the experimental candidiasis was induced in G. mellonella larvae and analyzed by survival curves, C. albicans count in hemolymph, and quantification of hyphae in the host tissues. In all the tests, we evaluated the direct effects of S. mutans cells, as well as the indirect effects of the subproducts secreted by this microorganism using a bacterial culture filtrate. The in vitro analysis showed that S. mutans cells favored biofilm formation by C. albicans. However, a reduction in biofilm viable cells and inhibition of hyphal growth was observed when C. albicans was in contact with the S. mutans culture filtrate. In the in vivo study, injection of S. mutans cells or S. mutans culture filtrate into G. mellonella larvae infected with C. albicans increased the survival of these animals. Furthermore, a reduction in hyphal formation was observed in larval tissues when C. albicans was associated with S. mutans culture filtrate. These findings suggest that S. mutans can secrete subproducts capable to inhibit the biofilm formation, morphogenesis and pathogenicity of C. albicans, attenuating the experimental candidiasis in G. mellonella model. PMID:26934196

  13. Oral Immunization Against Candidiasis Using Lactobacillus casei Displaying Enolase 1 from Candida albicans

    OpenAIRE

    Shibasaki, Seiji; Karasaki, Miki; Tafuku, Senji; Aoki, Wataru; Sewaki, Tomomitsu; Ueda, Mitsuyoshi

    2014-01-01

    Abstract Candidiasis is a common fungal infection that is prevalent in immunocompromised individuals. In this study, an oral vaccine against Candida albicans was developed by using the molecular display approach. Enolase 1 protein (Eno1p) of C. albicans was expressed on the Lactobacillus casei cell surface by using poly-gamma-glutamic acid synthetase complex A from Bacillus subtilis as an anchoring protein. The Eno1p-displaying L. casei cells were used to immunize mice, which were later chall...

  14. FarnesoI beyond morphogenesis controI: effect in Non- Candida albicans Candida species

    OpenAIRE

    Martins, Margarida Isabel Barros Coelho; Henriques, Mariana; Azeredo, Joana; Oliveira, Rosário

    2007-01-01

    Candididasis is one of the most important life-tbreatening opportunistic mycosis mainly occurring in individuais with impaired immunity. Although Candida albicans remains the most common fungai isolate, an increase in Non-Candida albicans Candida (NCAC) species is being reported. ln fact, Candida glabrata, Candida krusei, Candida parapsilosis and Candida tropicalis are emerging as clinically relevant pathogens. So it is of great importance to study the mechanisms of infection b...

  15. [The effects of an aroma candy on oral Candida albicans colony-forming units (CFU) and oral hygiene states in healthy elderly carrying Candida albicans].

    Science.gov (United States)

    Suzuki, Motofumi; Hayama, Kazumi; Takahashi, Miki; Ezawa, Kunio; Yamazaki, Masatoshi; Matsukawa, Taiji; Kishi, Akinobu; Satou, Nobuya; Abe, Shigeru

    2015-01-01

    In a preceding paper, we showed that aroma candy containing oligonol, capric acid, and cinnamon (cassia) powder had potent inhibitory activity against mycelial growth of Candida albicans in vitro and protective activity against murine oral candidiasis. In order to assess the effects of this candy (the test candy) on oral C. albicans colony-forming units (CFU) and oral hygiene states, a placebo-controlled double-blind crossover comparative study was performed. Twenty subjects were divided into two groups. One group ingested the test candy in the first 7 days followed by 2 weeks washing-off period, then ingested the placebo candy (control candy) for 7 days. The other group was vice versa. C. albicans CFU in all oral rinse samples from the subjects before and after 7 days ingestion of candy was measured. The degree of oral malodor in all subjects was monitored using a portable measuring instrument. The results showed no statistically significant difference between test-candy group and placebo group for C. albicans CFU. However, C. albicans CFU in test-candy group with>4,000 CFUs was significantly decreased after 7 days ingestion of test-candy (poral malodor in the test-candy group was significantly decreased after 7 days ingestion of test-candy (poral hygiene states indicated that in the test-candy group, oral malodor, glutinous feeling, and refreshing feeling significantly improved in comparison with control-candy group (poral health care of elderly carrying C. albicans.

  16. Restriction endonucleases from invasive Neisseria gonorrhoeae cause double-strand breaks and distort mitosis in epithelial cells during infection.

    Directory of Open Access Journals (Sweden)

    Linda Weyler

    Full Text Available The host epithelium is both a barrier against, and the target for microbial infections. Maintaining regulated cell growth ensures an intact protective layer towards microbial-induced cellular damage. Neisseria gonorrhoeae infections disrupt host cell cycle regulation machinery and the infection causes DNA double strand breaks that delay progression through the G2/M phase. We show that intracellular gonococci upregulate and release restriction endonucleases that enter the nucleus and damage human chromosomal DNA. Bacterial lysates containing restriction endonucleases were able to fragment genomic DNA as detected by PFGE. Lysates were also microinjected into the cytoplasm of cells in interphase and after 20 h, DNA double strand breaks were identified by 53BP1 staining. In addition, by using live-cell microscopy and NHS-ester stained live gonococci we visualized the subcellular location of the bacteria upon mitosis. Infected cells show dysregulation of the spindle assembly checkpoint proteins MAD1 and MAD2, impaired and prolonged M-phase, nuclear swelling, micronuclei formation and chromosomal instability. These data highlight basic molecular functions of how gonococcal infections affect host cell cycle regulation, cause DNA double strand breaks and predispose cellular malignancies.

  17. Restriction endonucleases from invasive Neisseria gonorrhoeae cause double-strand breaks and distort mitosis in epithelial cells during infection.

    Science.gov (United States)

    Weyler, Linda; Engelbrecht, Mattias; Mata Forsberg, Manuel; Brehwens, Karl; Vare, Daniel; Vielfort, Katarina; Wojcik, Andrzej; Aro, Helena

    2014-01-01

    The host epithelium is both a barrier against, and the target for microbial infections. Maintaining regulated cell growth ensures an intact protective layer towards microbial-induced cellular damage. Neisseria gonorrhoeae infections disrupt host cell cycle regulation machinery and the infection causes DNA double strand breaks that delay progression through the G2/M phase. We show that intracellular gonococci upregulate and release restriction endonucleases that enter the nucleus and damage human chromosomal DNA. Bacterial lysates containing restriction endonucleases were able to fragment genomic DNA as detected by PFGE. Lysates were also microinjected into the cytoplasm of cells in interphase and after 20 h, DNA double strand breaks were identified by 53BP1 staining. In addition, by using live-cell microscopy and NHS-ester stained live gonococci we visualized the subcellular location of the bacteria upon mitosis. Infected cells show dysregulation of the spindle assembly checkpoint proteins MAD1 and MAD2, impaired and prolonged M-phase, nuclear swelling, micronuclei formation and chromosomal instability. These data highlight basic molecular functions of how gonococcal infections affect host cell cycle regulation, cause DNA double strand breaks and predispose cellular malignancies.

  18. Vaginal yeast infection

    Science.gov (United States)

    Yeast infection - vagina; Vaginal candidiasis; Monilial vaginitis ... Most women have a vaginal yeast infection at some time. Candida albicans is a common type of fungus. It is often found in small amounts ...

  19. Recurrent Candida albicans Ventriculitis Treated with Intraventricular Liposomal Amphotericin B

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    Demet Toprak

    2015-01-01

    Full Text Available Central nervous system (CNS infection with Candida is rare but significant because of its high morbidity and mortality. When present, it is commonly seen among immunocompromised and hospitalized patients. Herein, we describe a case of a four-year-old boy with acute lymphoblastic leukemia (ALL who experienced recurrent Candida albicans meningitis. The patient was treated successfully with intravenous liposomal amphotericin B at first attack, but 25 days after discharge he was readmitted to hospital with symptoms of meningitis. Candida albicans was grown in CFS culture again and cranial magnetic resonance imaging (MRI showed ventriculitis. We administered liposomal amphotericin B both intravenously and intraventricularly and favorable result was achieved without any adverse effects. Intraventricular amphotericin B may be considered for the treatment of recurrent CNS Candida infections in addition to intravenous administration.

  20. Disruption of Sphingolipid Biosynthesis Blocks Phagocytosis of Candida albicans.

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    Fikadu G Tafesse

    2015-10-01

    Full Text Available The ability of phagocytes to clear pathogens is an essential attribute of the innate immune response. The role of signaling lipid molecules such as phosphoinositides is well established, but the role of membrane sphingolipids in phagocytosis is largely unknown. Using a genetic approach and small molecule inhibitors, we show that phagocytosis of Candida albicans requires an intact sphingolipid biosynthetic pathway. Blockade of serine-palmitoyltransferase (SPT and ceramide synthase-enzymes involved in sphingolipid biosynthesis- by myriocin and fumonisin B1, respectively, impaired phagocytosis by phagocytes. We used CRISPR/Cas9-mediated genome editing to generate Sptlc2-deficient DC2.4 dendritic cells, which lack serine palmitoyl transferase activity. Sptlc2-/- DC2.4 cells exhibited a stark defect in phagocytosis, were unable to bind fungal particles and failed to form a normal phagocytic cup to engulf C. albicans. Supplementing the growth media with GM1, the major ganglioside present at the cell surface, restored phagocytic activity of Sptlc2-/- DC2.4 cells. While overall membrane trafficking and endocytic pathways remained functional, Sptlc2-/- DC2.4 cells express reduced levels of the pattern recognition receptors Dectin-1 and TLR2 at the cell surface. Consistent with the in vitro data, compromised sphingolipid biosynthesis in mice sensitizes the animal to C. albicans infection. Sphingolipid biosynthesis is therefore critical for phagocytosis and in vivo clearance of C. albicans.

  1. Candida albicans importance to denture wearers. A literature review.

    Science.gov (United States)

    Gleiznys, Alvydas; Zdanavičienė, Eglė; Žilinskas, Juozas

    2015-01-01

    Opportunistic oral fungal infections have spred, especially in denture wearers. Denture stomatitis is a common inflammatory reaction, multifactorial etiology, which is usually associated with Candida species, particularly Candida albicans, due to its high virulence, ability to adhere and form biofilms on oral cavity tissues and denture surfaces. This article highlights the pathogenesis, clinical presentation, and management strategies of Candida-associated denture stomatitis commonly encountered in dental practice.

  2. Candida albicans Hom6 is a homoserine dehydrogenase involved in protein synthesis and cell adhesion

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    Pei-Wen Tsai

    2017-12-01

    Full Text Available Background/Purpose: Candida albicans is a common fungal pathogen in humans. In healthy individuals, C. albicans represents a harmless commensal organism, but infections can be life threatening in immunocompromised patients. The complete genome sequence of C. albicans is extremely useful for identifying genes that may be potential drug targets and important for pathogenic virulence. However, there are still many uncharacterized genes in the Candida genome database. In this study, we investigated C. albicans Hom6, the functions of which remain undetermined experimentally. Methods: HOM6-deleted and HOM6-reintegrated mutant strains were constructed. The mutant strains were compared with wild-type in their growth in various media and enzyme activity. Effects of HOM6 deletion on translation were further investigated by cell susceptibility to hygromycin B or cycloheximide, as well as by polysome profiling, and cell adhesion to polystyrene was also determined. Results: C. albicans Hom6 exhibits homoserine dehydrogenase activity and is involved in the biosynthesis of methionine and threonine. HOM6 deletion caused translational arrest in cells grown under amino acid starvation conditions. Additionally, Hom6 protein was found in both cytosolic and cell-wall fractions of cultured cells. Furthermore, HOM6 deletion reduced C. albicans cell adhesion to polystyrene, which is a common plastic used in many medical devices. Conclusion: Given that there is no Hom6 homologue in mammalian cells, our results provided an important foundation for future development of new antifungal drugs. Keywords: Candida albicans, cell adhesion, Hom6, homoserine dehydrogenase, protein synthesis

  3. Complement and innate immune evasion strategies of the human pathogenic fungus Candida albicans.

    Science.gov (United States)

    Luo, Shanshan; Skerka, Christine; Kurzai, Oliver; Zipfel, Peter F

    2013-12-15

    Candida albicans is a medically important fungus that can cause a wide range of diseases ranging from superficial infections to disseminated disease, which manifests primarily in immuno-compromised individuals. Despite the currently applied anti-fungal therapies, both mortality and morbidity caused by this human pathogenic fungus are still unacceptably high. Therefore new prophylactic and therapeutic strategies are urgently needed to prevent fungal infection. In order to define new targets for combating fungal disease, there is a need to understand the immune evasion strategies of C. albicans in detail. In this review, we summarize different sophisticated immune evasion strategies that are utilized by C. albicans. The description of the molecular mechanisms used for immune evasion does on one hand help to understand the infection process, and on the other hand provides valuable information to define new strategies and diagnostic approaches to fight and interfere with Candida infections. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Candida albicans induces pro-inflammatory and anti-apoptotic signals in macrophages as revealed by quantitative proteomics and phosphoproteomics

    DEFF Research Database (Denmark)

    Reales-Calderón, Jose Antonio; Sylvester, Marc; Strijbis, Karin

    2013-01-01

    Macrophages play a pivotal role in the prevention of Candida albicans infections. Yeast recognition and phagocytosis by macrophages is mediated by Pattern Recognition Receptors (PRRs) that initiate downstream signal transduction cascades by protein phosphorylation and dephosphorylation. We exposed...

  5. The opportunistic pathogen Pseudomonas aeruginosa activates the DNA double-strand break signaling and repair pathway in infected cells

    International Nuclear Information System (INIS)

    Elsen, S.; Collin-Faure, V.; Gidrol, X.; Lemercier, C.

    2013-01-01

    Highly hazardous DNA double-strand breaks can be induced in eukaryotic cells by a number of agents including pathogenic bacterial strains. We have investigated the genotoxic potential of Pseudomonas aeruginosa, an opportunistic pathogen causing devastating nosocomial infections in cystic fibrosis or immunocompromised patients. Our data revealed that infection of immune or epithelial cells by P. aeruginosa triggered DNA strand breaks and phosphorylation of histone H2AX (γH2AX), a marker of DNA double-strand breaks. Moreover, it induced formation of discrete nuclear repair foci similar to gamma-irradiation-induced foci, and containing γH2AX and 53BP1, an adaptor protein mediating the DNA-damage response pathway. Gene deletion, mutagenesis, and complementation in P. aeruginosa identified ExoS bacterial toxin as the major factor involved in γH2AX induction. Chemical inhibition of several kinases known to phosphorylate H2AX demonstrated that Ataxia Telangiectasia Mutated (ATM) was the principal kinase in P. aeruginosa-induced H2AX phosphorylation. Finally, infection led to ATM kinase activation by an auto-phosphorylation mechanism. Together, these data show for the first time that infection by P. aeruginosa activates the DNA double-strand break repair machinery of the host cells. This novel information sheds new light on the consequences of P. aeruginosa infection in mammalian cells. As pathogenic Escherichia coli or carcinogenic Helicobacter pylori can alter genome integrity through DNA double-strand breaks, leading to chromosomal instability and eventually cancer, our findings highlight possible new routes for further investigations of P. aeruginosa in cancer biology and they identify ATM as a potential target molecule for drug design. (authors)

  6. Novel insight into neutrophil immune responses by dry mass determination of Candida albicans morphotypes.

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    Ava Hosseinzadeh

    Full Text Available The common fungal pathogen Candida albicans has the ability to grow as a yeast or as a hypha and can alternate between these morphotypes. The overall biomass of both morphotypes increases with growth. However, only yeasts, but not hyphae, exist as discrete cellular entities. Multiplicity of infection (MOI is a useful parameter to determine the initial inoculum of yeasts for in vitro infection assays. Since the amount of hyphae is difficult to quantify, comparable starting conditions in such assays cannot be determined accurately for yeasts and hyphae using MOI. To circumvent this problem, we have established a set of correlation coefficients to convert fungal metabolic activity and optical density to dry mass. Using these correlations, we were able to accurately compare ROS production and IL-8 release by polymorphonuclear neutrophils upon infection with equal dry mass amounts of yeast and hyphal morphotypes. Neutrophil responses depended on the initial form of infection, irrespective of C. albicans wild-type yeasts transforming to hyphal growth during the assay. Infection with a high mass of live C. albicans yeasts resulted in lower neutrophil ROS and this decrease stems from efficient ROS detoxification by C. albicans without directly affecting the phagocyte ROS machinery. Moreover, we show that dead C. albicans induces significantly less ROS and IL-8 release than live fungi, but thimerosal-killed C. albicans were still able to detoxify neutrophil ROS. Thus, the dry mass approach presented in this study reveals neutrophil responses to different amounts and morphotypes of C. albicans and serves as a template for studies that aim to identify morphotype-specific responses in a variety of immune cells.

  7. Detection of phospholipase activity of Candida albicans and non albicans isolated from women of reproductive age with vulvovaginal candidiasis in rural area

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    S R Fule

    2015-01-01

    Full Text Available Background: Vulvovaginal candidiasis (VVC is most common accounting for 17 to 39% of symptomatic women. Both Candida albicans and non albicans Candida species are involved in VVC. Amongst various virulence factors proposed for Candida, extracellular phospholipases is one of the virulence factor implicated in its pathogenicity. With this background the present study was carried out to find the prevalence of different Candida species and to detect phospholipase producing strains isolated from symptomatic women with VVC. Materials and Methods: At least two vaginal swabs from 156 women of reproductive age with abnormal vaginal discharge were collected. Direct microscopy and Gram′s stained smear examined for presence of budding yeast and pseudo mycelia followed by isolation and identification of Candida species. Extracellular phospholipase activity was studied by inoculating all isolates on Sabouraud′s dextrose egg yolk agar (SDA medium. Results: Of the 156 women with curdy white discharge alone or in combination with other signs, 59 (37.82% women showed laboratory evidence of VVC. A total of 31 (52.54% women had curdy white discharge followed by 12 (20.33% with other signs and symptoms. C. albicans (62.59% and non albicans Candida (37.28% in a ratio of 1.68:1 were isolated. Of the 37 strains of C. albians 30 (81.08% showed the enzyme activity. Seventeen (56.66% strains showed higher Pz value of < 0.70 (++++. Conclusion: Although there may be typical clinical presentation of Candidiasis. all the patients did not show laboratory evidence of infection. Pregnancy was found to be major risk factor for development of VVC. C. albicans was prevalent species but non albicans species were also frequently isolated. Extracellular phospholipase activity was seen in C. albicans and not in non albicans Candida isolates.

  8. Commensal Protection of Staphylococcus aureus against Antimicrobials by Candida albicans Biofilm Matrix

    Science.gov (United States)

    Kong, Eric F.; Tsui, Christina; Kucharíková, Sona; Andes, David

    2016-01-01

    ABSTRACT Biofilm-associated polymicrobial infections, particularly those involving fungi and bacteria, are responsible for significant morbidity and mortality and tend to be challenging to treat. Candida albicans and Staphylococcus aureus specifically are considered leading opportunistic fungal and bacterial pathogens, respectively, mainly due to their ability to form biofilms on catheters and indwelling medical devices. However, the impact of mixed-species biofilm growth on therapy remains largely understudied. In this study, we investigated the influence of C. albicans secreted cell wall polysaccharides on the response of S. aureus to antibacterial agents in biofilm. Results demonstrated significantly enhanced tolerance for S. aureus to drugs in the presence of C. albicans or its secreted cell wall polysaccharide material. Fluorescence confocal time-lapse microscopy revealed impairment of drug diffusion through the mixed biofilm matrix. Using C. albicans mutant strains with modulated cell wall polysaccharide expression, exogenous supplementation, and enzymatic degradation, the C. albicans-secreted β-1,3-glucan cell wall component was identified as the key matrix constituent providing the bacteria with enhanced drug tolerance. Further, antibody labeling demonstrated rapid coating of the bacteria by the C. albicans matrix material. Importantly, via its effect on the fungal biofilm matrix, the antifungal caspofungin sensitized the bacteria to the drugs. Understanding such symbiotic interactions with clinical relevance between microbial species in biofilms will greatly aid in overcoming the limitations of current therapies and in defining potential new targets for treating polymicrobial infections. PMID:27729510

  9. Streptococcus agalactiae Inhibits Candida albicans Hyphal Development and Diminishes Host Vaginal Mucosal TH17 Response

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    Xiao-Yu Yu

    2018-02-01

    Full Text Available Streptococcus agalactiae and Candida albicans often co-colonize the female genital tract, and under certain conditions induce mucosal inflammation. The role of the interaction between the two organisms in candidal vaginitis is not known. In this study, we found that co-infection with S. agalactiae significantly attenuated the hyphal development of C. albicans, and that EFG1-Hwp1 signal pathway of C. albicans was involved in this process. In a mouse model of vulvovaginal candidiasis (VVC, the fungal burden and the levels of pro-inflammatory cytokines, IL-1β, IL-6 and TNF-α showed a increase on co-infection with S. agalactiae, while the level of TH17 T cells and IL-17 in the cervicovaginal lavage fluid were significantly decreased. Our results indicate that S. agalactiae inhibits C. albicans hyphal development by downregulating the expression of EFG1-Hwp1. The interaction between S. agalactiae and C. albicans may attenuate host vaginal mucosal TH17 immunity and contribute to mucosal colonization by C. albicans.

  10. Streptococcus agalactiae Inhibits Candida albicans Hyphal Development and Diminishes Host Vaginal Mucosal TH17 Response.

    Science.gov (United States)

    Yu, Xiao-Yu; Fu, Fei; Kong, Wen-Na; Xuan, Qian-Kun; Wen, Dong-Hua; Chen, Xiao-Qing; He, Yong-Ming; He, Li-Hua; Guo, Jian; Zhou, Ai-Ping; Xi, Yang-Hong; Ni, Li-Jun; Yao, Yu-Feng; Wu, Wen-Juan

    2018-01-01

    Streptococcus agalactiae and Candida albicans often co-colonize the female genital tract, and under certain conditions induce mucosal inflammation. The role of the interaction between the two organisms in candidal vaginitis is not known. In this study, we found that co-infection with S. agalactiae significantly attenuated the hyphal development of C. albicans , and that EFG1 -Hwp1 signal pathway of C. albicans was involved in this process. In a mouse model of vulvovaginal candidiasis (VVC), the fungal burden and the levels of pro-inflammatory cytokines, IL-1β, IL-6 and TNF-α showed a increase on co-infection with S. agalactiae , while the level of TH17 T cells and IL-17 in the cervicovaginal lavage fluid were significantly decreased. Our results indicate that S. agalactiae inhibits C. albicans hyphal development by downregulating the expression of EFG1 -Hwp1. The interaction between S. agalactiae and C. albicans may attenuate host vaginal mucosal TH17 immunity and contribute to mucosal colonization by C. albicans .

  11. Differential virulence of Candida albicans and C. dubliniensis: A role for Tor1 kinase?

    LENUS (Irish Health Repository)

    Sullivan, Derek J

    2011-01-01

    Candida albicans and Candida dubliniensis are two very closely related species of pathogenic yeast. C. albicans is the most prevalent species in the human gastrointestinal tract and is responsible for far more opportunistic infections in comparison with C. dubliniensis. This disparity is likely to be due to the reduced ability of C. dubliniensis to undergo the yeast to hypha transition, a change in morphology that plays an important role in C. albicans virulence. We have recently shown that hypha formation by C. dubliniensis is specifically repressed by nutrients at alkaline pH. In this article, we present new data showing that this can be partly reversed by treatment with rapamycin, an inhibitor of the nutrient sensing kinase Tor1 (Target Of Rapamycin). We also provide a speculative model to describe why C. albicans filaments more efficiently in nutrient rich environments, citing recently described data on Mds3, a pH responsive regulator of Tor1 kinase activity.

  12. Two's a crowd? Crowding effect in a parasitic castrator drives differences in reproductive resource allocation in single vs double infections.

    Science.gov (United States)

    Fong, Caitlin R; Moron, Nancy A; Kuris, Armand M

    2017-04-01

    The 'crowding effect' is a result of competition by parasites within a host for finite resources. Typically, the severity of this effect increases with increasing numbers of parasites within a host and manifests in reduced body size and thus fitness. Evidence for the crowding effect is mixed - while some have found negative effects, others have found a positive effect of increased parasite load on parasite fitness. Parasites are consumers with diverse trophic strategies reflected in their life history traits. These distinctions are useful to predict the effects of crowding. We studied a parasitic castrator, a parasite that usurps host reproductive energy and renders the host sterile. Parasitic castrators typically occur as single infections within hosts. With multiple parasitic castrators, we expect strong competition and evidence of crowding. We directly assess the effect of crowding on reproductive success in a barnacle population infected by a unique parasitic castrator, Hemioniscus balani, an isopod parasite that infects and blocks reproduction of barnacles. We find (1) strong evidence of crowding in double infections, (2) increased frequency of double infections in larger barnacle hosts with more resources and (3) perfect compensation in egg production, supporting strong space limitation. Our results document that the effects of crowding are particularly severe for this parasitic castrator, and may be applicable to other castrators that are also resource or space limited.

  13. Candida albicans-associated necrotizing vasculitis producing life-threatening gastrointestinal hemorrhage.

    LENUS (Irish Health Repository)

    Sargent, Jeremy

    2012-02-01

    Patients undergoing treatment of acute lymphoblastic leukemia are at risk for fungal infections including disseminated candidiasis. We describe a case of systemic Candida albicans infection associated with life-threatening gastrointestinal hemorrhage due to unusual necrotizing vasculitis involving the gastrointestinal tract. We explore the association between Candida and such vasculopathy.

  14. Discovery of a “White-Gray-Opaque” Tristable Phenotypic Switching System in Candida albicans: Roles of Non-genetic Diversity in Host Adaptation

    Science.gov (United States)

    Guan, Guobo; Dai, Yu; Nobile, Clarissa J.; Liang, Weihong; Cao, Chengjun; Zhang, Qiuyu; Zhong, Jin; Huang, Guanghua

    2014-01-01

    Non-genetic phenotypic variations play a critical role in the adaption to environmental changes in microbial organisms. Candida albicans, a major human fungal pathogen, can switch between several morphological phenotypes. This ability is critical for its commensal lifestyle and for its ability to cause infections. Here, we report the discovery of a novel morphological form in C. albicans, referred to as the “gray” phenotype, which forms a tristable phenotypic switching system with the previously reported white and opaque phenotypes. White, gray, and opaque cell types differ in a number of aspects including cellular and colony appearances, mating competency, secreted aspartyl proteinase (Sap) activities, and virulence. Of the three cell types, gray cells exhibit the highest Sap activity and the highest ability to cause cutaneous infections. The three phenotypes form a tristable phenotypic switching system, which is independent of the regulation of the mating type locus (MTL). Gray cells mate over 1,000 times more efficiently than do white cells, but less efficiently than do opaque cells. We further demonstrate that the master regulator of white-opaque switching, Wor1, is essential for opaque cell formation, but is not required for white-gray transitions. The Efg1 regulator is required for maintenance of the white phenotype, but is not required for gray-opaque transitions. Interestingly, the wor1/wor1 efg1/efg1 double mutant is locked in the gray phenotype, suggesting that Wor1 and Efg1 could function coordinately and play a central role in the regulation of gray cell formation. Global transcriptional analysis indicates that white, gray, and opaque cells exhibit distinct gene expression profiles, which partly explain their differences in causing infections, adaptation ability to diverse host niches, metabolic profiles, and stress responses. Therefore, the white-gray-opaque tristable phenotypic switching system in C. albicans may play a significant role in a wide

  15. Chemical screening identifies filastatin, a small molecule inhibitor of Candida albicans adhesion, morphogenesis, and pathogenesis.

    Science.gov (United States)

    Fazly, Ahmed; Jain, Charu; Dehner, Amie C; Issi, Luca; Lilly, Elizabeth A; Ali, Akbar; Cao, Hong; Fidel, Paul L; Rao, Reeta P; Kaufman, Paul D

    2013-08-13

    Infection by pathogenic fungi, such as Candida albicans, begins with adhesion to host cells or implanted medical devices followed by biofilm formation. By high-throughput phenotypic screening of small molecules, we identified compounds that inhibit adhesion of C. albicans to polystyrene. Our lead candidate compound also inhibits binding of C. albicans to cultured human epithelial cells, the yeast-to-hyphal morphological transition, induction of the hyphal-specific HWP1 promoter, biofilm formation on silicone elastomers, and pathogenesis in a nematode infection model as well as alters fungal morphology in a mouse mucosal infection assay. We term this compound filastatin based on its strong inhibition of filamentation, and we use chemical genetic experiments to show that it acts downstream of multiple signaling pathways. These studies show that high-throughput functional assays targeting fungal adhesion can provide chemical probes for study of multiple aspects of fungal pathogenesis.

  16. Candida Albicans and Non-Albicans Species as Etiological Agent of Vaginitis in Pregnant and Non-Pregnant Women

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    Mirela Babić

    2010-02-01

    Full Text Available Pregnancy represents a risk factor in the occurrence of vaginal candidosis. The objectives of our study were: to make determination of the microscopic findings of vaginal swab, frequency of Candida species in the culture of pregnant women and patients who are not pregnant, determine the Candida species in all cultures, and to determine the frequency and differences in the frequency of C. albicans and other non-albicans species. In one year study performed during 2006 year, we tested patients of Gynaecology and Obstetrics clinic of the Clinical Centre in Sarajevo and Gynaecology department of the General hospital in Sarajevo. 447 woman included in the study were separated in two groups: 203 pregnant (in the last trimester of pregnancy, and 244 non-pregnant woman in period of fertility. Each vaginal swab was examined microscopically. The yeast, number of colonies, and the species of Candida were determined on Sabouraud dextrose agar with presence of antibiotics. For determination of Candida species, we used germ tube test for detection of C. albicans, and cultivation on the selective medium and assimilation tests for detection of non-albicans species. The results indicated positive microscopic findings in the test group (40,9%, as well as greater number of positive cultures (46,8%. The most commonly detected species for both groups was C. albicans (test group 40.9% and control group 23,0%. The most commonly detected non-albicans species for the test group were C. glabrata (4,2 % and C. krusei (3,2%, and for the control group were C. glabrata (3,2% and C. parapsilosis (3,2%. The microscopic findings correlated with the number of colonies in positive cultures. In the test group, we found an increased number of yeasts (64,3%, and the pseudopyphae and blastopores by microscopic examination as an indication of infection. In the control group, we found a small number of yeasts (64,6%, in the form of blastopores, as an indication of the candida

  17. Clinical strains of Lactobacillus reduce the filamentation of Candida albicans and protect Galleria mellonella against experimental candidiasis.

    Science.gov (United States)

    Rossoni, Rodnei Dennis; Dos Santos Velloso, Marisol; Figueiredo, Lívia Mara Alves; Martins, Carolina Pistille; Jorge, Antonio Olavo Cardoso; Junqueira, Juliana Campos

    2018-05-01

    Candida albicans is the most common human fungal pathogen and can grow as yeast or filaments, depending on the environmental conditions. The filamentous form is of particular interest because it can play a direct role in adherence and pathogenicity. Therefore, the purpose of this study was to evaluate the effects of three clinical strains of Lactobacillus on C. albicans filamentation as well as their probiotic potential in pathogen-host interactions via an experimental candidiasis model study in Galleria mellonella. We used the reference strain Candida albicans ATCC 18804 and three clinical strains of Lactobacillus: L. rhamnosus strain 5.2, L. paracasei strain 20.3, and L. fermentum strain 20.4. First, the capacity of C. albicans to form hyphae was tested in vitro through association with the Lactobacillus strains. After that, we verified the ability of these strains to attenuate experimental candidiasis in a Galleria mellonella model through a survival curve assay. Regarding the filamentation assay, a significant reduction in hyphae formation of up to 57% was observed when C. albicans was incubated in the presence of the Lactobacillus strains, compared to a control group composed of only C. albicans. In addition, when the larvae were pretreated with Lactobacillus spp. prior to C. albicans infection, the survival rate of G. mellonela increased in all experimental groups. We concluded that Lactobacillus influences the growth and expression C. albicans virulence factors, which may interfere with the pathogenicity of these microorganisms.

  18. Antimicrobial effects of liquid anesthetic isoflurane on Candida albicans

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    Armstead Valerie

    2006-11-01

    Full Text Available Abstract Candida albicans is a dimorphic fungus that can grow in yeast morphology or hyphal form depending on the surrounding environment. This ubiquitous fungus is present in skin and mucus membranes as a potential pathogen that under opportunistic conditions causes a series of systemic and superficial infections known as candidiasis, moniliasis or simply candidiasis. There has been a steady increase in the prevalence of candidiasis that is expressed in more virulent forms of infection. Although candidiasis is commonly manifested as mucocutaneous disease, life-threatening systemic invasion by this fungus can occur in every part of the body. The severity of candidal infections is associated with its morphological shift such that the hyphal morphology of the fungus is most invasive. Of importance, aberrant multiplication of Candida yeast is also associated with the pathogenesis of certain mucosal diseases. In this study, we assessed the anti-candidal activity of the volatile anesthetic isoflurane in liquid form in comparison with the anti-fungal agent amphotericin B in an in vitro culture system. Exposure of C. albicans to isoflurane (0.3% volume/volume and above inhibited multiplication of yeast as well as formation of hyphae. These data suggest development of potential topical application of isoflurane for controlling a series of cutaneous and genital infections associated with this fungus. Elucidiation of the mechanism by which isoflurane effects fungal growth could offer therapeutic potential for certain systemic fungal infections.

  19. Antimicrobial activity of plant extracts on Candida albicans: An in vitro study

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    Sunitha Jagalur Doddanna

    2013-01-01

    Full Text Available Background and Objectives: Plants as sources of medicinal compounds have continued to play a predominant role in the maintenance of human health since ancient times. Even though several effective antifungal agents are available for oral candida infections, the failure is not uncommon because isolates of Candida albicans may exhibits resistance to the drug during therapy. The present study was conducted to evaluate the antimicrobial effects of few plant extracts on Candida albicans. An additional objective was to identify an alternative, inexpensive, simple, and effective method of preventing and controlling Candida albicans. Materials and Methods: Fine texture powder or paste form of leaves was soaked in sterile distilled water and 100% ethyl alcohol, which were kept in refrigerator at 4°C for 24 h. Then filtrates were prepared and kept in a hot air oven to get a black shining crystal powder/paste form. Stock solutions of plant extracts were inoculated on petri plates containing species of Candida albicans and incubated at 25 ± 2°C for 72 h. Results: Alcoholic curry leaves showed the maximum zone of inhibition on Candida albicans followed by aqueous tea leaves. The other plant extracts like alcoholic onion leaves, alcoholic tea leaves, alcoholic onion bulb, alcoholic aloe vera, and alcoholic mint leaves also inhibited the growth of Candida albicans but lesser extent. Conclusion: The present study renders few medicinal plants as an alternative medicines to the field of dentistry which can be used adjunct to conventional therapy of oral candidasis.

  20. Antibiofilm and Antihyphal Activities of Cedar Leaf Essential Oil, Camphor, and Fenchone Derivatives against Candida albicans

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    Ranjith Kumar Manoharan

    2017-08-01

    Full Text Available Candida albicans can form biofilms composed of yeast, hyphal, and pseudohyphal elements, and C. albicans cells in the hyphal stage could be a virulence factor. The present study describes the chemical composition, antibiofilm, and antihyphal activities of cedar leaf essential oil (CLEO, which was found to possess remarkable antibiofilm activity against C. albicans but not to affect its planktonic cell growth. Nineteen components were identified in CLEO by gas chromatography/mass spectrometry, and phenolics were the main constituents. Of these, camphor, fenchone, fenchyl alcohol, α-thujone, and borneol significantly reduced C. albicans biofilm formation. Notably, treatments with CLEO, camphor, or fenchyl alcohol at 0.01% clearly inhibited hyphal formation, and this inhibition appeared to be largely responsible for their antibiofilm effects. Transcriptomic analyses indicated that camphor and fenchyl alcohol downregulated some hypha-specific and biofilm related genes (ECE1, ECE2, RBT1, and EED1. Furthermore, camphor and fenchyl alcohol reduced C. albicans virulence in a Caenorhabditis elegans nematode model. These results demonstrate CLEO, camphor, and fenchyl alcohol might be useful for controlling C. albicans infections.

  1. Reduced CX3CL1 secretion contributes to the susceptibility of oral leukoplakia-associated fibroblasts to Candida albicans

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    Ran Cheng

    2016-11-01

    Full Text Available Candida leukoplakia (OLK is a kind of oral leukoplakia combined with chronic candidal infection, which plays an important role in the malignant transformation of OLK. However, little is known about the etiology, including susceptibility of leukoplakia to candidal adhesion, invasion and infection. Some antimicrobial peptides secreted by oral epithelial cells or fibroblasts potentially have antifungal activities against Candida albicans (C. albicans. In this study, we established three co-culture models to simulate different C. albicans-fibroblasts interactions during progression of candida leukoplakia. The susceptibility of oral leukoplakia-associated fibroblasts (LKAFs to C. albicans and its underlying mechanism were determined. Samples of 14 LKAFs and 10 normal fibroblasts (NFs were collected. The co-culture models showed that LKAFs had promoted the adhesion, invasion, and survival of C. albicans compared with NFs. CX3CL1, a chemokine with antifungal activity, was less abundant in LKAFs than NFs. Overexpression of CX3CL1 via transfection in LKAFs could partly restore the resistance to C. albicans. We also showed that inhibition of ERK could suppress CX3CL1 secretion. While phosphor-ERK was inhibited in LKAFs compared with NFs. Besides, the expression of a shedding enzyme for CX3CL1, disintegrin and metalloproteinase domain (ADAM 17 was decreased in LKAFs than NFs. In conclusion, LKAFs produced and secreted less CX3CL1 by inhibiting the ERK signaling pathway, thereby contributing to impaired cell resistance to C. albicans.

  2. Multilocus Sequence Typing of Pathogenic Candida albicans Isolates Collected from a Teaching Hospital in Shanghai, China: A Molecular Epidemiology Study

    Science.gov (United States)

    Li, Li; Zhang, Qiangqiang; Zhu, Junhao; Gao, Qian; Chen, Min; Zhu, Min

    2015-01-01

    Molecular typing of Candida albicans is important for studying the population structure and epidemiology of this opportunistic yeast, such as population dynamics, nosocomial infections, multiple infections and microevolution. The genetic diversity of C. albicans has been rarely studied in China. In the present study, multilocus sequence typing (MLST) was used to characterize the genetic diversity and population structure of 62 C. albicans isolates collected from 40 patients from Huashan Hospital in Shanghai, China. A total of 50 diploid sequence types (DSTs) were identified in the 62 C. albicans isolates, with 41 newly identified DSTs. Based on cluster analysis, the 62 isolates were classified into nine existing clades and two new clades (namely clades New 1 and New 2). The majority of the isolates were clustered into three clades, clade 6 (37.5%), clade 1 (15.0%) and clade 17 (15.0%). Isolates of clade New 2 were specifically identified in East Asia. We identified three cases of potential nosocomial transmission based on association analysis between patients’ clinical data and the genotypes of corresponding isolates. Finally, by analyzing the genotypes of serial isolates we further demonstrated that the microevolution of C. albicans was due to loss of heterozygosity. Our study represents the first molecular typing of C. albicans in eastern China, and we confirmed that MLST is a useful tool for studying the epidemiology and evolution of C. albicans. PMID:25919124

  3. Efek Antijamur Minyak Atsiri Jahe Merah (Zingiber officinale Var. Rubrum terhadap Candida albicans

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    Hermina Karuna Atmaja

    2015-10-01

    Full Text Available The prevalence of Candida albicans infections is increasing in the society. Therefore, an effective and affordable antifungal drug with minimal side effect is needed. Ginger (Zingiber officinale is a traditional herb which has an antifungal effect in its volatile oil. Objective: To investigate antifungal effect of volatile oil from Zingiber officinale var rubrum against C. albicans in vitro, to determine the optimum concentration, and finally to determine the correlation between the various concentrations of the oil and the inhibition zone. Material and method: Strain C. albicans tested was obtained from the Department of Parasitology, Medical Faculty, University of Indonesia. Volatile oil of Zingiber officinale var. rubrum was produced from water and steam distillation of fresh ginger in BALLITRO, Bogor. Concentrations of the volatile oil used were 100%, 50%, 25%, 12,5% 6.25%, 3.125%, 1.56% and 0.78%. Methods used were colony counting and disk diffusion method (by using 6 mm blank disk. The specimens were divided into two groups, treatment group (C. albicans with application of volatile oil and control group (C. albicans without application of volatile oil. Result: There was a significant decrease in the amount of C. albicans colonies from 3.125% to 6.25% of concentration. The amount of C. albicans colonies at concentration 6.25% was also significantly lower than in the control group. Moreover, there was strong and positive correlation between the concentration of the volatile oil and the inhibition zone. Conclusion: Volatile oil from Zingiber officinale var. rubrum has an antifungal effect against C. albicans in vitro with optimum concentration at 6.25%. Increasing concentrations of the oil correlates with increasing inhibition zome.

  4. Effect of hookworm infection on wheat challenge in celiac disease--a randomised double-blinded placebo controlled trial.

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    A James Daveson

    Full Text Available BACKGROUND AND AIMS: The association between hygiene and prevalence of autoimmune disease has been attributed in part to enteric helminth infection. A pilot study of experimental infection with the hookworm Necator americanus was undertaken among a group of otherwise healthy people with celiac disease to test the potential of the helminth to suppress the immunopathology induced by gluten. METHODS: In a 21-week, double-blinded, placebo-controlled study, we explored the effects of N. americanus infection in 20 healthy, helminth-naïve adults with celiac disease well controlled by diet. Staged cutaneous inoculations with 10 and 5 infective 3(rd stage hookworm larvae or placebo were performed at week-0 and -12 respectively. At week-20, a five day oral wheat challenge equivalent to 16 grams of gluten per day was undertaken. Primary outcomes included duodenal Marsh score and quantification of the immunodominant α-gliadin peptide (QE65-specific systemic interferon-γ-producing cells by ELISpot pre- and post-wheat challenge. RESULTS: Enteric colonisation with hookworm established in all 10 cases, resulting in transiently painful enteritis in 5. Chronic infection was asymptomatic, with no effect on hemoglobin levels. Although some duodenal eosinophilia was apparent, hookworm-infected mucosa retained a healthy appearance. In both groups, wheat challenge caused deterioration in both primary and several secondary outcomes. CONCLUSIONS: Experimental N. americanus infection proved to be safe and enabled testing its effect on a range of measures of the human autoimmune response. Infection imposed no obvious benefit on pathology. TRIAL REGISTRATION: ClinicalTrials.gov NCT00671138.

  5. Relative Abundances of Candida albicans and Candida glabrata in In Vitro Coculture Biofilms Impact Biofilm Structure and Formation.

    Science.gov (United States)

    Olson, Michelle L; Jayaraman, Arul; Kao, Katy C

    2018-04-15

    Candida is a member of the normal human microbiota and often resides on mucosal surfaces such as the oral cavity or the gastrointestinal tract. In addition to their commensality, Candida species can opportunistically become pathogenic if the host microbiota is disrupted or if the host immune system becomes compromised. An important factor for Candida pathogenesis is its ability to form biofilm communities. The two most medically important species- Candida albicans and Candida glabrata -are often coisolated from infection sites, suggesting the importance of Candida coculture biofilms. In this work, we report that biofilm formation of the coculture population depends on the relative ratio of starting cell concentrations of C. albicans and C. glabrata When using a starting ratio of C. albicans to C. glabrata of 1:3, ∼6.5- and ∼2.5-fold increases in biofilm biomass were observed relative to those of a C. albicans monoculture and a C. albicans / C. glabrata ratio of 1:1, respectively. Confocal microscopy analysis revealed the heterogeneity and complex structures composed of long C. albicans hyphae and C. glabrata cell clusters in the coculture biofilms, and reverse transcription-quantitative PCR (qRT-PCR) studies showed increases in the relative expression of the HWP1 and ALS3 adhesion genes in the C. albicans / C. glabrata 1:3 biofilm compared to that in the C. albicans monoculture biofilm. Additionally, only the 1:3 C. albicans / C. glabrata biofilm demonstrated an increased resistance to the antifungal drug caspofungin. Overall, the results suggest that interspecific interactions between these two fungal pathogens increase biofilm formation and virulence-related gene expression in a coculture composition-dependent manner. IMPORTANCE Candida albicans and Candida glabrata are often coisolated during infection, and the occurrence of coisolation increases with increasing inflammation, suggesting possible synergistic interactions between the two Candida species in

  6. Betamethasone augments the antifungal effect of menadione--towards a novel anti-Candida albicans combination therapy.

    Science.gov (United States)

    Jakab, Ágnes; Emri, Tamás; Sipos, Lilla; Kiss, Ágnes; Kovács, Renátó; Dombrádi, Viktor; Kemény-Beke, Ádám; Balla, József; Majoros, László; Pócsi, István

    2015-08-01

    The fluorinated glucocorticoid betamethasone stimulated both the extracellular phospholipase production and hypha formation of the opportunistic human pathogen Candida albicans and also decreased the efficiency of the polyene antimycotics amphotericin B and nystatin against C. albicans in a dose-dependent manner. Importantly, betamethasone increased synergistically the anti-Candida activity of the oxidative stress generating agent menadione, which may be exploited in future combination therapies to prevent or cure C. albicans infections, in the field of dermatology. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. First report of Ditylenchus gallaeformans in Miconia albicans from the Brazilian Cerrado, State of Goiás

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    Rodrigo Vieira da Silva

    2016-04-01

    Full Text Available Miconia albicans (Melastomataceae, whose common name is canela-de-velha, is a native plant of the tropical region that is abundant in the Cerrado biome. A nematode species was found parasitizing M. albicans, causing severe deformation and gall-like structures on the infected leaves and inflorescences. Morphological, morphometric and molecular characterizations identified the nematode as Ditylenchus gallaeformans. This nematode has great potential as a biocontrol agent of plants in the family Melastomataceae, which are invasive weeds in ecosystems of the Pacific Islands. This is the first report of D. gallaeformans parasitizing M. albicans in the Cerrado of the state of Goiás.

  8. Evaluation of adhesion forces of Staphylococcus aureus along the length of Candida albicans hyphae.

    Science.gov (United States)

    Ovchinnikova, Ekaterina S; Krom, Bastiaan P; Busscher, Henk J; van der Mei, Henny C

    2012-11-27

    Candida albicans is a human fungal pathogen, able to cause both superficial and serious, systemic diseases and is able to switch from yeast cells to long, tube-like hyphae, depending on the prevailing environmental conditions. Both morphological forms of C. albicans are found in infected tissue, often in combination with Staphylococcus aureus. Although bacterial adhesion to the different morphologies of C. albicans has been amply studied, possible differences in staphylococcal adhesion forces along the length of C. albicans hyphae have never been determined. In this study, we aim to verify the hypothesis that the forces mediating S. aureus NCTC8325-4GFP adhesion to hyphae vary along the length of C. albicans SC5314 and MB1 hyphae, as compared with adhesion to yeast cells. C. albicans hyphae were virtually divided into a "tip" (the growing and therefore youngest part of the hyphae), a "middle" and a so-called "head" region (the yeast cell from which germination started). Adhesion forces between S. aureus NCTC8325-4GFP and the different regions of C. albicans SC5314 hyphae were measured using atomic force microscopy. Strong adhesion forces were found at the tip and middle regions of C. albicans hyphae (-4.1 nN and -4.0 nN, respectively), while much smaller adhesion forces were measured at the head region (-0.3 nN). Adhesion forces exerted by the head region were comparable with the forces arising from budding yeast cells (-0.5 nN). A similar regional dependence of the staphylococcal adhesion forces was found for the clinical isolate involved in this study, C. albicans MB1. This is the first time that differences in adhesion forces between S. aureus and different regions of C. albicans hyphae have been demonstrated on a quantitative basis, supporting the view that the head region is different from the remainder of the hyphae. Notably it can be concluded that the properties of the hyphal head region are similar to those of budding yeast cells. These novel findings

  9. Staphylococcus aureus adherence to Candida albicans hyphae is mediated by the hyphal adhesin Als3p.

    Science.gov (United States)

    Peters, Brian M; Ovchinnikova, Ekaterina S; Krom, Bastiaan P; Schlecht, Lisa Marie; Zhou, Han; Hoyer, Lois L; Busscher, Henk J; van der Mei, Henny C; Jabra-Rizk, Mary Ann; Shirtliff, Mark E

    2012-12-01

    The bacterium Staphylococcus (St.) aureus and the opportunistic fungus Candida albicans are currently among the leading nosocomial pathogens, often co-infecting critically ill patients, with high morbidity and mortality. Previous investigations have demonstrated preferential adherence of St. aureus to C. albicans hyphae during mixed biofilm growth. In this study, we aimed to characterize the mechanism behind this observed interaction. C. albicans adhesin-deficient mutant strains were screened by microscopy to identify the specific receptor on C. albicans hyphae recognized by St. aureus. Furthermore, an immunoassay was developed to validate and quantify staphylococcal binding to fungal biofilms. The findings from these experiments implicated the C. albicans adhesin agglutinin-like sequence 3 (Als3p) in playing a major role in the adherence process. This association was quantitatively established using atomic force microscopy, in which the adhesion force between single cells of the two species was significantly reduced for a C. albicans mutant strain lacking als3. Confocal microscopy further confirmed these observations, as St. aureus overlaid with a purified recombinant Als3 N-terminal domain fragment (rAls3p) exhibited robust binding. Importantly, a strain of Saccharomyces cerevisiae heterologously expressing Als3p was utilized to further confirm this adhesin as a receptor for St. aureus. Although the parental strain does not bind bacteria, expression of Als3p on the cell surface conferred upon the yeast the ability to strongly bind St. aureus. To elucidate the implications of these in vitro findings in a clinically relevant setting, an ex vivo murine model of co-infection was designed using murine tongue explants. Fluorescent microscopic images revealed extensive hyphal penetration of the epithelium typical of C. albicans mucosal infection. Interestingly, St. aureus bacterial cells were only seen within the epithelial tissue when associated with the invasive

  10. Glycosylation of Candida albicans cell wall proteins is critical for induction of innate immune responses and apoptosis of epithelial cells.

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    Jeanette Wagener

    Full Text Available C. albicans is one of the most common fungal pathogen of humans, causing local and superficial mucosal infections in immunocompromised individuals. Given that the key structure mediating host-C. albicans interactions is the fungal cell wall, we aimed to identify features of the cell wall inducing epithelial responses and be associated with fungal pathogenesis. We demonstrate here the importance of cell wall protein glycosylation in epithelial immune activation with a predominant role for the highly branched N-glycosylation residues. Moreover, these glycan moieties induce growth arrest and apoptosis of epithelial cells. Using an in vitro model of oral candidosis we demonstrate, that apoptosis induction by C. albicans wild-type occurs in early stage of infection and strongly depends on intact cell wall protein glycosylation. These novel findings demonstrate that glycosylation of the C. albicans cell wall proteins appears essential for modulation of epithelial immunity and apoptosis induction, both of which may promote fungal pathogenesis in vivo.

  11. Culture Supernatants of Lactobacillus gasseri and L. crispatus Inhibit Candida albicans Biofilm Formation and Adhesion to HeLa Cells.

    Science.gov (United States)

    Matsuda, Yuko; Cho, Otomi; Sugita, Takashi; Ogishima, Daiki; Takeda, Satoru

    2018-03-30

    Vulvovaginal candidiasis (VVC) is a common superficial infection of the vaginal mucous membranes caused by the fungus Candida albicans. The aim of this study was to assess the mechanisms underlying the inhibitory effects of the culture supernatants of Lactobacillus gasseri and L. crispatus, the predominant microbiota in Asian healthy women, on C. albicans biofilm formation. The inhibition of C. albicans adhesion to HeLa cells by Lactobacillus culture supernatant was also investigated. Candida albicans biofilm was formed on polystyrene flat-bottomed 96-well plates, and the inhibitory effects on the initial colonization and maturation phases were determined using the XTT reduction assay. The expression levels of biofilm formation-associated genes (HWP1, ECE1, ALS3, BCR1, EFG1, TEC1, and CPH1) were determined by reverse transcription quantitative polymerase chain reaction. The inhibition of C. albicans adhesion to HeLa cells by Lactobacillus culture supernatant was evaluated by enumerating viable C. albicans cells. The culture supernatants of both Lactobacillus species inhibited the initial colonization and maturation of C. albicans biofilm. The expression levels of all biofilm formation-related genes were downregulated in the presence of Lactobacillus culture supernatant. The culture supernatant also inhibited C. albicans adhesion to HeLa cells. The culture supernatants of L. gasseri and L. crispatus inhibited C. albicans biofilm formation by downregulating biofilm formation-related genes and C. albicans adhesion to HeLa cells. These findings support the notion that Lactobacillus metabolites may be useful alternatives to antifungal drugs for the management of VVC.

  12. Postantifungal Effect of Micafungin against the Species Complexes of Candida albicans and Candida parapsilosis.

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    Sandra Gil-Alonso

    Full Text Available Micafungin is an effective antifungal agent useful for the therapy of invasive candidiasis. Candida albicans is the most common cause of invasive candidiasis; however, infections due to non-C. albicans species, such as Candida parapsilosis, are rising. Killing and postantifungal effects (PAFE are important factors in both dose interval choice and infection outcome. The aim of this study was to determinate the micafungin PAFE against 7 C. albicans strains, 5 Candida dubliniensis, 2 Candida Africana, 3 C. parapsilosis, 2 Candida metapsilosis and 2 Candida orthopsilosis. For PAFE studies, cells were exposed to micafungin for 1 h at concentrations ranging from 0.12 to 8 μg/ml. Time-kill experiments (TK were conducted at the same concentrations. Samples were removed at each time point (0-48 h and viable counts determined. Micafungin (2 μg/ml was fungicidal (≥ 3 log10 reduction in TK against 5 out of 14 (36% strains of C. albicans complex. In PAFE experiments, fungicidal endpoint was achieved against 2 out of 14 strains (14%. In TK against C. parapsilosis, 8 μg/ml of micafungin turned out to be fungicidal against 4 out 7 (57% strains. Conversely, fungicidal endpoint was not achieved in PAFE studies. PAFE results for C. albicans complex (41.83 ± 2.18 h differed from C. parapsilosis complex (8.07 ± 4.2 h at the highest tested concentration of micafungin. In conclusion, micafungin showed significant differences in PAFE against C. albicans and C. parapsilosis complexes, being PAFE for the C. albicans complex longer than for the C. parapsilosis complex.

  13. Diagnosis of vaginal infection in pregnancy | Botha | Health SA ...

    African Journals Online (AJOL)

    In 51,4% of the cases the diagnosis differed. Candida albicans infection was diagnosed by 10 respondents, while 3 actually had Trichomonas vaginalis infection and seven had Gardnerella vaginalis infection. Trichomonas vaginalis infection was diagnosed in 26 cases, while 15 were actually due to Candida albicans and ...

  14. Melanocytes and melanin represent a first line of innate immunity against Candida albicans.

    Science.gov (United States)

    Tapia, Cecilia V; Falconer, Maryanne; Tempio, Fabián; Falcón, Felipe; López, Mercedes; Fuentes, Marisol; Alburquenque, Claudio; Amaro, José; Bucarey, Sergio A; Di Nardo, Anna

    2014-07-01

    Melanocytes are dendritic cells located in the skin and mucosae that synthesize melanin. Some infections induce hypo- or hyperpigmentation, which is associated with the activation of Toll-like receptors (TLRs), especially TLR4. Candida albicans is an opportunist pathogen that can switch between blastoconidia and hyphae forms; the latter is associated with invasion. Our objectives in this study were to ascertain whether C. albicans induces pigmentation in melanocytes and whether this process is dependent on TLR activation, as well as relating this with the antifungal activity of melanin as a first line of innate immunity against fungal infections. Normal human melanocytes were stimulated with C. albicans supernatants or with crude extracts of the blastoconidia or hyphae forms, and pigmentation and TLR2/TLR4 expression were measured. Expression of the melanosomal antigens Melan-A and gp100 was examined for any correlation with increased melanin levels or antifungal activity in melanocyte lysates. Melanosomal antigens were induced earlier than cell pigmentation, and hyphae induced stronger melanization than blastoconidia. Notably, when melanocytes were stimulated with crude extracts of C. albicans, the cell surface expression of TLR2/TLR4 began at 48 h post-stimulation and peaked at 72 h. At this time, blastoconidia induced both TLR2 and TLR4 expression, whereas hyphae only induced TLR4 expression. Taken together, these results suggest that melanocytes play a key role in innate immune responses against C. albicans infections by recognizing pathogenic forms of C. albicans via TLR4, resulting in increased melanin content and inhibition of infection. © The Author 2014. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. Miltefosine inhibits Candida albicans and non-albicans Candida spp. biofilms and impairs the dispersion of infectious cells.

    Science.gov (United States)

    Vila, Taissa; Ishida, Kelly; Seabra, Sergio Henrique; Rozental, Sonia

    2016-11-01

    Candida spp. can adhere to and form biofilms over different surfaces, becoming less susceptible to antifungal treatment. Resistance of biofilms to antifungal agents is multifactorial and the extracellular matrix (ECM) appears to play an important role. Among the few available antifungals for treatment of candidaemia, only the lipid formulations of amphotericin B (AmB) and the echinocandins are effective against biofilms. Our group has previously demonstrated that miltefosine has an important effect against Candida albicans biofilms. Thus, the aim of this work was to expand the analyses of the in vitro antibiofilm activity of miltefosine to non-albicans Candida spp. Miltefosine had significant antifungal activity against planktonic cells and the development of biofilms of C. albicans, Candida parapsilosis, Candida tropicalis and Candida glabrata. The activity profile in biofilms was superior to fluconazole and was similar to that of AmB and caspofungin. Biofilm-derived cells with their ECM extracted became as susceptible to miltefosine as planktonic cells, confirming the importance of the ECM in the biofilm resistant behaviour. Miltefosine also inhibited biofilm dispersion of cells at the same concentration needed to inhibit planktonic cell growth. The data obtained in this work reinforce the potent inhibitory activity of miltefosine on biofilms of the four most pathogenic Candida spp. and encourage further studies for the utilisation of this drug and/or structural analogues on biofilm-related infections. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  16. Effect of Low-Level Laser therapy on the fungal proliferation of Candida albicans

    Science.gov (United States)

    Carneiro, Vanda S. M.; Araújo, Natália C.; Menezes, Rebeca F. d.; Moreno, Lara M.; Santos-Neto, Alexandrino d. P.; Gerbi, Marleny Elizabeth M.

    2016-03-01

    Candida albicans plays an important role in triggering infections in HIV+ patients. The indiscriminate use of antifungals has led to resistance to Candida albicans, which requires new treatment alternatives for oral candidiasis. Low-level laser therapy promotes a considerable improvement in the healing of wounds and in curing illnesses caused by microorganisms. The aim of the present study was to assess the effect of laser radiation on the cell proliferation of Candida albicans in immunosuppressed patients. Six Candida albicans strains that had been isolated from immunosuppressed patients were divided into a control group and experimental groups, which received eight sessions of laser therapy (InGaAlP, λ685nm, P = 30mW, CW, Φ~6 mm and GaAlAs, λ830nm, P = 40mW, CW, Φ~6 mm) using dosimetries of 6J/cm2, 8J/cm2, 10J/cm2 and 12J/cm2 for each wavelength and power. The results were not statistically significant (Kruskal Wallis, p > 0.05), although the proliferation of Candida albicans was lower in some of the experimental groups. The dosimetry of 6J/cm2 (GaAlAs, λ830nm, P = 40mW) provided lower mean scores than the other groups for the growth of Candida. Further studies are required to confirm whetehr laser therapy is a viable option in the treatment of fungal infections.

  17. Identification of virulence determinants of the human pathogenic fungi Aspergillus fumigatus and Candida albicans by proteomics.

    Science.gov (United States)

    Kniemeyer, Olaf; Schmidt, André D; Vödisch, Martin; Wartenberg, Dirk; Brakhage, Axel A

    2011-06-01

    Both fungi Candida albicans and Aspergillus fumigatus can cause a number of life-threatening systemic infections in humans. The commensal yeast C. albicans is one of the main causes of nosocomial fungal infectious diseases, whereas the filamentous fungus A. fumigatus has become one of the most prevalent airborne fungal pathogens. Early diagnosis of these fungal infections is challenging, only a limited number of antifungals for treatment are available, and the molecular details of pathogenicity are hardly understood. The completion of both the A. fumigatus and C. albicans genome sequence provides the opportunity to improve diagnosis, to define new drug targets, to understand the functions of many uncharacterised proteins, and to study protein regulation on a global scale. With the application of proteomic tools, particularly two-dimensional gel electrophoresis and LC/MS-based methods, a comprehensive overview about the proteins of A. fumigatus and C. albicans present or induced during environmental changes and stress conditions has been obtained in the past 5 years. However, for the discovery of further putative virulence determinants, more sensitive and targeted proteomic methods have to be applied. Here, we review the recent proteome data generated for A. fumigatus and C. albicans that are related to factors required for pathogenicity. Copyright © 2011 Elsevier GmbH. All rights reserved.

  18. The antagonistic effect of Saccharomyces boulardii on Candida albicans filamentation, adhesion and biofilm formation.

    Science.gov (United States)

    Krasowska, Anna; Murzyn, Anna; Dyjankiewicz, Agnieszka; Łukaszewicz, Marcin; Dziadkowiec, Dorota

    2009-12-01

    The dimorphic fungus Candida albicans is a member of the normal flora residing in the intestinal tract of humans. In spite of this, under certain conditions it can induce both superficial and serious systemic diseases, as well as be the cause of gastrointestinal infections. Saccharomyces boulardii is a yeast strain that has been shown to have applications in the prevention and treatment of intestinal infections caused by bacterial pathogens. The purpose of this study was to determine whether S. boulardii affects the virulence factors of C. albicans. We demonstrate the inhibitory effect of live S. boulardii cells on the filamentation (hyphae and pseudohyphae formation) of C. albicans SC5314 strain proportional to the amount of S. boulardii added. An extract from S. boulardii culture has a similar effect. Live S. boulardii and the extract from S. boulardii culture filtrate diminish C. albicans adhesion to and subsequent biofilm formation on polystyrene surfaces under both aerobic and microaerophilic conditions. This effect is very strong and requires lower doses of S. boulardii cells or concentrations of the extract than serum-induced filamentation tests. Saccharomyces boulardii has a strong negative effect on very important virulence factors of C. albicans, i.e. the ability to form filaments and to adhere and form biofilms on plastic surfaces.

  19. The PHR Family: The Role of Extracellular Transglycosylases in Shaping Candida albicans Cells

    Directory of Open Access Journals (Sweden)

    Laura Popolo

    2017-10-01

    Full Text Available Candida albicans is an opportunistic microorganism that can become a pathogen causing mild superficial mycosis or more severe invasive infections that can be life-threatening for debilitated patients. In the etiology of invasive infections, key factors are the adaptability of C. albicans to the different niches of the human body and the transition from a yeast form to hypha. Hyphal morphology confers high adhesiveness to the host cells, as well as the ability to penetrate into organs. The cell wall plays a crucial role in the morphological changes C. albicans undergoes in response to specific environmental cues. Among the different categories of enzymes involved in the formation of the fungal cell wall, the GH72 family of transglycosylases plays an important assembly role. These enzymes cut and religate β-(1,3-glucan, the major determinant of cell shape. In C. albicans, the PHR family encodes GH72 enzymes, some of which work in specific environmental conditions. In this review, we will summarize the work from the initial discovery of PHR genes to the study of the pH-dependent expression of PHR1 and PHR2, from the characterization of the gene products to the recent findings concerning the stress response generated by the lack of GH72 activity in C. albicans hyphae.

  20. An unusual double fungal infection of the bladder due to Candida ...

    African Journals Online (AJOL)

    G.V. KandaSwamy

    rarely pathogenic to humans, but may cause skin lesions, keratitis, onychomycosis, sinusitis and pulmonary infections [2]. Candida infection is synonymous with fungal cystitis, but cladosporium involving the bladder has virtually been unheard of. Case report. A 37-year-old diabetic female, mother of one child, presented with ...

  1. Deficiency of double-strand DNA break repair does not impair Mycobacterium tuberculosis virulence in multiple animal models of infection.

    Science.gov (United States)

    Heaton, Brook E; Barkan, Daniel; Bongiorno, Paola; Karakousis, Petros C; Glickman, Michael S

    2014-08-01

    Mycobacterium tuberculosis persistence within its human host requires mechanisms to resist the effector molecules of host immunity, which exert their bactericidal effects through damaging pathogen proteins, membranes, and DNA. Substantial evidence indicates that bacterial pathogens, including M. tuberculosis, require DNA repair systems to repair the DNA damage inflicted by the host during infection, but the role of double-strand DNA break (DSB) repair systems is unclear. Double-strand DNA breaks are the most cytotoxic form of DNA damage and must be repaired for chromosome replication to proceed. M. tuberculosis elaborates three genetically distinct DSB repair systems: homologous recombination (HR), nonhomologous end joining (NHEJ), and single-strand annealing (SSA). NHEJ, which repairs DSBs in quiescent cells, may be particularly relevant to M. tuberculosis latency. However, very little information is available about the phenotype of DSB repair-deficient M. tuberculosis in animal models of infection. Here we tested M. tuberculosis strains lacking NHEJ (a Δku ΔligD strain), HR (a ΔrecA strain), or both (a ΔrecA Δku strain) in C57BL/6J mice, C3HeB/FeJ mice, guinea pigs, and a mouse hollow-fiber model of infection. We found no difference in bacterial load, histopathology, or host mortality between wild-type and DSB repair mutant strains in any model of infection. These results suggest that the animal models tested do not inflict DSBs on the mycobacterial chromosome, that other repair pathways can compensate for the loss of NHEJ and HR, or that DSB repair is not required for M. tuberculosis pathogenesis. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  2. The effect of ultraviolet radiation on the pathogenesis of Candida albicans in mice

    International Nuclear Information System (INIS)

    Denkins, Y.M.

    1991-01-01

    This dissertation addresses questions concerning the effects of UV radiation on the pathogenesis of opportunistic fungal pathogens such as Candida albicans. UV radiation decreased the survival of Candida-infected mice; however, no correlation was found between suppression of the delayed type hypersensitivity (DTH) response and the course of lethal infection. This suggested that DTH was not protective against lethal disease with this organism. UV radiation also changed the persistence of the organism in the internal organs. UV-irradiated, infected animals had increased numbers of Candida in their kidneys compared to non-irradiated mice. Sensitization prior to UV irradiation aided clearance of the organism from the kidneys of UV-irradiated mice. These data show that UV radiation suppresses cell-mediated immunity to Candida albicans in mice and increases mortality of Candida-infected mice. Moreover, the data suggest that an increase in environmental UV radiation could increase the severity of pathogenic infections

  3. Candida albicans isolated from urine: Phenotypic and molecular identification, virulence factors and antifungal susceptibility

    Directory of Open Access Journals (Sweden)

    Laura Wiebusch

    2017-07-01

    Conclusions: C. albicans isolates from urine have a high capacity for virulence and can be associated with infectious processes. Furthermore, the high percentage of isolates resistant to itraconazole is important because this antifungal agent is commonly used to treat fungal infections in the hospital environment.

  4. The functions of Mediator in Candida albicans support a role in shaping species-specific gene expression.

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    Nathalie Uwamahoro

    Full Text Available The Mediator complex is an essential co-regulator of RNA polymerase II that is conserved throughout eukaryotes. Here we present the first study of Mediator in the pathogenic fungus Candida albicans. We focused on the Middle domain subunit Med31, the Head domain subunit Med20, and Srb9/Med13 from the Kinase domain. The C. albicans Mediator shares some roles with model yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe, such as functions in the response to certain stresses and the role of Med31 in the expression of genes regulated by the activator Ace2. The C. albicans Mediator also has additional roles in the transcription of genes associated with virulence, for example genes related to morphogenesis and gene families enriched in pathogens, such as the ALS adhesins. Consistently, Med31, Med20, and Srb9/Med13 contribute to key virulence attributes of C. albicans, filamentation, and biofilm formation; and ALS1 is a biologically relevant target of Med31 for development of biofilms. Furthermore, Med31 affects virulence of C. albicans in the worm infection model. We present evidence that the roles of Med31 and Srb9/Med13 in the expression of the genes encoding cell wall adhesins are different between S. cerevisiae and C. albicans: they are repressors of the FLO genes in S. cerevisiae and are activators of the ALS genes in C. albicans. This suggests that Mediator subunits regulate adhesion in a distinct manner between these two distantly related fungal species.

  5. A versatile overexpression strategy in the pathogenic yeast Candida albicans: identification of regulators of morphogenesis and fitness.

    Directory of Open Access Journals (Sweden)

    Murielle Chauvel

    Full Text Available Candida albicans is the most frequently encountered human fungal pathogen, causing both superficial infections and life-threatening systemic diseases. Functional genomic studies performed in this organism have mainly used knock-out mutants and extensive collections of overexpression mutants are still lacking. Here, we report the development of a first generation C. albicans ORFeome, the improvement of overexpression systems and the construction of two new libraries of C. albicans strains overexpressing genes for components of signaling networks, in particular protein kinases, protein phosphatases and transcription factors. As a proof of concept, we screened these collections for genes whose overexpression impacts morphogenesis or growth rates in C. albicans. Our screens identified genes previously described for their role in these biological processes, demonstrating the functionality of our strategy, as well as genes that have not been previously associated to these processes. This article emphasizes the potential of systematic overexpression strategies to improve our knowledge of regulatory networks in C. albicans. The C. albicans plasmid and strain collections described here are available at the Fungal Genetics Stock Center. Their extension to a genome-wide scale will represent important resources for the C. albicans community.

  6. Exoenzyme activity and possibility identification of Candida dubliniensis among Candida albicans species isolated from vaginal candidiasis.

    Science.gov (United States)

    Jafari, Maryam; Salari, Samira; Pakshir, Keyvan; Zomorodian, Kamiar

    2017-09-01

    Vulvovaginal candidiasis (VVC) or vaginal candidiasis is a common fungal infection of the genitals causing inflammation, irritation, itching, and vaginal discharge. Common yeast infections are caused by the yeast species C. albicans. However, there are other species of Candida such as C. dubliniensis which are considered as the causative agents of this infection. Hydrolytic enzymes such as proteinase and coagulase are known as virulence factors. The aim of this study was the molecular confirmation and differentiation of C. dubliniensis among C. albicans strains isolated from women with vulvovaginal candidiasis by PCR-Restriction Fragment Length Polymorphism (PCR-RFLP) and the evaluation of proteinase and coagulase activities. A total of 100 C. albicans strains isolated from women with vulvovaginal candidiasis referred to Shiraz medical clinics were enrolled in the study. All the isolates were primarily identified by conventional methods. PCR-RFLP method was used for the confirmation and identification of C. albicans and C. dubliniensis. Moreover, in vitro proteinase and coagulase activities of these isolates were evaluated using bovine serum albumin media and classical rabbit plasma tube test. As a result, PCR-RFLP identified 100% of the isolates as C. albicans, and no C. dubliniensis could be identified in this study. 84% of the isolates showed proteinase activity, whereas coagulase activity was only detected in 5% of the isolates. This study reveals that C. dubliniensis plays no role in vaginal candidiasis in Iranian patients. Proteinase production could be an essential virulence factor in C. albicans pathogenicity, but coagulase activity has less potential in this matter. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Difunctional bacteriophage conjugated with photosensitizers for Candida albicans-targeting photodynamic inactivation.

    Science.gov (United States)

    Dong, Shuai; Shi, Hongxi; Zhang, Xintong; Chen, Xi; Cao, Donghui; Mao, Chuanbin; Gao, Xiang; Wang, Li

    2018-01-01

    Candida albicans is the most prevalent fungal pathogen of the human microbiota, causing infections ranging from superficial infections of the skin to life-threatening systemic infections. Due to the increasing occurrence of antibiotic-resistant C. albicans strains, new approaches to control this pathogen are needed. Photodynamic inactivation is an emerging alternative to treat infections based on the interactions between visible light and photosensitisers, in which pheophorbide a (PPA) is a chlorophyll-based photosensitizer that could induce cell death after light irradiation. Due to PPA's phototoxicity and low efficiency, the main challenge is to implement photosensitizer cell targeting and attacking. In this study, PPA was conjugated with JM-phage by EDC/NHS crosslinking. UV-Vis spectra was used to determine the optimum conjugation percentages of PPA and JM-phage complex for photodynamic inactivation. After photodynamic inactivation, the efficacy of PPA-JM-phage was assessed by performing in vitro experiments, such as MTS assay, scanning electron microscopy, measurement of dysfunctional mitochondria, ROS accumulation, S cell arrest and apoptotic pathway. A single-chain variable-fragment phage (JM) with high affinity to MP65 was screened from human single-fold single-chain variable-fragment libraries and designed as a binding target for C. albicans cells. Subsequently, PPa was integrated into JM phage to generate a combined nanoscale material, which was called PPA-JM-phage. After photodynamic inactivation, the growth of C. albicans was inhibited by PPA-JM-phage and apoptosis was observed. Scanning electron microscopy analysis revealed shrinking and rupturing of C. albicans . We also found that depolarization of mitochondrial membrane potential was decreased and intracellular reactive oxygen species levels were elevated significantly in C. albicans inhibited by PPA-JM-phage. Additionally, PPA-JM-phage also lead to S-phase arrest, and metacaspase activation

  8. Surface control of blastospore attachment and ligand-mediated hyphae adhesion of Candida albicans.

    Science.gov (United States)

    Varghese, Nisha; Yang, Sijie; Sejwal, Preeti; Luk, Yan-Yeung

    2013-11-14

    Adhesion on a surface via nonspecific attachment or multiple ligand-receptor interactions is a critical event for fungal infection by Candida albicans. Here, we find that the tri(ethylene glycol)- and d-mannitol-terminated monolayers do not resist the blastospore attachment, but prevent the hyphae adhesion of C. albicans. The hyphae adhesion can be facilitated by tripeptide sequences of arginine-glycine-aspartic acid (RGD) covalently decorated on a background of tri(ethylene glycol)-terminated monolayers. This adhesion mediated by selected ligands is sensitive to the scrambling of peptide sequences, and is inhibited by the presence of cyclic RGD peptides in the solution.

  9. Difunctional bacteriophage conjugated with photosensitizers for Candida albicans-targeting photodynamic inactivation

    Directory of Open Access Journals (Sweden)

    Dong S

    2018-04-01

    Full Text Available Shuai Dong,1,2 Hongxi Shi,1 Xintong Zhang,1,2 Xi Chen,1 Donghui Cao,2 Chuanbin Mao,3,4 Xiang Gao,1 Li Wang1 1Key Laboratory of Molecular Epigenetics of Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University, 2First Hospital of Jilin University, Changchun, Jilin, 3School of Materials Science and Engineering, Zhejiang University, Hangzhou, Zhejiang, China; 4Department of Chemistry and Biochemistry, Stephenson Life Science Research Center, University of Oklahoma, Norman, OK, USA Background: Candida albicans is the most prevalent fungal pathogen of the human microbiota, causing infections ranging from superficial infections of the skin to life-threatening systemic infections. Due to the increasing occurrence of antibiotic-resistant C. albicans strains, new approaches to control this pathogen are needed. Photodynamic inactivation is an emerging alternative to treat infections based on the interactions between visible light and photosensitisers, in which pheophorbide a (PPA is a chlorophyll-based photosensitizer that could induce cell death after light irradiation. Due to PPA’s phototoxicity and low efficiency, the main challenge is to implement photosensitizer cell targeting and attacking. Methods: In this study, PPA was conjugated with JM-phage by EDC/NHS crosslinking. UV-Vis spectra was used to determine the optimum conjugation percentages of PPA and JM-phage complex for photodynamic inactivation. After photodynamic inactivation, the efficacy of PPA-JM-phage was assessed by performing in vitro experiments, such as MTS assay, scanning electron microscopy, measurement of dysfunctional mitochondria, ROS accumulation, S cell arrest and apoptotic pathway.Results: A single-chain variable-fragment phage (JM with high affinity to MP65 was screened from human single-fold single-chain variable-fragment libraries and designed as a binding target for C. albicans cells. Subsequently, PPa was integrated into JM phage to generate

  10. Influência de Lactobacillus rhamnosus na patogenicidade e na expressão de genes de virulência de Candida albicans: estudo in vitro e in vivo

    OpenAIRE

    Ribeiro, Felipe de Camargo [UNESP

    2015-01-01

    The high incidence of candidiasis caused by Candida albicans and the adaptability of this species, as well as resistance to antifungal drive the development of research on alternative therapies to control this infection. The aim of this study was to evaluate the influence of Lactobacillus rhamnosus and products of their metabolism against C. albicans, evaluating the pathogenicity and the expression of genes that regulate the formation of C. albicans biofilms in vitro and in vivo in invertebra...

  11. Enhanced efficacy of sequential administration of Albendazole for the clearance of Wuchereria bancrofti infection: Double blind RCT.

    Science.gov (United States)

    De Britto, R L; Vanamail, P; Sankari, T; Vijayalakshmi, G; Das, L K; Pani, S P

    2015-06-01

    Till today, there is no effective treatment protocol for the complete clearance of Wuchereria bancrofti (W.b) infection that causes secondary lymphoedema. In a double blind randomized control trial (RCT), 146 asymptomatic W. b infected individuals were randomly assigned to one of the four regimens for 12 days, DEC 300 mg + Doxycycline 100 mg coadministration or DEC 300 mg + Albendazole 400 mg co-administration or DEC 300 mg + Albendazole 400 mg sequential administration or control regimen DEC 300 mg and were followed up at 13, 26 and 52 weeks post-treatment for the clearance of infection. At intake, there was no significant variation in mf counts (F(3,137)=0.044; P=0.988) and antigen levels (F(3,137)=1.433; P=0.236) between the regimens. Primary outcome analysis showed that DEC + Albendazole sequential administration has an enhanced efficacy over DEC + Albendazole co-administration (80.6 Vs 64.7%), and this regimen is significantly different when compared to DEC + doxycycline co-administration and control (PAlbendazole sequential administration appears to be a better option for rapid clearance of W. b microfilariae in 13 weeks time. (Clinical trials.gov identifier - NCT02005653).

  12. Oral Immunization Against Candidiasis Using Lactobacillus casei Displaying Enolase 1 from Candida albicans.

    Science.gov (United States)

    Shibasaki, Seiji; Karasaki, Miki; Tafuku, Senji; Aoki, Wataru; Sewaki, Tomomitsu; Ueda, Mitsuyoshi

    2014-01-01

    Candidiasis is a common fungal infection that is prevalent in immunocompromised individuals. In this study, an oral vaccine against Candida albicans was developed by using the molecular display approach. Enolase 1 protein (Eno1p) of C. albicans was expressed on the Lactobacillus casei cell surface by using poly-gamma-glutamic acid synthetase complex A from Bacillus subtilis as an anchoring protein. The Eno1p-displaying L. casei cells were used to immunize mice, which were later challenged with a lethal dose of C. albicans. The data indicated that the vaccine elicited a strong IgG response and increased the survival rate of the vaccinated mice. Furthermore, L. casei acted as a potent adjuvant and induced high antibody titers that were comparable to those induced by strong adjuvants such as the cholera toxin. Overall, the molecular display method can be used to rapidly develop vaccines that can be conveniently administered and require minimal processing.

  13. Single versus double dose praziquantel comparison on efficacy and Schistosoma mansoni re-infection in preschool-age children in Uganda

    DEFF Research Database (Denmark)

    Nalugwa, Allen; Nuwaha, Fred; Tukahebwa, Edridah Muheki

    2015-01-01

    BACKGROUND: Schistosoma mansoni infection is proven to be a major health problem of preschool-age children in sub-Saharan Africa, yet this age category is not part of the schistosomiasis control program. The objective of this study was to compare the impact of single and double dose praziquantel...... (PZQ) treatment on cure rates (CRs), egg reduction rates (ERRs) and re-infection rates 8 months later, in children aged 1-5 years living along Lake Victoria, Uganda. METHODOLOGY/PRINCIPAL FINDINGS: Infected children (n= 1017) were randomized to receive either a single or double dose of PZQ. Initially...... all children were treated with a single standard oral dose 40 mg/kg body weight of PZQ. Two weeks later a second dose was administered to children in the double dose treatment arm. Side effects were monitored at 30 minutes to 24 hours after each treatment. Efficacy in terms of CRs and ERRs for the two...

  14. Antifungal Activity of Lavandula Angustifolia and Quergues Infectoria Extracts in Comparison with Nystatin on Candida Albicans

    Directory of Open Access Journals (Sweden)

    F. Nouri

    2016-07-01

    Full Text Available Introduction & Objective: Nowadays,herbal extracts are used to treat diseases, especially infec-tious ones. Candida albicans is the most common causes of oral opportunistic infections.In this study, antifungal effects of two herbal extracts were evaluated on an oral pathogen i.e. Candida albicans. Materials & Methods: In this descriptive- analytic study, the Department of Prosthodontics, ,Tehran University of Medical Sciences, school of Dentistry the oral samples of 25 patients with denture stomatitis were collected using sterile swabs. Then the isolated candida albicans and standard candida albicans PTCC 5027 were cultured. The antifungal effect was evaluated with disk plate method. Nystatin and methanol were used as positive and negative control groups, respectively. The power of antifungal activity was evaluated with the inhibition zone diameter of each of the extracts. At the end, the data were analyzed by ANOVA and Fried-man statistical tests. Results: Results showed that extracts of Querques infectoria had great antifungal effects. There was not statistically significant difference between nystatine and Querques infectoria extract (P>0.05 however , Querques infectoria was statistically more effective than lavender extract and nystatin showed the highest antifungal activity (P <0.001. Conclusion: This study showed that plant extracts had positive effects on Candida albicans as compared to nystatin. Thus, we hope to find new herbal medicines and compounds to treat candidiasis in the future. (Sci J Hamadan Univ Med Sci 2016; 23 (2:172-178

  15. Susceptibility of Candida albicans Isolated from Blood to Wickerhamomyces anomalous Mycocins.

    Science.gov (United States)

    Paris, Ana Paula; Persel, Cristiane; Serafin, Cleber Fernando; de Cássia Garcia Simão, Rita; Gandra, Rinaldo Ferreira

    2016-12-01

    The occurrence of infections caused by Candida albicans in developed and developing countries and their resistance to some available antifungal drugs have been viewed as causing a great problem to human health worldwide. In order to find new researched molecules, there are some mycoses secreted by yeasts, especially mycocins produced by Wickerhamomyces anomalus with a broad antimicrobial spectrum of activity. Thus, this trial aimed at evaluating mycocins' activity obtained from environmental W. anomalus cell wall compared to thirty C. albicans strains isolated from blood. Mycocins were extracted from cell walls of three W. anomalus strains (WA40, WA45, and WA92). The 400 μg mL -1 concentration of WA40M1, WA45M2, and WA92M3 mycocin extracts showed the following respective activity results: 96.6, 96.6, and 90.0 % C. albicans strains. WA45M2 and WA92M3 mycocin extracts showed some activity in 3.3 % of C. albicans strains at 50 μg mL -1 concentration. Mycocins extracted from cell walls of three W. anomalus strains named as WA40, WA45, and WA92 showed antifungal activity compared to C. albicans and low degree of hemolysis.

  16. Sensitivity of Candida albicans to essential oils: are they an alternative to antifungal agents?

    Science.gov (United States)

    Bona, E; Cantamessa, S; Pavan, M; Novello, G; Massa, N; Rocchetti, A; Berta, G; Gamalero, E

    2016-12-01

    Candida albicans is an important opportunistic pathogen, responsible for the majority of yeast infections in humans. Essential oils, extracted from aromatic plants, are well-known antimicrobial agents, characterized by a broad spectrum of activities, including antifungal properties. The aim of this work was to assess the sensitivity of 30 different vaginal isolated strains of C. albicans to 12 essential oils, compared to the three main used drugs (clotrimazole, fluconazole and itraconazole). Thirty strains of C. albicans were isolated from vaginal swab on CHROMagar ™ Candida. The agar disc diffusion method was employed to determine the sensitivity to the essential oils. The antifungal activity of the essential oils and antifungal drugs (clotrimazole, itraconazole and fluconazole) were investigated using a microdilution method. Transmission and scanning electron microscopy analyses were performed to get a deep inside on cellular damages. Mint, basil, lavender, tea tree oil, winter savory and oregano essential oils inhibited both the growth and the activity of C. albicans more efficiently than clotrimazole. Damages induced by essential oils at the cellular level were stronger than those caused by clotrimazole. Candida albicans is more sensitive to different essential oils compared to the main used drugs. Moreover, the essential oil affected mainly the cell wall and the membranes of the yeast. The results of this work support the research for new alternatives or complementary therapies against vaginal candidiasis. © 2016 The Society for Applied Microbiology.

  17. Phenotypic Analysis and Virulence of Candida albicans LIG4 Mutants

    Science.gov (United States)

    Andaluz, Encarnación; Calderone, Richard; Reyes, Guadalupe; Larriba, Germán

    2001-01-01

    In previous studies, we reported the isolation and preliminary characterization of a DNA ligase-encoding gene of Candida albicans. This gene (LIG4) is the structural and functional homologue of both yeast and human ligase IV, which is involved in nonhomologous end joining (NHEJ) of DNA double-strand breaks. In the present study, we have shown that there are no other LIG4 homologues in C. albicans. In order to study the function of LIG4 in morphogenesis and virulence, we constructed gene deletions. LIG4 transcript levels were reduced in the heterozygote and were completely absent in null strains. Concomitantly, the heterozygote showed a pronounced defect in myceliation, which was slightly greater in the null strain. This was true with several solid and liquid media, such as Spider medium, medium 199, and 2% glucose–1% yeast extract–2% Bacto Peptone, at several pHs. Reintroduction of the wild-type allele into the null mutant partially restored the ability of cells to form hyphae. In agreement with the positive role of LIG4 in morphogenesis, we detected a significant rise in mRNA levels during the morphological transition. LIG4 is not essential for DNA replication or for the repair of DNA damage induced by ionizing radiation or UV light, indicating that these lesions are repaired primarily by homologous recombination. However, our data show that the NHEJ apparatus of C. albicans may control morphogenesis in this diploid organism. In addition, deletion of one or both copies of LIG4 resulted in attenuation of virulence in a murine model of candidiasis. PMID:11119499

  18. Antifungal effects of undecylenic acid on the biofilm formation of Candida albicans.

    Science.gov (United States)

    Shi, Dongmei; Zhao, Yaxin; Yan, Hongxia; Fu, Hongjun; Shen, Yongnian; Lu, Guixia; Mei, Huan; Qiu, Ying; Li, Dongmei; Liu, Weida

    2016-05-01

    Undecylenic acid can effectively control skin fungal infection, but the mechanism of its fungal inhibition is unclear. Hyphal growth of Candida albicans (C. albicans) and biofilm formation have been well recognized as important virulence factors for the initiation of skin infection and late development of disseminated infection. In this study, we seek to investigate antifungal mechanisms of undecylenic acid by evaluating the virulence factors of C. albicans during biofilm formation. We found that undecylenic acid inhibits biofilm formation of C. albicans effectively with optimal concentration above 3 mM. In the presence of this compound, the morphological transition from yeast to filamentous phase is abolished ultimately when the concentration of undecylenic acid is above 4 mM. Meanwhile, the cell surface is crumpled, and cells display an atrophic appearance under scanning electron microscopy even with low concentration of drug treatment. On the other hand, the drug treatment decreases the transcriptions of hydrolytic enzymes such as secreted aspartic protease, lipase, and phospholipase. Hyphal formation related genes, like HWP1, are significantly reduced in transcriptional level in drug-treated biofilm condition as well. The down-regulated profile of these genes leads to a poorly organized biofilm in undecylenic acid treated environment.

  19. Plasticity of Candida albicans Biofilms

    Science.gov (United States)

    Daniels, Karla J.

    2016-01-01

    SUMMARY Candida albicans, the most pervasive fungal pathogen that colonizes humans, forms biofilms that are architecturally complex. They consist of a basal yeast cell polylayer and an upper region of hyphae encapsulated in extracellular matrix. However, biofilms formed in vitro vary as a result of the different conditions employed in models, the methods used to assess biofilm formation, strain differences, and, in a most dramatic fashion, the configuration of the mating type locus (MTL). Therefore, integrating data from different studies can lead to problems of interpretation if such variability is not taken into account. Here we review the conditions and factors that cause biofilm variation, with the goal of engendering awareness that more attention must be paid to the strains employed, the methods used to assess biofilm development, every aspect of the model employed, and the configuration of the MTL locus. We end by posing a set of questions that may be asked in comparing the results of different studies and developing protocols for new ones. This review should engender the notion that not all biofilms are created equal. PMID:27250770

  20. Selection of aptamers for Candida albicans by cell-SELEX

    International Nuclear Information System (INIS)

    Miranda, Alessandra Nunes Duarte

    2017-01-01

    The growing concern with invasive fungal infections, responsible for an alarming mortality rate of immunosuppressed patients and in Intensive Care Units, evidences the need for a fast and specific method for the Candida albicans detection, since this species is identified as one of the main causes of septicemia. Commonly, it is a challenge for clinicians to determine the primary infection foci, the dissemination degree, or whether the site of a particular surgery is involved. Although scintigraphic imaging represents a promising tool for infectious foci detection, it still lacks a methodology for C. albicans diagnosis due to the absence of specific radiotracers for this microorganism. Aptamers are molecules that have almost ideal properties for use as diagnostic radiopharmaceuticals, such as high specificity for their molecular targets, lack of immunogenicity and toxicity, high tissue penetration and rapid blood clearance. Aptamers can also be labeled with different radionuclides. This work aims to obtain aptamers for specific binding to C. albicans cells for future application as a radiopharmaceutical. It was used a variation of the SELEX (Systematic Evolution of Ligands by EXponential Enrichment) technique, termed cell-SELEX, in which cells are the targets for selection. A selection protocol was standardized using a random library of single-stranded oligonucleotides, each containing two fixed regions flanking a sequence of 40 random nucleotides. This library was incubated with C. albicans cells in the presence of competitors. Then, the binding sequences were separated by centrifugation, resuspended and amplified by PCR. The amplification was confirmed by agarose gel electrophoresis. After that, the ligands were purified to obtain a new pool of ssDNA, from which a new incubation was carried out. The selection parameters were gradually modified in order to increase stringency. This cycle was repeated 12 times to allow the selection of sequences with the maximum

  1. Selection of aptamers for Candida albicans by cell-SELEX; Selecao de aptameros para Candida albicans por cell-SELEX

    Energy Technology Data Exchange (ETDEWEB)

    Miranda, Alessandra Nunes Duarte

    2017-07-01

    The growing concern with invasive fungal infections, responsible for an alarming mortality rate of immunosuppressed patients and in Intensive Care Units, evidences the need for a fast and specific method for the Candida albicans detection, since this species is identified as one of the main causes of septicemia. Commonly, it is a challenge for clinicians to determine the primary infection foci, the dissemination degree, or whether the site of a particular surgery is involved. Although scintigraphic imaging represents a promising tool for infectious foci detection, it still lacks a methodology for C. albicans diagnosis due to the absence of specific radiotracers for this microorganism. Aptamers are molecules that have almost ideal properties for use as diagnostic radiopharmaceuticals, such as high specificity for their molecular targets, lack of immunogenicity and toxicity, high tissue penetration and rapid blood clearance. Aptamers can also be labeled with different radionuclides. This work aims to obtain aptamers for specific binding to C. albicans cells for future application as a radiopharmaceutical. It was used a variation of the SELEX (Systematic Evolution of Ligands by EXponential Enrichment) technique, termed cell-SELEX, in which cells are the targets for selection. A selection protocol was standardized using a random library of single-stranded oligonucleotides, each containing two fixed regions flanking a sequence of 40 random nucleotides. This library was incubated with C. albicans cells in the presence of competitors. Then, the binding sequences were separated by centrifugation, resuspended and amplified by PCR. The amplification was confirmed by agarose gel electrophoresis. After that, the ligands were purified to obtain a new pool of ssDNA, from which a new incubation was carried out. The selection parameters were gradually modified in order to increase stringency. This cycle was repeated 12 times to allow the selection of sequences with the maximum

  2. Genetic and phenotypic intra-species variation in Candida albicans.

    Science.gov (United States)

    Hirakawa, Matthew P; Martinez, Diego A; Sakthikumar, Sharadha; Anderson, Matthew Z; Berlin, Aaron; Gujja, Sharvari; Zeng, Qiandong; Zisson, Ethan; Wang, Joshua M; Greenberg, Joshua M; Berman, Judith; Bennett, Richard J; Cuomo, Christina A

    2015-03-01

    Candida albicans is a commensal fungus of the human gastrointestinal tract and a prevalent opportunistic pathogen. To examine diversity within this species, extensive genomic and phenotypic analyses were performed on 21 clinical C. albicans isolates. Genomic variation was evident in the form of polymorphisms, copy number variations, chromosomal inversions, subtelomeric hypervariation, loss of heterozygosity (LOH), and whole or partial chromosome aneuploidies. All 21 strains were diploid, although karyotypic changes were present in eight of the 21 isolates, with multiple strains being trisomic for Chromosome 4 or Chromosome 7. Aneuploid strains exhibited a general fitness defect relative to euploid strains when grown under replete conditions. All strains were also heterozygous, yet multiple, distinct LOH tracts were present in each isolate. Higher overall levels of genome heterozygosity correlated with faster growth rates, consistent with increased overall fitness. Genes with the highest rates of amino acid substitutions included many cell wall proteins, implicating fast evolving changes in cell adhesion and host interactions. One clinical isolate, P94015, presented several striking properties including a novel cellular phenotype, an inability to filament, drug resistance, and decreased virulence. Several of these properties were shown to be due to a homozygous nonsense mutation in the EFG1 gene. Furthermore, loss of EFG1 function resulted in increased fitness of P94015 in a commensal model of infection. Our analysis therefore reveals intra-species genetic and phenotypic differences in C. albicans and delineates a natural mutation that alters the balance between commensalism and pathogenicity. © 2015 Hirakawa et al.; Published by Cold Spring Harbor Laboratory Press.

  3. Lemongrass-Incorporated Tissue Conditioner Against Candida albicans Culture

    Science.gov (United States)

    Amornvit, Pokpong; Srithavaj, Theerathavaj

    2014-01-01

    Background: Tissue conditioner is applied popularly with dental prosthesis during wound healing process but it becomes a reservoir of oral microbiota, especially Candida species after long-term usage. Several antifungal drugs have been mixed with this material to control fungal level. In this study, lemongrass essential oil was added into COE-COMFORT tissue conditioner before being determined for anti-Candida efficacy. Materials and Methods: Lemongrass (Cymbopogon citratus) essential oil was primarily determined for antifungal activity against C. albicans American type culture collection (ATCC) 10231 and MIC (minimum inhibitory concentration) value by agar disk diffusion and broth microdilution methods, respectively. COE-COMFORT tissue conditioner was prepared as recommended by the manufacturer after a fixed volume of the oil at its MIC or higher concentrations were mixed thoroughly in its liquid part. Antifungal efficacy of the tissue conditioner with/without herb was finally analyzed. Results: Lemongrass essential oil displayed potent antifungal activity against C. albicans ATCC 10231and its MIC value was 0.06% (v/v). Dissimilarly, the tissue conditioner containing the oil at MIC level did not cease the growth of the tested fungus. Both reference and clinical isolates of C. albicans were completely inhibited after exposed to the tissue conditioner containing at least 0.25% (v/v) of the oil (approximately 4-time MIC). The tissue conditioner without herb or with nystatin was employed as negative or positive control, respectively. Conclusion: COE-COMFORT tissue conditioner supplemented with lemongrass essential oil obviously demonstrated another desirable property as in vitro anti-Candida efficacy to minimize the risk of getting Candidal infection. PMID:25177638

  4. Rheumatoid arthritis patients exhibit impaired Candida albicans-specific Th17 responses.

    Science.gov (United States)

    Bishu, Shrinivas; Su, Ee Wern; Wilkerson, Erich R; Reckley, Kelly A; Jones, Donald M; McGeachy, Mandy J; Gaffen, Sarah L; Levesque, Marc C

    2014-02-11

    Accumulating data implicate the CD4+ T cell subset (Th17 cells) in rheumatoid arthritis (RA). IL-17 is an inflammatory cytokine that induces tumor necrosis factor (TNF)α, IL-1β and IL-6, all of which are targets of biologic therapies used to treat RA. RA patients are well documented to experience more infections than age-matched controls, and biologic therapies further increase the risk of infection. The Th17/IL-17 axis is vital for immunity to fungi, especially the commensal fungus Candida albicans. Therefore, we were prompted to examine the relationship between RA and susceptibility to C. albicans because of the increasing interest in Th17 cells and IL-17 in driving autoimmunity, and the advent of new biologics that target this pathway. We analyzed peripheral blood and saliva from 48 RA and 33 healthy control subjects. To assess C. albicans-specific Th17 responses, PBMCs were co-cultured with heat-killed C. albicans extract, and IL-17A levels in conditioned supernatants were measured by ELISA. The frequency of Th17 and Th1 cells was determined by flow cytometry. As a measure of IL-17A-mediated effector responses, we evaluated C. albicans colonization rates in the oral cavity, salivary fungicidal activity and levels of the antimicrobial peptide β-defensin 2 (BD2) in saliva. Compared to controls, PBMCs from RA subjects exhibited elevated baseline production of IL-17A (P = 0.004), although they had similar capacity to produce IL-17A in response to Th17 cell differentiating cytokines (P = 0.91). However RA PBMCs secreted less IL-17A in response to C. albicans antigens (P = 0.006). Significantly more RA patients were colonized with C. albicans in the oral cavity than healthy subjects (P = 0.02). Concomitantly, RA saliva had reduced concentrations of salivary BD2 (P = 0.02). Nonetheless, salivary fungicidal activity was preserved in RA subjects (P = 0.70). RA subjects exhibit detectable impairments in oral immune responses to C. albicans, a

  5. Diminished Antimicrobial Peptide and Antifungal Antibiotic Activities against Candida albicans in Denture Adhesive

    Directory of Open Access Journals (Sweden)

    Amber M. Bates

    2017-02-01

    Full Text Available The underlying causes of denture stomatitis may be related to the long-term use of adhesives, which may predispose individuals to oral candidiasis. In this study, we hypothesize that antimicrobial peptides and antifungal antibiotics have diminished anti-Candida activities in denture adhesive. To show this, nine antimicrobial peptides and five antifungal antibiotics with and without 1.0% denture adhesive were incubated with Candida albicans strains ATCC 64124 and HMV4C in radial diffusion assays. In gels with 1.0% adhesive, HNP-1, HBD2, HBD3, IP-10, LL37 (only one strain, histatin 5 (only one strain, lactoferricin B, and SMAP28 showed diminished activity against C. albicans. In gels with 1.0% adhesive, amphotericin B and chlorhexidine dihydrochloride were active against both strains of C. albicans. These results suggest that denture adhesive may inactivate innate immune mediators in the oral cavity increasing the risk of C. albicans infections, but inclusion of antifungal antibiotics to denture adhesive may aid in prevention or treatment of Candida infections and denture stomatitis.

  6. A novel small molecule methyltransferase is important for virulence in Candida albicans.

    Science.gov (United States)

    Lissina, Elena; Weiss, David; Young, Brian; Rella, Antonella; Cheung-Ong, Kahlin; Del Poeta, Maurizio; Clarke, Steven G; Giaever, Guri; Nislow, Corey

    2013-12-20

    Candida albicans is an opportunistic pathogen capable of causing life-threatening infections in immunocompromised individuals. Despite its significant health impact, our understanding of C. albicans pathogenicity is limited, particularly at the molecular level. One of the largely understudied enzyme families in C. albicans are small molecule AdoMet-dependent methyltransferases (smMTases), which are important for maintenance of cellular homeostasis by clearing toxic chemicals, generating novel cellular intermediates, and regulating intra- and interspecies interactions. In this study, we demonstrated that C. albicans Crg1 (CaCrg1) is a bona fide smMTase that interacts with the toxin in vitro and in vivo. We report that CaCrg1 is important for virulence-related processes such as adhesion, hyphal elongation, and membrane trafficking. Biochemical and genetic analyses showed that CaCrg1 plays a role in the complex sphingolipid pathway: it binds to exogenous short-chain ceramides in vitro and interacts genetically with genes of glucosylceramide pathway, and the deletion of CaCRG1 leads to significant changes in the abundance of phytoceramides. Finally we found that this novel lipid-related smMTase is required for virulence in the waxmoth Galleria mellonella, a model of infection.

  7. Determination of germ tube, phospholipase, and proteinase production by bloodstream isolates of Candida albicans

    Directory of Open Access Journals (Sweden)

    Antonella Souza Mattei

    2013-06-01

    Full Text Available Introduction Candida albicans is a commensal and opportunistic agent that causes infection in immunocompromised individuals. Several attributes contribute to the virulence and pathogenicity of this yeast, including the production of germ tubes (GTs and extracellular hydrolytic enzymes, particularly phospholipase and proteinase. This study aimed to investigate GT production and phospholipase and proteinase activities in bloodstream isolates of C. albicans. Methods One hundred fifty-three C. albicans isolates were obtained from blood samples and analyzed for GT, phospholipase, and proteinase production. The assays were performed in duplicate in egg yolk medium containing bovine serum albumin and human serum. Results Detectable amounts of proteinase were produced by 97% of the isolates, and 78% of the isolates produced phospholipase. GTs were produced by 95% of the isolates. A majority of the isolates exhibited low levels of phospholipase production and high levels of proteinase production. Conclusions Bloodstream isolates of C. albicans produce virulence factors such as GT and hydrolytic enzymes that enable them to cause infection under favorable conditions.

  8. Profiling of Candida albicans Gene Expression During Intra-abdominal Candidiasis Identifies Biologic Processes Involved in Pathogenesis

    Science.gov (United States)

    Cheng, Shaoji; Clancy, Cornelius J.; Xu, Wenjie; Schneider, Frank; Hao, Binghua; Mitchell, Aaron P.; Nguyen, M. Hong

    2013-01-01

    Background. The pathogenesis of intra-abdominal candidiasis is poorly understood. Methods. Mice were intraperitoneally infected with Candida albicans (1 × 106 colony-forming units) and sterile stool. nanoString assays were used to quantitate messenger RNA for 145 C. albicans genes within the peritoneal cavity at 48 hours. Results. Within 6 hours after infection, mice developed peritonitis, characterized by high yeast burdens, neutrophil influx, and a pH of 7.9 within peritoneal fluid. Organ invasion by hyphae and early abscess formation were evident 6 and 24 hours after infection, respectively; abscesses resolved by day 14. nanoString assays revealed adhesion and responses to alkaline pH, osmolarity, and stress as biologic processes activated in the peritoneal cavity. Disruption of the highly-expressed gene RIM101, which encodes an alkaline-regulated transcription factor, did not impact cellular morphology but reduced both C. albicans burden during early peritonitis and C. albicans persistence within abscesses. RIM101 influenced expression of 49 genes during intra-abdominal candidiasis, including previously unidentified Rim101 targets. Overexpression of the RIM101-dependent gene SAP5, which encodes a secreted protease, restored the ability of a rim101 mutant to persist within abscesses. Conclusions. A mouse model of intra-abdominal candidiasis is valuable for studying pathogenesis and C. albicans gene expression. RIM101 contributes to persistence within intra-abdominal abscesses, at least in part through activation of SAP5. PMID:24006479

  9. Effects of influenza plus pneumococcal conjugate vaccination versus influenza vaccination alone in preventing respiratory tract infections in children : a randomized, double-blind, placebo-controlled trial

    NARCIS (Netherlands)

    Jansen, Angelique G S C; Sanders, Elisabeth A M; Hoes, Arno W; van Loon, Anton M; Hak, Eelko

    2008-01-01

    OBJECTIVE: To evaluate the effects of influenza vaccination with or without heptavalent pneumococcal conjugate vaccination on respiratory tract infections (RTIs) in children. STUDY DESIGN: This was a randomized, double-blind, placebo-controlled trial comprising 579 children age 18 to 72 months with

  10. Single-dose fluconazole versus standard 2-week therapy for oropharyngeal candidiasis in HIV-infected patients: a randomized, double-blind, double-dummy trial.

    NARCIS (Netherlands)

    Hamza, O.J.M.; Matee, M.I.N.; Bruggemann, R.J.M.; Moshi, M.J.; Simon, E.N.; Mugusi, F.; Mikx, F.H.M.; Lee, H.A.L. van der; Verweij, P.E.; Ven, A.J.A.M. van der

    2008-01-01

    BACKGROUND: Oropharyngeal candidiasis is the most common opportunistic infection affecting patients with human immunodeficiency virus (HIV) infection. Because of convenience, cost, and reluctance to complicate antiretroviral treatment regimens, single-dose fluconazole may be a favorable regimen for

  11. Effects of nanosecond pulsed electric fields (nsPEFs) on the human fungal pathogen Candida albicans: an in vitro study

    Science.gov (United States)

    Guo, Jinsong; Dang, Jie; Wang, Kaile; Zhang, Jue; Fang, Jing

    2018-05-01

    Candida albicans is the leading human fungal pathogen that causes many life-threatening infections. Notably, the current clinical trial data indicate that Candida species shows the emerging resistance to anti-fungal drugs. The aim of this study was to evaluate the antifungal effects of nanosecond pulsed electric fields (nsPEFs) as a novel drug-free strategy in vitro. In this study, we investigated the inactivation and permeabilization effects of C. albicans under different nsPEFs exposure conditions (100 pulses, 100 ns in duration, intensities of 20, 40 kV cm‑1). Cell death was studied by annexin-V and propidium iodide staining. The changes of intracellular Ca2+ concentration after nsPEFs treatment were observed using Fluo-4 AM. Results show that C. albicans cells and biofilms were both obviously inhibited and destroyed after nsPEFs treatment. Furthermore, C. albicans cells were significantly permeabilized after nsPEFs treatment. Additionally, nsPEFs exposure led to a large amount of DNA and protein leakage. Importantly, nsPEFs induced a field strength-dependent apoptosis in C. albicans cells. Further experiments revealed that Ca2+ involved in nsPEFs induced C. albicans apoptosis. In conclusion, this proof-of-concept study provides a potential alternative drug-free strategy for killing pathogenic Candida species.

  12. Binding of Candida albicans to Human CEACAM1 and CEACAM6 Modulates the Inflammatory Response of Intestinal Epithelial Cells

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    Esther Klaile

    2017-03-01

    Full Text Available Candida albicans colonizes human mucosa, including the gastrointestinal tract, as a commensal. In immunocompromised patients, C. albicans can breach the intestinal epithelial barrier and cause fatal invasive infections. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1; CD66a, CEACAM5 (CEA, and CEACAM6 (CD66c are immunomodulatory receptors expressed on human mucosa and are recruited by bacterial and viral pathogens. Here we show for the first time that a fungal pathogen (i.e., C. albicans also binds directly to the extracellular domain of human CEACAM1, CEACAM3, CEACAM5, and CEACAM6. Binding was specific for human CEACAMs and mediated by the N-terminal IgV-like domain. In enterocytic C2BBe1 cells, C. albicans caused a transient tyrosine phosphorylation of CEACAM1 and induced higher expression of membrane-bound CEACAM1 and soluble CEACAM6. Lack of the CEACAM1 receptor after short hairpin RNA (shRNA knockdown abolished CXCL8 (interleukin-8 secretion by C2BBe1 cells in response to C. albicans. In CEACAM1-competent cells, the addition of recombinant soluble CEACAM6 reduced the C. albicans-induced CXCL8 secretion.

  13. In vitro activity of xanthorrhizol isolated from the rhizome of Javanese turmeric (Curcuma xanthorrhiza Roxb.) against Candida albicans biofilms.

    Science.gov (United States)

    Rukayadi, Yaya; Hwang, Jae-Kwan

    2013-07-01

    The purpose of this study was to investigate the activity of xanthorrhizol isolated from Curcuma xanthorrhiza Roxb. on Candida albicans biofilms at adherent, intermediate, and mature phase of growth. C. albicans biofilms were formed in flat-bottom 96-well microtiter plates. The biofilms of C. albicans at different phases of development were exposed to xanthorrhizol at different concentrations (0.5 µg/mL-256 µg/mL) for 24 h. The metabolic activity of cells within the biofilms was quantified using the XTT reduction assay. Sessile minimum inhibitory concentrations (SMICs) were determined at 50% and 80% reduction in the biofilm OD₄₉₀ compared to the control wells. The SMIC₅₀ and SMIC₈₀ of xanthorrhizol against 18 C. albicans biofilms were 4--16 µg/mL and 8--32 µg/mL, respectively. The results demonstrated that the activity of xanthorrhizol in reducing C. albicans biofilms OD₄₉₀ was dependent on the concentration and the phase of growth of biofilm. Xanthorrhizol at concentration of 8 µg/mL completely reduced in biofilm referring to XTT-colorimetric readings at adherent phase, whereas 32 µg/mL of xanthorrhizol reduced 87.95% and 67.48 % of biofilm referring to XTT-colorimetric readings at intermediate and mature phases, respectively. Xanthorrhizol displayed potent activity against C. albicans biofilms in vitro and therefore might have potential therapeutic implication for biofilm-associated candidal infections. Copyright © 2012 John Wiley & Sons, Ltd.

  14. Lactobacillus rhamnosus inhibits Candida albicans virulence factors in vitro and modulates immune system in Galleria mellonella.

    Science.gov (United States)

    Ribeiro, F C; de Barros, P P; Rossoni, R D; Junqueira, J C; Jorge, A O C

    2017-01-01

    The aim of this study was to evaluate the potential anti-Candida effects of Lactobacillus rhamnosus ATCC 9595 on Candida albicans ATCC 18804 using in vitro and in vivo models. The in vitro analysis evaluated the effects of L. rhamnosus on C. albicans's biofilm formation by CFU count and metabolic activity, filamentation capacity, and adhesion (ALS3 and HWP1) and transcriptional regulatory gene (BCR1 and CPH1) expression. The in vitro results showed that both the L. rhamnosus cells and supernatant reduced C. albicans biofilm formation, filamentation and gene expression. In the in vivo study, the treatment with L. rhamnosus supernatant increased 80% the survival of Galleria mellonella larvae infected with C. albicans. Furthermore, the supernatant of L. rhamnosus recruited haemocytes into the haemolymph (2·1-fold increase). Lactobacillus rhamnosus reduced the biofilm formation and filamentation of C. albicans in vitro by negatively regulating all studied C. albicans genes. Lactobacillus rhamnosus protected G. mellonella against experimental candidiasis in vivo. This study is the first study to report the anti-Candida properties of L. rhamnosus ATCC 9595. The supernatant of this strain has immunomodulatory effects on the G. mellonella model and protects the larvae against pathogens. © 2016 The Society for Applied Microbiology.

  15. Use of multilocus sequence typing for the investigation of colonisation by Candida albicans in intensive care unit patients.

    Science.gov (United States)

    Cliff, P R; Sandoe, J A T; Heritage, J; Barton, R C

    2008-05-01

    A prospective study was performed to determine the prevalence of candidal colonisation on the general intensive care unit at a large teaching hospital. Colonisation with Candida spp. was found to be common, occurring in 79% of patients on the unit. C. albicans was the commonest species, colonising 64% of patients, followed by C. glabrata (18%) and C. parapsilosis (14%). Most of the members of staff tested carried Candida spp. at some point, although carriage appeared to be transient. C. parapsilosis was the most commonly isolated species from staff hands, whereas C. albicans was the most commonly isolated species from the mouth. The molecular epidemiology of C. albicans was investigated using Ca3 typing and multilocus sequence typing (MLST). MLST proved to be a reproducible typing method and a useful tool for the investigation of the molecular epidemiology of C. albicans. The results of the molecular typing provided evidence for the presence of an endemic strain on the unit, which was isolated repeatedly from patients and staff. This finding suggests horizontal transmission of C. albicans on the unit though it may also reflect the relative frequency of C. albicans strain types colonising patients on admission. This study has important implications for the epidemiology of systemic candidal infections.

  16. Double whammy- acute splenic sequestration crisis in patient with aplastic crisis due to acute parvovirus infection.

    Science.gov (United States)

    Minhas, Parminder S; K Virdi, Jaspreet; Patel, Rajeshkumar

    2017-07-01

    Splenic dysfunction is a major feature of sickle cell disease (SCD) and can manifest as acute splenic sequestration crisis (ASSC), which is the earliest life-threatening complication seen in patients with SCD. Aplastic crisis is another potentially deadly complication of sickle cell disease that develops when erythrocyte production temporarily drops. Infection with parvovirus B-19 frequently causes aplastic crises. These two complications are known to be mutually exclusive due to their classic presentation signs and symptoms but there have been few cases where a patient can have concomitant presentation of both phenomena, which can result in a fatal outcome. These few cases force us to rethink the etiology and subsequent management guidelines of these complications. We present to you a case of an unfortunate 23-year-old female who had both complications occurring at the same time, resulting in death.

  17. Double blow: Alien crayfish infected with invasive temnocephalan in South African waters

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    Louis du Preez

    2013-09-01

    Full Text Available Trade in live, freshwater crayfish for ornamental markets, as well as for aquaculture, has grown rapidly and has become the major pathway for the introduction of non-indigenous crayfish species to several countries worldwide. Here we report on the first record of the Australian "redclaw" Cherax quadracarinatus in the natural waters of a game reserve in South Africa. To compound the situation, these redclaw crayfish were infected with a non-indigenous temnocephalan flatworm parasite. Both crayfish and temnocephalan were in full breeding condition, with young. Further spreading of this crayfish to the subtropical, water-rich, northern KwaZulu-Natal Province of South Africa and southern Mozambique is predicted. Not only might the crayfish compete with indigenous aquatic invertebrates but the non-host-specific temnocephalan might transfer to local decapods, such as freshwater crabs.

  18. Biofilm extracellular DNA enhances mixed species biofilms of Staphylococcus epidermidis and Candida albicans.

    Science.gov (United States)

    Pammi, Mohan; Liang, Rong; Hicks, John; Mistretta, Toni-Ann; Versalovic, James

    2013-11-14

    Polymicrobial infections are responsible for significant mortality and morbidity in adults and children. Staphylococcus epidermidis and Candida albicans are the most frequent combination of organisms isolated from polymicrobial infections. Vascular indwelling catheters are sites for mixed species biofilm formation and pose a significant risk for polymicrobial infections. We hypothesized that enhancement of biofilms in a mixed species environment increases patient mortality and morbidity. Mixed species biofilms of S. epidermidis and C. albicans were evaluated in vitro and in a subcutaneous catheter infection model in vivo. Mixed species biofilms were enhanced compared to single species biofilms of either S. epidermidis or C. albicans. A mixed species environment increased catheter infection and increased dissemination of S. epidermidis in mice. Microarrays were used to explore differential gene expression of S. epidermidis in the mixed species biofilms. In mixed species biofilms, compared to single species S. epidermidis biofilms, 2.7% of S. epidermidis genes were upregulated and 6% were down regulated. Staphylococcal autolysis repressors lrgA and lrgB were down regulated 36-fold and 27-fold respectively. The role of biofilm extracellular DNA was investigated by quantitation and by evaluating the effects of DNAse in a concentration and time dependent manner. S. epidermidis specific eDNA was increased in mixed species biofilms and further confirmed by degradation with DNAse. Mixed-species biofilms are enhanced and associated with increased S. epidermidis-specific eDNA in vitro and greater systemic dissemination of S. epidermidis in vivo. Down regulation of the lrg operon, a repressor of autolysis, associated with increased eDNA suggests a possible role for bacterial autolysis in mixed species biofilms. Enhancement and systemic dissemination of S. epidermidis may explain adverse outcomes after clinical polymicrobial infections of S. epidermidis and C. albicans.

  19. Biofilm extracellular DNA enhances mixed species biofilms of Staphylococcus epidermidis and Candida albicans

    Science.gov (United States)

    2013-01-01

    Background Polymicrobial infections are responsible for significant mortality and morbidity in adults and children. Staphylococcus epidermidis and Candida albicans are the most frequent combination of organisms isolated from polymicrobial infections. Vascular indwelling catheters are sites for mixed species biofilm formation and pose a significant risk for polymicrobial infections. We hypothesized that enhancement of biofilms in a mixed species environment increases patient mortality and morbidity. Results Mixed species biofilms of S. epidermidis and C. albicans were evaluated in vitro and in a subcutaneous catheter infection model in vivo. Mixed species biofilms were enhanced compared to single species biofilms of either S. epidermidis or C. albicans. A mixed species environment increased catheter infection and increased dissemination of S. epidermidis in mice. Microarrays were used to explore differential gene expression of S. epidermidis in the mixed species biofilms. In mixed species biofilms, compared to single species S. epidermidis biofilms, 2.7% of S. epidermidis genes were upregulated and 6% were down regulated. Staphylococcal autolysis repressors lrgA and lrgB were down regulated 36-fold and 27-fold respectively. The role of biofilm extracellular DNA was investigated by quantitation and by evaluating the effects of DNAse in a concentration and time dependent manner. S. epidermidis specific eDNA was increased in mixed species biofilms and further confirmed by degradation with DNAse. Conclusions Mixed-species biofilms are enhanced and associated with increased S. epidermidis-specific eDNA in vitro and greater systemic dissemination of S. epidermidis in vivo. Down regulation of the lrg operon, a repressor of autolysis, associated with increased eDNA suggests a possible role for bacterial autolysis in mixed species biofilms. Enhancement and systemic dissemination of S. epidermidis may explain adverse outcomes after clinical polymicrobial infections of S

  20. Fluconazole induces rapid high-frequency MTL homozygosis with microbiological polymorphism in Candida albicans

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    Tsong-Yih Ou

    2017-12-01

    Full Text Available Background: Candida albicans, a common fungal pathogen that can cause opportunistic infections, is regarded as an apparently asexual, diploid fungus. A parasexual cycle was previously found between homozygotes with opposite mating type-like loci (MTLa/α. Fluconazole-resistant strains had a higher proportion of MTL homozygotes, whereas MTL homozygous C. albicans was found in only about 3.2% of clinical strains. MTL heterozygotes had a low frequency (1.4 × 10−4 of white–opaque switching to MTL homozygotes in nature. Methods: Here, a reference C. albicans strain (SC5314 was used in a fluconazole-induced assay to obtain standard opaque MTL homozygous strains and first-generation daughter strains from the fluconazole inhibition zone. Further separation methods were employed to produce second- and third-generation daughter strains. Polymerase chain reaction analysis based on MTL genes was used to define MTL genotypes, and microscopic observations, a flow-cytometric assay, and an antifungal E-test were used to compare microbiological characteristics. Results: MTL homozygotes were found at a high frequency (17 of 35; 48.6% in fluconazole-induced first-generation daughter strains, as were morphological polymorphisms, decreased DNA content, and modified antifungal drug susceptibility. High-frequency MTL homozygosity was identified inside the fluconazole inhibition zone within 24 hours. The DNA content of fluconazole-induced daughter strains was reduced compared with their progenitor SC5314 and standard MTL homozygous strains. Conclusion: Treatment with fluconazole, commonly used to treat invasive candidiasis, inhibited the growth of C. albicans and altered its microbiological characteristics. Our results suggest that fluconazole treatment induces the high frequency of loss of heterozygosity and microbiological polymorphism in C. albicans. Keywords: Candida albicans, fluconazole, loss of heterozygosity, mating type-like gene

  1. Horizontal transmission of Candida albicans and evidence of a vaccine response in mice colonized with the fungus.

    Science.gov (United States)

    Cutler, Jim E; Corti, Miriam; Lambert, Patrick; Ferris, Michael; Xin, Hong

    2011-01-01

    Disseminated candidiasis is the third leading nosocomial blood stream infection in the United States and is often fatal. We previously showed that disseminated candidiasis was preventable in normal mice by immunization with either a glycopeptide or a peptide synthetic vaccine, both of which were Candida albicans cell wall derived. A weakness of these studies is that, unlike humans, mice do not have a C. albicans GI flora and they lack Candida serum antibodies. We examined the influence of C. albicans GI tract colonization and serum antibodies on mouse vaccination responses to the peptide, Fba, derived from fructose bisphosphate aldolase which has cytosolic and cell wall distributions in the fungus. We evaluated the effect of live C. albicans in drinking water and antimicrobial agents on establishment of Candida colonization of the mouse GI tract. Body mass, C. albicans in feces, and fungal-specific serum antibodies were monitored longitudinally. Unexpectedly, C. albicans colonization occurred in mice that received only antibiotics in their drinking water, provided that the mice were housed in the same room as intentionally colonized mice. The fungal strain in unintentionally colonized mice appeared identical to the strain used for intentional GI-tract colonization. This is the first report of horizontal transmission and spontaneous C. albicans colonization in mice. Importantly, many Candida-colonized mice developed serum fungal-specific antibodies. Despite the GI-tract colonization and presence of serum antibodies, the animals made antibodies in response to the Fba immunogen. This mouse model has potential for elucidating C. albicans horizontal transmission and for exploring factors that induce host defense against disseminated candidiasis. Furthermore, a combined protracted GI-tract colonization with Candida and the possibility of serum antibody responses to the presence of the fungus makes this an attractive mouse model for testing the efficacy of vaccines

  2. Horizontal transmission of Candida albicans and evidence of a vaccine response in mice colonized with the fungus.

    Directory of Open Access Journals (Sweden)

    Jim E Cutler

    Full Text Available Disseminated candidiasis is the third leading nosocomial blood stream infection in the United States and is often fatal. We previously showed that disseminated candidiasis was preventable in normal mice by immunization with either a glycopeptide or a peptide synthetic vaccine, both of which were Candida albicans cell wall derived. A weakness of these studies is that, unlike humans, mice do not have a C. albicans GI flora and they lack Candida serum antibodies. We examined the influence of C. albicans GI tract colonization and serum antibodies on mouse vaccination responses to the peptide, Fba, derived from fructose bisphosphate aldolase which has cytosolic and cell wall distributions in the fungus. We evaluated the effect of live C. albicans in drinking water and antimicrobial agents on establishment of Candida colonization of the mouse GI tract. Body mass, C. albicans in feces, and fungal-specific serum antibodies were monitored longitudinally. Unexpectedly, C. albicans colonization occurred in mice that received only antibiotics in their drinking water, provided that the mice were housed in the same room as intentionally colonized mice. The fungal strain in unintentionally colonized mice appeared identical to the strain used for intentional GI-tract colonization. This is the first report of horizontal transmission and spontaneous C. albicans colonization in mice. Importantly, many Candida-colonized mice developed serum fungal-specific antibodies. Despite the GI-tract colonization and presence of serum antibodies, the animals made antibodies in response to the Fba immunogen. This mouse model has potential for elucidating C. albicans horizontal transmission and for exploring factors that induce host defense against disseminated candidiasis. Furthermore, a combined protracted GI-tract colonization with Candida and the possibility of serum antibody responses to the presence of the fungus makes this an attractive mouse model for testing the

  3. Candida albicans biofilm development in vitro for photodynamic therapy study

    International Nuclear Information System (INIS)

    Suzuki, Luis Claudio

    2009-01-01

    Photodynamic therapy (PDT) is a phototherapy based on the use of a photo sensitizer (PS) in the presence of low intensity light with resonant wavelength of absorption of the PS and biological systems that can raise awareness, generating reactive oxygen species. Studies show that PDT has a lethal effect on Candida albicans. The biofilm formed by C. albicans is the cause of infections associated with medical devices such as catheters, with a proven resistance to antifungal agents, and the removal of the catheter colonized almost always is necessary. However, few studies in literature report the behavior and response of biofilm organized by C. albicans against PDT. The aims of this study were to develop a methodology for in vitro biofilm formation of C. albicans, evaluate the sensitivity of the biofilm of C. albicans to antimicrobial photodynamic therapy using PS as the methylene blue (MB) and hypocrellin B: La +3 (HBL a+3 ) and analyze the biofilm by Optical Coherence Tomography (OCT). For biofilm formation, discs were made from elastomeric silicone catheters. The PS were dissolved in solution of PBS, and the MB had two different concentrations tested in the biofilm: 100μM and 1mM; HBLa +3 only one of 10μM. The irradiation of both dyes with the microorganism was done by two different LEDs, one with red emission at λ = 630nm ± 20nm and the other one blue emission at λ = 460nm ± 30nm. We performed a curve of survival fraction versus time of irradiation of each sample with biofilm and suspension of the microorganism in the yeast form to verify the susceptibility of the front PDT. The yeast showed 100% reduction using both PS, but at different times of irradiation (30s to HBLa +3 and 6 min for the MB at 100μM). When the therapy was applied in biofilm, the MB 100μM did not show any significant reduction, while at concentration of 1mM was reduced by 100% after 6 min of irradiation. The HBLa +3 biofilm group showed a lower reduction in the concentration of 10μM in

  4. Early double-negative thymocyte export in Trypanosoma cruzi infection is restricted by sphingosine receptors and associated with human chagas disease.

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    Ailin Lepletier

    2014-10-01

    Full Text Available The protozoan parasite Trypanosoma cruzi is able to target the thymus and induce alterations of the thymic microenvironmental and lymphoid compartments. Acute infection results in severe atrophy of the organ and early release of immature thymocytes into the periphery. To date, the pathophysiological effects of thymic changes promoted by parasite-inducing premature release of thymocytes to the periphery has remained elusive. Herein, we show that sphingosine-1-phosphate (S1P, a potent mediator of T cell chemotaxis, plays a role in the exit of immature double-negative thymocytes in experimental Chagas disease. In thymuses from T. cruzi-infected mice we detected reduced transcription of the S1P kinase 1 and 2 genes related to S1P biosynthesis, together with increased transcription of the SGPL1 sphingosine-1-lyase gene, whose product inactivates S1P. These changes were associated with reduced intrathymic levels of S1P kinase activity. Interestingly, double-negative thymocytes from infected animals expressed high levels of the S1P receptor during infection, and migrated to lower levels of S1P. Moreover, during T. cruzi infection, this thymocyte subset expresses high levels of IL-17 and TNF-α cytokines upon polyclonal stimulation. In vivo treatment with the S1P receptor antagonist FTY720 resulted in recovery the numbers of double-negative thymocytes in infected thymuses to physiological levels. Finally, we showed increased numbers of double-negative T cells in the peripheral blood in severe cardiac forms of human Chagas disease.

  5. Cranberry-derived proanthocyanidins prevent formation of Candida albicans biofilms in artificial urine through biofilm- and adherence-specific mechanisms.

    Science.gov (United States)

    Rane, Hallie S; Bernardo, Stella M; Howell, Amy B; Lee, Samuel A

    2014-02-01

    Candida albicans is a common cause of nosocomial urinary tract infections (UTIs) and is responsible for increased morbidity and healthcare costs. Moreover, the US Centers for Medicare & Medicaid Services no longer reimburse for hospital-acquired catheter-associated UTIs. Thus, development of specific approaches for the prevention of Candida urinary infections is needed. Cranberry juice-derived proanthocyanidins (PACs) have efficacy in the prevention of bacterial UTIs, partially due to anti-adherence properties, but there are limited data on their use for the prevention and/or treatment of Candida UTIs. Therefore, we sought to systematically assess the in vitro effect of cranberry-derived PACs on C. albicans biofilm formation in artificial urine. C. albicans biofilms in artificial urine were coincubated with cranberry PACs at serially increasing concentrations and biofilm metabolic activity was assessed using the XTT assay in static microplate and silicone disc models. Cranberry PAC concentrations of ≥16 mg/L significantly reduced biofilm formation in all C. albicans strains tested, with a paradoxical effect observed at high concentrations in two clinical isolates. Further, cranberry PACs were additive in combination with traditional antifungals. Cranberry PACs reduced C. albicans adherence to both polystyrene and silicone. Supplementation of the medium with iron reduced the efficacy of cranberry PACs against biofilms. These findings indicate that cranberry PACs have excellent in vitro activity against C. albicans biofilm formation in artificial urine. We present preliminary evidence that cranberry PAC activity against C. albicans biofilm formation is due to anti-adherence properties and/or iron chelation.

  6. Effects of low-level laser irradiation on the pathogenicity of Candida albicans: in vitro and in vivo study.

    Science.gov (United States)

    Seyedmousavi, Seyedmojtaba; Hashemi, Seyed Jamal; Rezaie, Sasan; Fateh, Mohsen; Djavid, Gholamreza Esmaeeli; Zibafar, Ensieh; Morsali, Farhad; Zand, Nasrin; Alinaghizadeh, Mohammadreza; Ataie-Fashtami, Leila

    2014-06-01

    The purpose of this study was to evaluate the effects of low-level laser irradiation (LLLI) on the in vitro growth characteristics and in vivo pathogenicity of Candida albicans in a murine model in the absence of a photosensitizer. C. albicans is an opportunistic commensal organism that causes a wide variety of diseases in human beings, ranging from superficial infections to life-threatening invasive candidiasis. The incidence of C. albicans infection is increasing, because of the greater frequency of acquired immunodeficiency conditions. A high recurrence rate has been reported for vulvovaginal and oral candidiasis, despite the best available treatments. Therefore, the search for new treatment modalities seems quite rational. Candida culture plates were exposed to common clinical energies of LLLI: 3, 5, 10, and 20 J at 685 nm (BTL Laser 5000, Medicinos Projektai, Czech Republic, Prague, max power output 50 mW) and 3, 5, 10, 30, and 50 J at 830 nm (BTL Laser 5000, Medicinos Projektai, Czech Republic, Prague, max power output 400 mW). Following LLLI with energies >10 J at both 685 and 830 nm wavelengths, statistically significant effects were observed in vitro on the turbidimetric growth kinetics of C. albicans and in vivo on the survival rate of infected mice (p value ≤ 0.05). Therefore, this energy could be considered a threshold for clinical investigation. Translating our data into the clinical setting, it can be proposed that a direct laser-based approach without using a photosensitizing dye can significantly reduce the pathogenicity of Candida albicans. It can also be concluded that laser light at specific wavelengths could be a possible promising novel treatment for superficial and mucocutaneous C. albicans infections.

  7. Lactobacillus reuteri strain combination in Helicobacter pylori infection: a randomized, double-blind, placebo-controlled study.

    Science.gov (United States)

    Francavilla, Ruggiero; Polimeno, Lorenzo; Demichina, Antonella; Maurogiovanni, Giovanni; Principi, Beatrice; Scaccianoce, Giuseppe; Ierardi, Enzo; Russo, Francesco; Riezzo, Giuseppe; Di Leo, Alfredo; Cavallo, Luciano; Francavilla, Antonio; Versalovic, James

    2014-01-01

    The goals of this study were to investigate the role of a new probiotic preparation (Lactobacillus reuteri DSM 17938 and L. reuteri ATCC PTA 6475) in Helicobacter pylori infection. Specific probiotic strains play a role in H. pylori infection for their ability to decrease bacterial load and gastritis, prevent antibiotic-associated side effects, and increase the eradication rate. This is a prospective, double-blind, randomized, placebo-controlled study in a tertiary care setting. A total of 100 H. pylori-positive naive patients received either L. reuteri combination (2×10 Colony Forming Units) or placebo during a 3-phase study (pre-eradication, eradication, and follow-up). All underwent C urea breath test (C-UBT), blood assessments of gastrin-17 (G17), endoscopy, and the Gastrointestinal Symptom Rating Scale. Eradication was confirmed by C-UBT 8 weeks after the completion of therapy. Fifty patients were allocated in each group. During pre-eradication period, C-UBT δ decreased by 13% in L. reuteri combination as compared with a 4% increase in placebo (-13.2±34% vs. 4.3±27%; Preuteri combination (6.8±2.9 vs. 4±3.1; Preuteri combination as compared with placebo-reported side effects (40.9% vs. 62.8%; Preuteri combination (28% vs. 12%; Preuteri combination and 65.9% in placebo (P=NS). L. reuteri combination increased eradication rate by 9.1% (odds ratio: 1.5). L. reuteri combination alone is able to exert an inhibitory effect on H. pylori growth, and when administered with eradication therapy, it determines a significant reduction in antibiotic-associated side effects. Moreover, L. reuteri combination was able to decrease serum G17 levels and to (not significantly) increase the H. pylori-eradication rate.

  8. The role of Candida albicans homologous recombination factors Rad54 and Rdh54 in DNA damage sensitivity

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    White Theodore C

    2011-09-01

    Full Text Available Abstract Background The fungal pathogen Candida albicans is frequently seen in immune suppressed patients, and resistance to one of the most widely used antifungals, fluconazole (FLC, can evolve rapidly. In recent years it has become clear that plasticity of the Candida albicans genome contributes to drug resistance through loss of heterozygosity (LOH at resistance genes and gross chromosomal rearrangements that amplify gene copy number of resistance associated genes. This study addresses the role of the homologous recombination factors Rad54 and Rdh54 in cell growth, DNA damage and FLC resistance in Candida albicans. Results The data presented here support a role for homologous recombination in cell growth and DNA damage sensitivity, as Candida albicans rad54Δ/rad54Δ mutants were hypersensitive to MMS and menadione, and had an aberrant cell and nuclear morphology. The Candida albicans rad54Δ/rad54Δ mutant was defective in invasion of Spider agar, presumably due to the altered cellular morphology. In contrast, mutation of the related gene RDH54 did not contribute significantly to DNA damage resistance and cell growth, and deletion of either Candida albicans RAD54 or Candida albicans RDH54 did not alter FLC susceptibility. Conclusions Together, these results support a role for homologous recombination in genome stability under nondamaging conditions. The nuclear morphology defects in the rad54Δ/rad54Δ mutants show that Rad54 performs an essential role during mitotic growth and that in its absence, cells arrest in G2. The viability of the single mutant rad54Δ/rad54Δ and the inability to construct the double mutant rad54Δ/rad54Δ rdh54Δ/rdh54Δ suggests that Rdh54 can partially compensate for Rad54 during mitotic growth.

  9. Editing of HIV-1 RNA by the double-stranded RNA deaminase ADAR1 stimulates viral infection

    Science.gov (United States)

    Doria, Margherita; Neri, Francesca; Gallo, Angela; Farace, Maria Giulia; Michienzi, Alessandro

    2009-01-01

    Adenosine deaminases that act on dsRNA (ADARs) are enzymes that target double-stranded regions of RNA converting adenosines into inosines (A-to-I editing) thus contributing to genome complexity and fine regulation of gene expression. It has been described that a member of the ADAR family, ADAR1, can target viruses and affect their replication process. Here we report evidence showing that ADAR1 stimulates human immuno deficiency virus type 1 (HIV-1) replication by using both editing-dependent and editing-independent mechanisms. We show that over-expression of ADAR1 in HIV-1 producer cells increases viral protein accumulation in an editing-independent manner. Moreover, HIV-1 virions generated in the presence of over-expressed ADAR1 but not an editing-inactive ADAR1 mutant are released more efficiently and display enhanced infectivity, as demonstrated by challenge assays performed with T cell lines and primary CD4+ T lymphocytes. Finally, we report that ADAR1 associates with HIV-1 RNAs and edits adenosines in the 5′ untranslated region (UTR) and the Rev and Tat coding sequence. Overall these results suggest that HIV-1 has evolved mechanisms to take advantage of specific RNA editing activity of the host cell and disclose a stimulatory function of ADAR1 in the spread of HIV-1. PMID:19651874

  10. Intrathecal spinal abscesses due to Candida albicans in an immunocompetent man.

    Science.gov (United States)

    Crane, John K

    2018-03-27

    Infections of the central nervous system due to Candida albicans are uncommon and are usually only observed in special circumstances, such as following neurosurgery or penetrating head trauma, in immunosuppressed patients, premature infants or in patients with ventriculoperitoneal shunts. The author reports a case of an immunocompetent man who presented with a thoracic intraspinal abscess due to C. albicans Despite surgical drainage and 6 weeks of high-dose fluconazole therapy, the abscess extended and recurred in the cervical spine, requiring a second operation to arrest the infection. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  11. Functional Genomic Screening Reveals Core Modulators of Echinocandin Stress Responses in Candida albicans

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    Tavia Caplan

    2018-05-01

    Full Text Available Summary: Candida albicans is a leading cause of death due to fungal infection. Treatment of systemic candidiasis often relies on echinocandins, which disrupt cell wall synthesis. Resistance is readily acquired via mutations in the drug target gene, FKS1. Both basal tolerance and resistance to echinocandins require cellular stress responses. We performed a systematic analysis of 3,030 C. albicans mutants to define circuitry governing cellular responses to echinocandins. We identified 16 genes for which deletion or transcriptional repression enhanced echinocandin susceptibility, including components of the Pkc1-MAPK signaling cascade. We discovered that the molecular chaperone Hsp90 is required for the stability of Pkc1 and Bck1, establishing key mechanisms through which Hsp90 mediates echinocandin resistance. We also discovered that perturbation of the CCT chaperonin complex causes enhanced echinocandin sensitivity, altered cell wall architecture, and aberrant septin localization. Thus, we provide insights into the mechanisms by which cellular chaperones enable crucial responses to echinocandin-induced stress. : Caplan et al. screen 3,030 Candida albicans mutants to define circuitry governing cellular responses to echinocandins, the first-line therapy for systemic candidiasis. They reveal that the molecular chaperone Hsp90 is required for stability of Pkc1 and Bck1 and that the CCT chaperonin complex is a key modulator of echinocandin susceptibility. Keywords: fungal pathogen, Candida albicans, echinocandins, Hsp90, Pkc1, CCT complex, client protein, stress response, functional genomic screen, drug resistance

  12. Candida albicans pancreatitis in a child with cystic fibrosis post lung transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Hammer, Mark M.; Sheybani, Elizabeth F. [Washington University School of Medicine, Mallinckrodt Institute of Radiology, 510 S. Kingshighway Blvd., Campus Box 8131, St. Louis, MO (United States); Zhang, Lingxin [Washington University School of Medicine, Department of Pathology, St. Louis, MO (United States); Stoll, Janis M. [Washington University School of Medicine, Division of Gastroenterology, Hepatology and Nutrition, St. Louis, MO (United States)

    2016-04-15

    We present a case of Candida albicans infection of a previously intact pancreas in a child with cystic fibrosis status post lung transplantation. Although Candida superinfection in necrotizing pancreatitis is not uncommon, this is a unique case of Candida infection of non-necrotic pancreatic parenchyma. This case presented a diagnostic dilemma for radiologists because it appeared virtually identical to acute interstitial edematous pancreatitis on imaging. Ultimately, endoscopic US-based biopsy was pursued for diagnosis. Although difficult to treat and compounded by the immunocompromised status of the child, the pancreatic infection improved with antifungal therapy. (orig.)

  13. Candida albicans pancreatitis in a child with cystic fibrosis post lung transplantation

    International Nuclear Information System (INIS)

    Hammer, Mark M.; Sheybani, Elizabeth F.; Zhang, Lingxin; Stoll, Janis M.

    2016-01-01

    We present a case of Candida albicans infection of a previously intact pancreas in a child with cystic fibrosis status post lung transplantation. Although Candida superinfection in necrotizing pancreatitis is not uncommon, this is a unique case of Candida infection of non-necrotic pancreatic parenchyma. This case presented a diagnostic dilemma for radiologists because it appeared virtually identical to acute interstitial edematous pancreatitis on imaging. Ultimately, endoscopic US-based biopsy was pursued for diagnosis. Although difficult to treat and compounded by the immunocompromised status of the child, the pancreatic infection improved with antifungal therapy. (orig.)

  14. Secreted aspartic proteases are not required for invasion of reconstituted human epithelia by Candida albicans.

    Science.gov (United States)

    Lermann, Ulrich; Morschhäuser, Joachim

    2008-11-01

    A well-known virulence attribute of the human-pathogenic yeast Candida albicans is the secretion of aspartic proteases (Saps), which may contribute to colonization and infection of different host niches by degrading tissue barriers, destroying host defence molecules, or digesting proteins for nutrient supply. The role of individual Sap isoenzymes, which are encoded by a large gene family, for the pathogenicity of C. albicans has been investigated by assessing the virulence of mutants lacking specific SAP genes and by studying the expression pattern of the SAP genes in various models of superficial and systemic infections. We used a recombination-based genetic reporter system to detect the induction of the SAP1-SAP6 genes during infection of reconstituted human vaginal epithelium. Only SAP5, but none of the other tested SAP genes, was detectably activated in this in vitro infection model. To directly address the importance of the SAP1-SAP6 genes for invasion of reconstituted human epithelia (RHE), we constructed a set of mutants of the wild-type C. albicans model strain SC5314 in which either single or multiple SAP genes were specifically deleted. Even mutants lacking all of the SAP1-SAP3 or the SAP4-SAP6 genes displayed the same capacity to invade and damage both oral and vaginal RHE as their wild-type parental strain, in contrast to a nonfilamentous efg1Delta mutant that was avirulent under these conditions. We therefore conclude from these results that the secreted aspartic proteases Sap1p-Sap6p are not required for invasion of RHE by C. albicans.

  15. Novel Aggregation Properties of Candida albicans Secreted Aspartyl Proteinase Sap6 Mediate Virulence in Oral Candidiasis.

    Science.gov (United States)

    Kumar, Rohitashw; Saraswat, Darpan; Tati, Swetha; Edgerton, Mira

    2015-07-01

    Candida albicans, a commensal fungus of the oral microbiome, causes oral candidiasis in humans with localized or systemic immune deficiencies. Secreted aspartic proteinases (Saps) are a family of 10 related proteases and are virulence factors due to their proteolytic activity, as well as their roles in adherence and colonization of host tissues. We found that mice infected sublingually with C. albicans cells overexpressing Sap6 (SAP6 OE and a Δsap8 strain) had thicker fungal plaques and more severe oral infection, while infection with the Δsap6 strain was attenuated. These hypervirulent strains had highly aggregative colony structure in vitro and higher secreted proteinase activity; however, the levels of proteinase activity of C. albicans Saps did not uniformly match their abilities to damage cultured oral epithelial cells (SCC-15 cells). Hyphal induction in cells overexpressing Sap6 (SAP6 OE and Δsap8 cells) resulted in formation of large cell-cell aggregates. These aggregates could be produced in germinated wild-type cells by addition of native or heat-inactivated Sap6. Sap6 bound only to germinated cells and increased C. albicans adhesion to oral epithelial cells. The adhesion properties of Sap6 were lost upon deletion of its integrin-binding motif (RGD) and could be inhibited by addition of RGD peptide or anti-integrin antibodies. Thus, Sap6 (but not Sap5) has an alternative novel function in cell-cell aggregation, independent of its proteinase activity, to promote infection and virulence in oral candidiasis.

  16. Effect of the Ethyl Acetate Fraction of Eugenia uniflora on Proteins Global Expression during Morphogenesis in Candida albicans.

    Science.gov (United States)

    Silva-Rocha, Walicyranison P; de Azevedo, Matheus F; Ferreira, Magda R A; da Silva, Julhiany de Fátima; Svidzinski, Terezinha I E; Milan, Eveline P; Soares, Luiz A L; Rocha, Keyla B F; Uchôa, Adriana F; Mendes-Giannini, Maria J S; Fusco Almeida, Ana M; Chaves, Guilherme M

    2017-01-01

    Candida albicans is able to switch from yeast to hyphal growth and this is an essential step for tissue invasion and establishment of infection. Due to the limited drug arsenal used to treat fungal infections and the constant emergence of resistant strains, it is important to search for new therapeutic candidates. Therefore, this study aimed to investigate by proteomic analysis the role of a natural product ( Eugenia uniflora ) in impairing hypha formation in C. albicans . We also tested the potential action of E. uniflora to prevent and treat oral candidiasis induced in a murine model of oral infection and the ability of polymorphonuclear neutrophils to phagocytize C. albicans cells treated with the ethyl acetate fraction of the extract. We found that this fraction greatly reduced hypha formation after morphogenesis induction in the presence of serum. Besides, several proteins were differentially expressed in cells treated with the fraction. Surprisingly, the ethyl acetate fraction significantly reduced phagocytosis in C. albicans (Mean 120.36 ± 36.71 yeasts/100 PMNs vs. 44.68 ± 19.84 yeasts/100 PMNs). Oral candidiasis was attenuated when C. albicans cells were either pre-incubated in the presence of E. uniflora or when the fraction was applied to the surface of the oral cavity after infection. These results were consistent with the reduction in CFU counts (2.36 vs. 1.85 Log10 CFU/ml) and attenuation of tissue damage observed with histopathological analysis of animals belonging to treated group. We also observed shorter true hyphae by direct examination and histopathological analysis, when cells were treated with the referred natural product. The E. uniflora ethyl acetate fraction was non-toxic to human cells. E. uniflora may act on essential proteins mainly related to cellular structure, reducing the capacity of filamentation and attenuating infection in a murine model, without causing any toxic effect on human cells, suggesting that it may be a future

  17. AFM force spectroscopy reveals how subtle structural differences affect the interaction strength between Candida albicans and DC-SIGN

    NARCIS (Netherlands)

    Riet, J. te; Reinieren-Beeren, I.M.J.; Figdor, C.G.; Cambi, A.

    2015-01-01

    The fungus Candida albicans is the most common cause of mycotic infections in immunocompromised hosts. Little is known about the initial interactions between Candida and immune cell receptors, such as the C-type lectin dendritic cell-specific intracellular cell adhesion molecule-3 (ICAM-3)-grabbing

  18. The Antifungal Inhibitory Concentration Effectiveness Test From Ethanol Seed Arabica Coffee (Coffea arabica) Extract Against The Growth Of Candida albicans Patient Isolate With In Vitro Method

    Science.gov (United States)

    Satria Rakatama, Adam; Pramono, Andri; Yulianti, Retno

    2018-03-01

    Candida albicans are the most frequent cause of Vulvovaginalis Candidiasis infection. Its treatment using antifungal drugs, are oftenly caused side effects. The reduction of C.albicans growth and the reduction of antifungal drugs side effect, were our main purposed. Our study objective is determine the effectiveness of inhibitory power of arabica coffee seed ethanol extract on the growth of C.albicans patient isolates. The type of this research is experimental research. Kirby-bauer method with the Saboraud Dextrose Agar (SDA) media was used in this experiment. Inhibitory zone was observed around the disc, to determine the inhibitory power. The results showed that the inhibitory zone was formed on arabica coffee seed ethanol extract on 10%, 20%, 40%, and 80% concentration. Kruskal-Wallis test results (pthe concentration groups tested against the treatment group. The inhibitory zone was formed because of biochemical compound in arabica coffee seed such as caffeine, phenol, alkaloids, flavonoids, and saponins. Inhibitory zone in C.albicans patient isolates were smaller compared with C.albicans ATCC 90028 as gold standard. This showed that the virulence of C.albicans from patients isolates were higher. We concluded that arabica coffee seed ethanol extract could inhibiting the growth of C.albicans patient isolates. Optimization of coffee seed ethanol extract to obtain maximum active ingredients still needs to be done. This knowledge is expected to be used for the beginning manufacturer antifungal drug from natural product.

  19. A phenotypic profile of the Candida albicans regulatory network.

    Directory of Open Access Journals (Sweden)

    Oliver R Homann

    2009-12-01

    Full Text Available Candida albicans is a normal resident of the gastrointestinal tract and also the most prevalent fungal pathogen of humans. It last shared a common ancestor with the model yeast Saccharomyces cerevisiae over 300 million years ago. We describe a collection of 143 genetically matched strains of C. albicans, each of which has been deleted for a specific transcriptional regulator. This collection represents a large fraction of the non-essential transcription circuitry. A phenotypic profile for each mutant was developed using a screen of 55 growth conditions. The results identify the biological roles of many individual transcriptional regulators; for many, this work represents the first description of their functions. For example, a quarter of the strains showed altered colony formation, a phenotype reflecting transitions among yeast, pseudohyphal, and hyphal cell forms. These transitions, which have been closely linked to pathogenesis, have been extensively studied, yet our work nearly doubles the number of transcriptional regulators known to influence them. As a second example, nearly a quarter of the knockout strains affected sensitivity to commonly used antifungal drugs; although a few transcriptional regulators have previously been implicated in susceptibility to these drugs, our work indicates many additional mechanisms of sensitivity and resistance. Finally, our results inform how transcriptional networks evolve. Comparison with the existing S. cerevisiae data (supplemented by additional S. cerevisiae experiments reported here allows the first systematic analysis of phenotypic conservation by orthologous transcriptional regulators over a large evolutionary distance. We find that, despite the many specific wiring changes documented between these species, the general phenotypes of orthologous transcriptional regulator knockouts are largely conserved. These observations support the idea that many wiring changes affect the detailed architecture of

  20. A phenotypic profile of the Candida albicans regulatory network.

    Science.gov (United States)

    Homann, Oliver R; Dea, Jeanselle; Noble, Suzanne M; Johnson, Alexander D

    2009-12-01

    Candida albicans is a normal resident of the gastrointestinal tract and also the most prevalent fungal pathogen of humans. It last shared a common ancestor with the model yeast Saccharomyces cerevisiae over 300 million years ago. We describe a collection of 143 genetically matched strains of C. albicans, each of which has been deleted for a specific transcriptional regulator. This collection represents a large fraction of the non-essential transcription circuitry. A phenotypic profile for each mutant was developed using a screen of 55 growth conditions. The results identify the biological roles of many individual transcriptional regulators; for many, this work represents the first description of their functions. For example, a quarter of the strains showed altered colony formation, a phenotype reflecting transitions among yeast, pseudohyphal, and hyphal cell forms. These transitions, which have been closely linked to pathogenesis, have been extensively studied, yet our work nearly doubles the number of transcriptional regulators known to influence them. As a second example, nearly a quarter of the knockout strains affected sensitivity to commonly used antifungal drugs; although a few transcriptional regulators have previously been implicated in susceptibility to these drugs, our work indicates many additional mechanisms of sensitivity and resistance. Finally, our results inform how transcriptional networks evolve. Comparison with the existing S. cerevisiae data (supplemented by additional S. cerevisiae experiments reported here) allows the first systematic analysis of phenotypic conservation by orthologous transcriptional regulators over a large evolutionary distance. We find that, despite the many specific wiring changes documented between these species, the general phenotypes of orthologous transcriptional regulator knockouts are largely conserved. These observations support the idea that many wiring changes affect the detailed architecture of the circuit, but

  1. Proteus vulgaris and Proteus mirabilis Decrease Candida albicans Biofilm Formation by Suppressing Morphological Transition to Its Hyphal Form.

    Science.gov (United States)

    Lee, Kyoung Ho; Park, Su Jung; Choi, Sun Ju; Park, Joo Young

    2017-11-01

    Candida albicans (C. albicans) and Proteus species are causative agents in a variety of opportunistic nosocomial infections, and their ability to form biofilms is known to be a virulence factor. In this study, the influence of co-cultivation with Proteus vulgaris (P. vulgaris) and Proteus mirabilis (P. mirabilis) on C. albicans biofilm formation and its underlying mechanisms were examined. XTT reduction assays were adopted to measure biofilm formation, and viable colony counts were performed to quantify yeast growth. Real-time reverse transcriptase polymerase chain reaction was used to evaluate the expression of yeast-specific genes (rhd1 and rbe1), filament formation inhibiting genes (tup1 and nrg1), and hyphae-related genes (als3, ece1, hwp1, and sap5). Candida biofilm formation was markedly inhibited by treatment with either living or heat-killed P. vulgaris and P. mirabilis. Proteus-cultured supernatant also inhibited Candida biofilm formation. Likewise, treatment with live P. vulgaris or P. mirabilis or with Proteus-cultured supernatant decreased expression of hyphae-related C. albicans genes, while the expression of yeast-specific genes and the filament formation inhibiting genes of C. albicans were increased. Heat-killed P. vulgaris and P. mirabilis treatment, however, did not affect the expression of C. albicans morphology-related genes. These results suggest that secretory products from P. vulgaris and P. mirabilis regulate the expression of genes related to morphologic changes in C. albicans such that transition from the yeast form to the hyphal form can be inhibited. © Copyright: Yonsei University College of Medicine 2017

  2. Toxicity of nalidixic acid on candida albicans, Saccharomyces cerevisiae, and Kluyveromyces lactis.

    Science.gov (United States)

    Sobieski, R J; Brewer, A R

    1976-03-01

    The antibacterial drug nalidixic acid (Nal) can suppress the growth of Candida albicans at levels of the drug normally found in urine. Growth suppression increases as drug levels are increased, and Nal also causes a similar proportional inhibition of the synthesis of all cellular macromolecules. However, growth temperature (25 versus 37 C) and the divalent cations Mg(2+) and Mn(2+) can increase C. albicans resistance to Nal. Also, nitrogen depletion of Candida shows that Nal-treated and untreated cells exhibit no difference in leucine uptake during readaptation to nitrogen. In Nal-treated, nitrogen-starved cells, ribonucleic acid and deoxyribonucleic acid (DNA) biosynthesis are less affected than in unstarved Nal-treated cells, but of the two nucleic acids DNA synthesis is the most affected. Nal-resistant strains of C. albicans exhibit a slight toxicity for macromolecular synthesis. Nal treatment of a synchronized population of Saccharomyces cerevisiae results in an increase in the culture mean doubling time of, at most, 20%, but Nal causes the loss of synchronous cell division. With a synchronized population of Kluyveromyces lactis, Nal causes an increase in the mean doubling time of upwards of 300%, with synchrony of cell division being maintained. It is known that S. cerevisiae asynchronously synthesizes mitochondrial DNA during the cell cycle, whereas with K. lactis it is synchronous. Thus, with C. albicans Nal toxicity is dependent both on the dose and the physiological state of the cell. Furthermore, Nal inhibits growth of yeast with synchronous mitochondrial DNA synthesis more adversely than yeast with asynchronous mitochondrial DNA synthesis.

  3. Therapeutic potential of thiazolidinedione-8 as an antibiofilm agent against Candida albicans.

    Directory of Open Access Journals (Sweden)

    Mark Feldman

    Full Text Available Candida albicans is known as a commensal microorganism but it is also the most common fungal pathogen in humans, causing both mucosal and systemic infections. Biofilm-associated C. albicans infections present clinically important features due to their high levels of resistance to traditional antifungal agents. Quorum sensing is closely associated with biofilm formation and increasing fungal pathogenicity. We investigated the ability of the novel bacterial quorum sensing quencher thiazolidinedione-8 (S-8 to inhibit the formation of, and eradication of mature C. albicans biofilms. In addition, the capability of S-8 to alter fungal adhesion to mammalian cells was checked. S-8 exhibited specific antibiofilm and antiadhesion activities against C. albicans, at four- to eightfold lower concentrations than the minimum inhibitory concentration (MIC. Using fluorescence microscopy, we observed that S-8 dose-dependently reduces C. albicans-GFP binding to RAW macrophages. S-8 at sub-MICs also interfered with fungal morphogenesis by inhibiting the yeast-to-hyphal form transition. In addition, the tested agent strongly affected fungal cell wall characteristics by modulating its hydrophobicity. We evaluated the molecular mode of S-8 antibiofilm and antiadhesion activities using real-time RT-PCR. The expression levels of genes associated with biofilm formation, adhesion and filamentation, HWP1, ALS3 and EAP1, respectively, were dose-dependently downregulated by S-8. Transcript levels of UME6, responsible for long-term hyphal maintenance, were also significantly decreased by the tested agent. Both signaling pathways of hyphal formation-cAMP-PKA and MAPK-were interrupted by S-8. Their upstream general regulator RAS1 was markedly suppressed by S-8. In addition, the expression levels of MAPK cascade components CST20, HST7 and CPH1 were downregulated by S-8. Finally, transcriptional repressors of filament formation, TUP1 and NRG1, were dramatically upregulated by our

  4. Disruption of the Candida albicans TPS1 Gene Encoding Trehalose-6-Phosphate Synthase Impairs Formation of Hyphae and Decreases Infectivity†

    Science.gov (United States)

    Zaragoza, Oscar; Blazquez, Miguel A.; Gancedo, Carlos

    1998-01-01

    The TPS1 gene from Candida albicans, which encodes trehalose-6-phosphate synthase, has been cloned by functional complementation of a tps1 mutant from Saccharomyces cerevisiae. In contrast with the wild-type strain, the double tps1/tps1 disruptant did not accumulate trehalose at stationary phase or after heat shock. Growth of the tps1/tps1 disruptant at 30°C was indistinguishable from that of the wild type. However, at 42°C it did not grow on glucose or fructose but grew normally on galactose or glycerol. At 37°C, the yeast-hypha transition in the mutant in glucose-calf serum medium did not occur. During growth at 42°C, the mutant did not form hyphae in galactose or in glycerol. Some of the growth defects observed may be traced to an unbalanced sugar metabolism that reduces the cellular content of ATP. Mice inoculated with 106 CFU of the tps1/tps1 mutant did not show visible symptoms of infection 16 days after inoculation, while those similarly inoculated with wild-type cells were dead 12 days after inoculation. PMID:9683476

  5. Isolation of a variant of Candida albicans.

    Science.gov (United States)

    Buckley, H R; Price, M R; Daneo-Moore, L

    1982-01-01

    During the course of Candida albicans antigen production, a variant of this organism was encountered which did not produce hyphae at 37 degrees C. Presented here are some of the characteristics of this variant. It produces hyphae at 25 degrees C on cornmeal agar and synthetic medium plus N-acetylglucosamine and Tween 80. At 37 degrees C, it does not produce hyphae on these media, although C. albicans normally does produce hyphae under these circumstances. In liquid synthetic medium, this variant does not produce hyphae at 37 degrees C. The variant strain was analyzed for DNA, RNA, protein content, and particle size. After 50 to 70 h in balanced exponential-phase growth, particle size distribution was narrow, and there were no differences in the DNA, RNA, or protein content per particle in the two strains. When balanced exponential-phase cultures were brought into stationary phase, both strains contained the same amount of DNA per cell. Images PMID:6752021

  6. Isolation of a variant of Candida albicans.

    Science.gov (United States)

    Buckley, H R; Price, M R; Daneo-Moore, L

    1982-09-01

    During the course of Candida albicans antigen production, a variant of this organism was encountered which did not produce hyphae at 37 degrees C. Presented here are some of the characteristics of this variant. It produces hyphae at 25 degrees C on cornmeal agar and synthetic medium plus N-acetylglucosamine and Tween 80. At 37 degrees C, it does not produce hyphae on these media, although C. albicans normally does produce hyphae under these circumstances. In liquid synthetic medium, this variant does not produce hyphae at 37 degrees C. The variant strain was analyzed for DNA, RNA, protein content, and particle size. After 50 to 70 h in balanced exponential-phase growth, particle size distribution was narrow, and there were no differences in the DNA, RNA, or protein content per particle in the two strains. When balanced exponential-phase cultures were brought into stationary phase, both strains contained the same amount of DNA per cell.

  7. Lack of clinical AIDS in SIV-infected sooty mangabeys with significant CD4+ T cell loss is associated with double-negative T cells

    Science.gov (United States)

    Milush, Jeffrey M.; Mir, Kiran D.; Sundaravaradan, Vasudha; Gordon, Shari N.; Engram, Jessica; Cano, Christopher A.; Reeves, Jacqueline D.; Anton, Elizabeth; O’Neill, Eduardo; Butler, Eboneé; Hancock, Kathy; Cole, Kelly S.; Brenchley, Jason M.; Else, James G.; Silvestri, Guido; Sodora, Donald L.

    2011-01-01

    SIV infection of natural host species such as sooty mangabeys results in high viral replication without clinical signs of simian AIDS. Studying such infections is useful for identifying immunologic parameters that lead to AIDS in HIV-infected patients. Here we have demonstrated that acute, SIV-induced CD4+ T cell depletion in sooty mangabeys does not result in immune dysfunction and progression to simian AIDS and that a population of CD3+CD4–CD8– T cells (double-negative T cells) partially compensates for CD4+ T cell function in these animals. Passaging plasma from an SIV-infected sooty mangabey with very few CD4+ T cells to SIV-negative animals resulted in rapid loss of CD4+ T cells. Nonetheless, all sooty mangabeys generated SIV-specific antibody and T cell responses and maintained normal levels of plasma lipopolysaccharide. Moreover, all CD4-low sooty mangabeys elicited a de novo immune response following influenza vaccination. Such preserved immune responses as well as the low levels of immune activation observed in these animals were associated with the presence of double-negative T cells capable of producing Th1, Th2, and Th17 cytokines. These studies indicate that SIV-infected sooty mangabeys do not appear to rely entirely on CD4+ T cells to maintain immunity and identify double-negative T cells as a potential subset of cells capable of performing CD4+ T cell–like helper functions upon SIV-induced CD4+ T cell depletion in this species. PMID:21317533

  8. The Absence of N-Acetyl-D-glucosamine Causes Attenuation of Virulence of Candida albicans upon Interaction with Vaginal Epithelial Cells In Vitro

    Directory of Open Access Journals (Sweden)

    Máté Manczinger

    2015-01-01

    Full Text Available To better understand the molecular events underlying vulvovaginal candidiasis, we established an in vitro system. Immortalized vaginal epithelial cells were infected with live, yeast form C. albicans and C. albicans cultured in the same medium without vaginal epithelial cells were used as control. In both cases a yeast to hyphae transition was robustly induced. Whole transcriptome sequencing was used to identify specific gene expression changes in C. albicans. Numerous genes leading to a yeast to hyphae transition and hyphae specific genes were upregulated in the control hyphae and the hyphae in response to vaginal epithelial cells. Strikingly, the GlcNAc pathway was exclusively triggered by vaginal epithelial cells. Functional analysis in our in vitro system revealed that the GlcNAc biosynthesis is involved in the adherence to, and the ability to kill, vaginal epithelial cells in vitro, thus indicating the key role for this pathway in the virulence of C. albicans upon vulvovaginal candidiasis.

  9. The Absence of N-Acetyl-D-glucosamine Causes Attenuation of Virulence of Candida albicans upon Interaction with Vaginal Epithelial Cells In Vitro

    Science.gov (United States)

    Manczinger, Máté; Bocsik, Alexandra; Kocsis, Gabriella F.; Vörös, Andrea; Hegedűs, Zoltán; Marton, Annamária; Vízler, Csaba; Tubak, Vilmos; Deli, Mária; Kemény, Lajos; Nagy, István; Lakatos, Lóránt

    2015-01-01

    To better understand the molecular events underlying vulvovaginal candidiasis, we established an in vitro system. Immortalized vaginal epithelial cells were infected with live, yeast form C. albicans and C. albicans cultured in the same medium without vaginal epithelial cells were used as control. In both cases a yeast to hyphae transition was robustly induced. Whole transcriptome sequencing was used to identify specific gene expression changes in C. albicans. Numerous genes leading to a yeast to hyphae transition and hyphae specific genes were upregulated in the control hyphae and the hyphae in response to vaginal epithelial cells. Strikingly, the GlcNAc pathway was exclusively triggered by vaginal epithelial cells. Functional analysis in our in vitro system revealed that the GlcNAc biosynthesis is involved in the adherence to, and the ability to kill, vaginal epithelial cells in vitro, thus indicating the key role for this pathway in the virulence of C. albicans upon vulvovaginal candidiasis. PMID:26366412

  10. Triclosan antagonizes fluconazole activity against Candida albicans.

    LENUS (Irish Health Repository)

    Higgins, J

    2012-01-01

    Triclosan is a broad-spectrum antimicrobial compound commonly used in oral hygiene products. Investigation of its activity against Candida albicans showed that triclosan was fungicidal at concentrations of 16 mg\\/L. However, at subinhibitory concentrations (0.5-2 mg\\/L), triclosan antagonized the activity of fluconazole. Although triclosan induced CDR1 expression in C. albicans, antagonism was still observed in cdr1Δ and cdr2Δ strains. Triclosan did not affect fluconazole uptake or alter total membrane sterol content, but did induce the expression of FAS1 and FAS2, indicating that its mode of action may involve inhibition of fatty acid synthesis, as it does in prokaryotes. However, FAS2 mutants did not exhibit increased susceptibility to triclosan, and overexpression of both FAS1 and FAS2 alleles did not alter triclosan susceptibility. Unexpectedly, the antagonistic effect was specific for C. albicans under hypha-inducing conditions and was absent in the non-filamentous efg1Δ strain. This antagonism may be due to the membranotropic activity of triclosan and the unique composition of hyphal membranes.

  11. Posaconazole exhibits in vitro and in vivo synergistic antifungal activity with caspofungin or FK506 against Candida albicans.

    Directory of Open Access Journals (Sweden)

    Ying-Lien Chen

    Full Text Available The object of this study was to test whether posaconazole, a broad-spectrum antifungal agent inhibiting ergosterol biosynthesis, exhibits synergy with the β-1,3 glucan synthase inhibitor caspofungin or the calcineurin inhibitor FK506 against the human fungal pathogen Candida albicans. Although current drug treatments for Candida infection are often efficacious, the available antifungal armamentarium may not be keeping pace with the increasing incidence of drug resistant strains. The development of drug combinations or novel antifungal drugs to address emerging drug resistance is therefore of general importance. Combination drug therapies are employed to treat patients with HIV, cancer, or tuberculosis, and has considerable promise in the treatment of fungal infections like cryptococcal meningitis and C. albicans infections. Our studies reported here demonstrate that posaconazole exhibits in vitro synergy with caspofungin or FK506 against drug susceptible or resistant C. albicans strains. Furthermore, these combinations also show in vivo synergy against C. albicans strain SC5314 and its derived echinocandin-resistant mutants, which harbor an S645Y mutation in the CaFks1 β-1,3 glucan synthase drug target, suggesting potential therapeutic applicability for these combinations in the future.

  12. IL-1 Coordinates the Neutrophil Response to C. albicans in the Oral Mucosa.

    Directory of Open Access Journals (Sweden)

    Simon Altmeier

    2016-09-01

    Full Text Available Mucosal infections with Candida albicans belong to the most frequent forms of fungal diseases. Host protection is conferred by cellular immunity; however, the induction of antifungal immunity is not well understood. Using a mouse model of oropharyngeal candidiasis (OPC we show that interleukin-1 receptor (IL-1R signaling is critical for fungal control at the onset of infection through its impact on neutrophils at two levels. We demonstrate that both the recruitment of circulating neutrophils to the site of infection and the mobilization of newly generated neutrophils from the bone marrow depended on IL-1R. Consistently, IL-1R-deficient mice displayed impaired chemokine production at the site of infection and defective secretion of granulocyte colony-stimulating factor (G-CSF in the circulation in response to C. albicans. Strikingly, endothelial cells were identified as the primary cellular source of G-CSF during OPC, which responded to IL-1α that was released from keratinocytes in the infected tissue. The IL-1-dependent crosstalk between two different cellular subsets of the nonhematopoietic compartment was confirmed in vitro using a novel murine tongue-derived keratinocyte cell line and an established endothelial cell line. These data establish a new link between IL-1 and granulopoiesis in the context of fungal infection. Together, we identified two complementary mechanisms coordinating the neutrophil response in the oral mucosa, which is critical for preventing fungal growth and dissemination, and thus protects the host from disease.

  13. IL-1 Coordinates the Neutrophil Response to C. albicans in the Oral Mucosa.

    Science.gov (United States)

    Altmeier, Simon; Toska, Albulena; Sparber, Florian; Teijeira, Alvaro; Halin, Cornelia; LeibundGut-Landmann, Salomé

    2016-09-01

    Mucosal infections with Candida albicans belong to the most frequent forms of fungal diseases. Host protection is conferred by cellular immunity; however, the induction of antifungal immunity is not well understood. Using a mouse model of oropharyngeal candidiasis (OPC) we show that interleukin-1 receptor (IL-1R) signaling is critical for fungal control at the onset of infection through its impact on neutrophils at two levels. We demonstrate that both the recruitment of circulating neutrophils to the site of infection and the mobilization of newly generated neutrophils from the bone marrow depended on IL-1R. Consistently, IL-1R-deficient mice displayed impaired chemokine production at the site of infection and defective secretion of granulocyte colony-stimulating factor (G-CSF) in the circulation in response to C. albicans. Strikingly, endothelial cells were identified as the primary cellular source of G-CSF during OPC, which responded to IL-1α that was released from keratinocytes in the infected tissue. The IL-1-dependent crosstalk between two different cellular subsets of the nonhematopoietic compartment was confirmed in vitro using a novel murine tongue-derived keratinocyte cell line and an established endothelial cell line. These data establish a new link between IL-1 and granulopoiesis in the context of fungal infection. Together, we identified two complementary mechanisms coordinating the neutrophil response in the oral mucosa, which is critical for preventing fungal growth and dissemination, and thus protects the host from disease.

  14. Modelling the regulation of thermal adaptation in Candida albicans, a major fungal pathogen of humans.

    Directory of Open Access Journals (Sweden)

    Michelle D Leach

    Full Text Available Eukaryotic cells have evolved mechanisms to sense and adapt to dynamic environmental changes. Adaptation to thermal insults, in particular, is essential for their survival. The major fungal pathogen of humans, Candida albicans, is obligately associated with warm-blooded animals and hence occupies thermally buffered niches. Yet during its evolution in the host it has retained a bona fide heat shock response whilst other stress responses have diverged significantly. Furthermore the heat shock response is essential for the virulence of C. albicans. With a view to understanding the relevance of this response to infection we have explored the dynamic regulation of thermal adaptation using an integrative systems biology approach. Our mathematical model of thermal regulation, which has been validated experimentally in C. albicans, describes the dynamic autoregulation of the heat shock transcription factor Hsf1 and the essential chaperone protein Hsp90. We have used this model to show that the thermal adaptation system displays perfect adaptation, that it retains a transient molecular memory, and that Hsf1 is activated during thermal transitions that mimic fever. In addition to providing explanations for the evolutionary conservation of the heat shock response in this pathogen and the relevant of this response to infection, our model provides a platform for the analysis of thermal adaptation in other eukaryotic cells.

  15. Candida albicans response to spaceflight (NASA STS-115)

    Data.gov (United States)

    National Aeronautics and Space Administration — This study presents the first global transcriptional profiling and phenotypic characterization of the major human opportunistic fungal pathogen Candida albicans...

  16. Inequalities and Duality in Gene Coexpression Networks of HIV-1 Infection Revealed by the Combination of the Double-Connectivity Approach and the Gini's Method

    Directory of Open Access Journals (Sweden)

    Chuang Ma

    2011-01-01

    Full Text Available The symbiosis (Sym and pathogenesis (Pat is a duality problem of microbial infection, including HIV/AIDS. Statistical analysis of inequalities and duality in gene coexpression networks (GCNs of HIV-1 infection may gain novel insights into AIDS. In this study, we focused on analysis of GCNs of uninfected subjects and HIV-1-infected patients at three different stages of viral infection based on data deposited in the GEO database of NCBI. The inequalities and duality in these GCNs were analyzed by the combination of the double-connectivity (DC approach and the Gini's method. DC analysis reveals that there are significant differences between positive and negative connectivity in HIV-1 stage-specific GCNs. The inequality measures of negative connectivity and edge weight are changed more significantly than those of positive connectivity and edge weight in GCNs from the HIV-1 uninfected to the AIDS stages. With the permutation test method, we identified a set of genes with significant changes in the inequality and duality measure of edge weight. Functional analysis shows that these genes are highly enriched for the immune system, which plays an essential role in the Sym-Pat duality (SPD of microbial infections. Understanding of the SPD problems of HIV-1 infection may provide novel intervention strategies for AIDS.

  17. Diferenciação de cepas de Candida albicans pelo sistema killer

    Directory of Open Access Journals (Sweden)

    Regina Celia Cândido

    1995-12-01

    Full Text Available Foi estudado o efeito killer de 9 cepas padrão de leveduras sobre 146 amostras de Candida albicans isoladas dos seguintes espécimes clínicos: mucosa bucal, fezes, lavado brônquico, escarro, secreção vaginal, urina, lesão de pele, lesão de unha e sangue. Usando este sistema foi possível diferenciar 23 biotipos de C. albicans. Os biotipos 211, 111 e 811 foram os mais freqüentemente isolados. A maioria das amostras de C. albicans (98,6% foi sensível a pelo menos uma ou mais das 9 cepas killer. Empregando- se este sistema foi possível demonstrar que 2 pacientes albergavam mesmo biotipo killer, respectivamente, 111 e 211, em diferentes espécimes clínicos, e em outro paciente, o mesmo biotipo (211 foi isolado de hemoculturas realizadas em ocasiões distintas. O uso do sistema killer para diferenciar os tipos entre as espécies de leveduras patogênicas, pode ser um método útil para estabelecer a eventual fonte de infecção, constituindo uma ajuda valiosa para o controle e vigilância de infecções nosocomiais causadas por leveduras.The authors studied the killer effect of nine standard strains of yeasts on 146 samples of Candida albicans isolated from the following clinical specimens: oral mucosa, feces, bronchial wash, sputum, vaginal secretion, urine, skin lesion, nail lesion and blood. Using this system it was possible to differentiate 23 biotypes of Candida albicans. The biotypes 211, 111 and 811 were most frequently isolated. Most of the samples of C. albicans (98.6% were sensitive to at least one or more of the nine killer strains. Using the killer system it was possible to show that two patients harbored the same killer biotypes, 111 and 211, respectively, in different clinical specimens and another patient harbored the same biotype (211 in blood cultures effected in different ocasions. The utilization of the killer system to differentiate types among species of pathogenic yeasts can be a useful method to stablish the eventual

  18. Inhibition of Candida albicans by Fluvastatin Is Dependent on pH

    Directory of Open Access Journals (Sweden)

    Martin Schmidt

    2009-01-01

    Full Text Available The cholesterol-lowering drug fluvastatin (FS has an inhibitory effect on the growth of the pathogenic yeast Candida albicans that is dependent on the pH of the medium. At the low pH value of the vagina, FS is growth inhibitory at low and at high concentrations, while at intermediate concentrations (1–10 mM, it has no inhibitory effect. Examination of the effect of the common antifungal drug fluconazole in combination with FS demonstrates drug interactions in the low concentration range. Determination of intracellular stress and the activity of the FS target enzyme HMG-CoA reductase confirm our hypothesis that in the intermediate dose range adjustments to the sterol biosynthesis pathway can compensate for the action of FS. We conclude that the pH dependent uptake of FS across yeast membranes might make FS combination therapy an attractive possibility for treatment of vaginal C. albicans infections.

  19. IL-17-mediated immunity to the opportunistic fungal pathogen Candida albicans

    Science.gov (United States)

    Conti, Heather R.; Gaffen, Sarah L.

    2015-01-01

    IL-17 (IL-17A) has emerged as a key mediator of protection against extracellular microbes, but this cytokine also drives pathology in various autoimmune diseases. Overwhelming data in both humans and mice reveal a clear and surprisingly specific role for IL-17 in protection against the fungus Candida albicans, a commensal of the human oral cavity, gastrointestinal tract and reproductive mucosa. The IL-17 pathway regulates antifungal immunity through upregulation of pro-inflammatory cytokines including IL-6, neutrophil-recruiting chemokines such as CXCL1 and CXCL5 and antimicrobial peptides such as the defensins, which act in concert to limit fungal overgrowth. This review will focus on diseases caused by C. albicans, the role of IL-17-mediated immunity in candidiasis, and the implications for clinical therapies for both autoimmune conditions and fungal infections. PMID:26188072

  20. Plasma membrane organization promotes virulence of the human fungal pathogen Candida albicans.

    Science.gov (United States)

    Douglas, Lois M; Konopka, James B

    2016-03-01

    Candida albicans is a human fungal pathogen capable of causing lethal systemic infections. The plasma membrane plays key roles in virulence because it not only functions as a protective barrier, it also mediates dynamic functions including secretion of virulence factors, cell wall synthesis, invasive hyphal morphogenesis, endocytosis, and nutrient uptake. Consistent with this functional complexity, the plasma membrane is composed of a wide array of lipids and proteins. These components are organized into distinct domains that will be the topic of this review. Some of the plasma membrane domains that will be described are known to act as scaffolds or barriers to diffusion, such as MCC/eisosomes, septins, and sites of contact with the endoplasmic reticulum. Other zones mediate dynamic processes, including secretion, endocytosis, and a special region at hyphal tips that facilitates rapid growth. The highly organized architecture of the plasma membrane facilitates the coordination of diverse functions and promotes the pathogenesis of C. albicans.

  1. Plasma membrane organization promotes virulence of the human fungal pathogen Candida albicans

    Science.gov (United States)

    Douglas, Lois M.; Konopka, James. B.

    2017-01-01

    Candida albicans is a human fungal pathogen capable of causing lethal systemic infections. The plasma membrane plays key roles in virulence because it not only functions as a protective barrier, it also mediates dynamic functions including secretion of virulence factors, cell wall synthesis, invasive hyphal morphogenesis, endocytosis, and nutrient uptake. Consistent with this functional complexity, the plasma membrane is composed of a wide array of lipids and proteins. These components are organized into distinct domains that will be the topic of this review. Some of the plasma membrane domains that will be described are known to act as scaffolds or barriers to diffusion, such as MCC/eisosomes, septins, and sites of contact with the endoplasmic reticulum. Other zones mediate dynamic processes, including secretion, endocytosis, and a special region at hyphal tips that facilitates rapid growth. The highly organized architecture of the plasma membrane facilitates the coordination of diverse functions and promotes the pathogenesis of C. albicans. PMID:26920878

  2. Randomized Trial Evaluating the Impact of Ribavirin Mono-Therapy and Double Dosing on Viral Kinetics, Ribavirin Pharmacokinetics and Anemia in Hepatitis C Virus Genotype 1 Infection

    DEFF Research Database (Denmark)

    Waldenström, Jesper; Westin, Johan; Nyström, Kristina

    2016-01-01

    In this pilot study (RibaC), 58 hepatitis C virus (HCV) genotype 1 infected treatment-naïve patients were randomized to (i) 2 weeks ribavirin double dosing concomitant with pegylated interferon-α (pegIFN-α), (ii) 4 weeks ribavirin mono-therapy prior to adding pegIFN-α, or (iii) standard-of-care (......In this pilot study (RibaC), 58 hepatitis C virus (HCV) genotype 1 infected treatment-naïve patients were randomized to (i) 2 weeks ribavirin double dosing concomitant with pegylated interferon-α (pegIFN-α), (ii) 4 weeks ribavirin mono-therapy prior to adding pegIFN-α, or (iii) standard......, by day 14, double dosing entailed a greater hemoglobin decline as compared to SOC (2.2 vs. 1.4 g/dL; P = 0.03). Conclusion: Ribavirin down-regulates IP-10, and may have an anti-viral effect differently regulated across IL28B genotypes....

  3. Defective IL-17- and IL-22-dependent mucosal host response to Candida albicans determines susceptibility to oral candidiasis in mice expressing the HIV-1 transgene.

    Science.gov (United States)

    Goupil, Mathieu; Cousineau-Côté, Vincent; Aumont, Francine; Sénéchal, Serge; Gaboury, Louis; Hanna, Zaher; Jolicoeur, Paul; de Repentigny, Louis

    2014-10-26

    The tissue-signaling cytokines IL-17 and IL-22 are critical to host defense against oral Candida albicans infection, by their induction of oral antimicrobial peptide expression and recruitment of neutrophils. Mucosal Th17 cells which produce these cytokines are preferentially depleted in HIV-infected patients. Here, we tested the hypothesis that defective IL-17- and IL-22-dependent host responses to C. albicans determine the phenotype of susceptibility to oropharyngeal candidiasis (OPC) in transgenic (Tg) mice expressing HIV-1. Naïve CD4+ T-cells and the differentiated Th1, Th2, Th17, Th1Th17 and Treg lineages were all profoundly depleted in cervical lymph nodes (CLNs) of these Tg mice. However, naive CD4+ cells from Tg mice maintained the capacity to differentiate into these lineages in response to polarizing cytokines in vitro. Expression of Il17, Il22, S100a8 and Ccl20 was enhanced in oral mucosal tissue of non-Tg, but not of Tg mice, after oral infection with C. albicans. Treatment of infected Tg mice with the combination of IL-17 and IL-22, but not IL-17 or Il-22 alone, significantly reduced oral burdens of C. albicans and abundance of Candida hyphae in the epithelium of tongues of infected Tg mice, and restored the ability of the Tg mice to up-regulate expression of S100a8 and Ccl20 in response to C. albicans infection. These findings demonstrate that defective IL-17- and IL-22-dependent induction of innate mucosal immunity to C. albicans is central to the phenotype of susceptibility to OPC in these HIV transgenic mice.

  4. UV-induced mitotic co-segregation of genetic markers in Candida albicans: Evidence for linkage

    International Nuclear Information System (INIS)

    Crandall, M.

    1983-01-01

    Parasexual genetic studies of the medically important yeast Candida albicans were performed using the method of UV-induced mitotic segregation. UV-irradiation of the Hoffmann-La Roche type culture of C. albicans yielded a limited spectrum of mutants at a relatively high fequency. This observation suggested natural heterozygosity. Canavanine-sensitive (CanS) segregants were induced at a frequency of 7.6 . 10 -3 . Double mutants that were both CanS and methionine (Met - ) auxotrophs were induced at a frequency of 7.4 . 10 -3 . The single Met - segregant class was missing indicating linkage. UV-induced CanS or Met - CanS segregants occurred occasionally in twin-sectored colonies. Analyses of the sectors as well as the observed and missing classes of segregants indicated that genes met and can are linked in the cis configuration. The proposed gene order is: centromere - met - can. Thus, it is concluded that the Hoffmann-La Roche strain of C. albicans is naturally heterozygous at two linked loci. These findings are consistent with diploidy. (orig.)

  5. Processing of Candida albicans Ece1p Is Critical for Candidalysin Maturation and Fungal Virulence

    Directory of Open Access Journals (Sweden)

    Jonathan P. Richardson

    2018-01-01

    Full Text Available Candida albicans is an opportunistic fungal pathogen responsible for superficial and life-threatening infections in humans. During mucosal infection, C. albicans undergoes a morphological transition from yeast to invasive filamentous hyphae that secrete candidalysin, a 31-amino-acid peptide toxin required for virulence. Candidalysin damages epithelial cell plasma membranes and stimulates the activating protein 1 (AP-1 transcription factor c-Fos (via p38–mitogen-activated protein kinase [MAPK], and the MAPK phosphatase MKP1 (via extracellular signal-regulated kinases 1 and 2 [ERK1/2]–MAPK, which trigger and regulate proinflammatory cytokine responses, respectively. The candidalysin toxin resides as a discrete cryptic sequence within a larger 271-amino-acid parental preproprotein, Ece1p. Here, we demonstrate that kexin-like proteinases, but not secreted aspartyl proteinases, initiate a two-step posttranslational processing of Ece1p to produce candidalysin. Kex2p-mediated proteolysis of Ece1p after Arg61 and Arg93, but not after other processing sites within Ece1p, is required to generate immature candidalysin from Ece1p, followed by Kex1p-mediated removal of a carboxyl arginine residue to generate mature candidalysin. C. albicans strains harboring mutations of Arg61 and/or Arg93 did not secrete candidalysin, were unable to induce epithelial damage and inflammatory responses in vitro, and showed attenuated virulence in vivo in a murine model of oropharyngeal candidiasis. These observations identify enzymatic processing of C. albicans Ece1p by kexin-like proteinases as crucial steps required for candidalysin production and fungal pathogenicity.

  6. Candida albicans induces Metabolic Reprogramming in human NK cells and responds to Perforin with a Zinc Depletion Response

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    Daniela eHellwig

    2016-05-01

    Full Text Available As part of the innate immune system, natural killer (NK cells are directly involved in the response to fungal infections. Perforin has been identified as the major effector molecule acting against many fungal pathogens. While several studies have shown that perforin mediated fungicidal effects can contribute to fungal clearance, neither the activation of NK cells by fungal pathogens nor the effects of perforin on fungal cells are well understood. In a dual approach, we have studied the global gene expression pattern of primary and cytokine activated NK cells after co-incubation with C. albicans and the transcriptomic adaptation of C. albicans to perforin exposure. NK cells responded to the fungal pathogen with an up-regulation of genes involved in immune signaling and release of cytokines. Furthermore, we observed a pronounced increase of genes involved in glycolysis and glycolysis inhibitor 2-deoxy-D-glucose impaired C. albicans induced NK cell activation. This strongly indicates that metabolic adaptation is a major part of the NK cell response to C. albicans infections. In the fungal pathogen, perforin induced a strong up-regulation of several fungal genes involved in the zinc depletion response, such as PRA1 and ZRT1. These data suggest that fungal zinc homeostasis is linked to the reaction to perforin secreted by NK cells. However, deletion mutants in PRA1 and ZRT1 did not show altered susceptibility to perforin.

  7. Detection of inhibitors of Candida albicans Cdr transporters using a diS-C3(3 fluorescence

    Directory of Open Access Journals (Sweden)

    Joanna eSzczepaniak

    2015-03-01

    Full Text Available Candida albicans is a major cause of opportunistic and life-threatening, systemic fungal infections. Hence new antifungal agents, as well as new methods to treat fungal infections, are still needed. The application of inhibitors of drug-efflux pumps may increase the susceptibility of C. albicans to drugs. We developed a new fluorescence method that allows the in vivo activity evaluation of compounds inhibiting of C. albicans transporters. We show that the potentiometric dye 3,3′-dipropylthiacarbocyanine iodide diS-C3(3 is pumped out by both Cdr1 and Cdr2 transporters. The fluorescence labeling with diS-C3(3 enables a real-time observation of the activity of C. albicans Cdr1 and Cdr2 transporters. We demonstrate that enniatin A and beauvericin show different specificities toward these transporters. Enniatin A inhibits diS-C3(3 efflux by Cdr1 while beauvericin inhibits both Cdr1p and Cdr2p.

  8. The Use of Chitosan to Enhance Photodynamic Inactivation against Candida albicans and Its Drug-Resistant Clinical Isolates

    Directory of Open Access Journals (Sweden)

    Tsuimin Tsai

    2013-04-01

    Full Text Available Drug-resistant Candida infection is a major health concern among immunocompromised patients. Antimicrobial photodynamic inactivation (PDI was introduced as an alternative treatment for local infections. Although Candida (C. has demonstrated susceptibility to PDI, high doses of photosensitizer (PS and light energy are required, which may be harmful to eukaryotic human cells. This study explores the capacity of chitosan, a polycationic biopolymer, to increase the efficacy of PDI against C. albicans, as well as fluconazole-resistant clinical isolates in planktonic or biofilm states. Chitosan was shown to effectively augment the effect of PDI mediated by toluidine blue O (TBO against C. albicans that were incubated with chitosan for 30 min following PDI. Chitosan at concentrations as low as 0.25% eradicated C. albicans; however, without PDI treatment, chitosan alone did not demonstrate significant antimicrobial activity within the 30 min of incubation. These results suggest that chitosan only augmented the fungicidal effect after the cells had been damaged by PDI. Increasing the dosage of chitosan or prolonging the incubation time allowed a reduction in the PDI condition required to completely eradicate C. albicans. These results clearly indicate that combining chitosan with PDI is a promising antimicrobial approach to treat infectious diseases.

  9. Efek Antijamur Minyak Atsiri Jahe Putih Kecil (Zingiber officinale var. Amarum terhadap Candida Albicans

    Directory of Open Access Journals (Sweden)

    Huanny Satriyani

    2015-10-01

    Full Text Available The side effects of many antifungal drugs make it necessary to find an herbal alternative with reduced side effects. Many herbals are knwon to have an antifungal effect, including ginger with its volatile oil composition. However, the specific antifungal effect and optimal concentration of the volatile oil from Zingiber officinale var. amarum against C. albicans is not yet known. This research was done to verify the antifungal effect of Zingiber officinale var. amarum volatile oil on C. albicans, to determine its optimal concentration, and to determine the relation between the volatile oil was provided by water and steam distillation of BALITTRO, Bogor. The colonies were double counted in two steps. First, the volatile oil at concentrations of 100%, 50%, 25%, 12.5%, 6.25%, 3.125%, 1.56% and 0.78% were applied for treatment, wheras in the second step concentrations of 100%, 90%, 80%, 70%, 60%, and 50% were used. In the disk diffusion method, the volatile oil concentrations of 100%, 70%, 60%, 50%, 25%, 12.5%, 6.25% and 3.125% were applied in triplicate in Petri dishes containing C. albicans by using 6 mm blank disks. Result: Mann-Whitney test showed the significant decrease of the colonies between 6.25% and 3.125% of the volatile oil concentration (α = 0.021, and also between the volatile oil concentration 6.25% and the control group (α = 0.014. The Spearman test showed a positive and strong correlation between the volatile oil of Zingiber officinale var. amarum and its inhibition zone (r = 0.91. Conclusion: The volatile oil of Zingiber officinale var. amarum has an antifungal effect against C. albicans with an optimal concentration of 6.25%, and increasing volatile oil concentration is followed by increasing inhibition zone.

  10. Candida albicans ethanol stimulates Pseudomonas aeruginosa WspR-controlled biofilm formation as part of a cyclic relationship involving phenazines.

    Directory of Open Access Journals (Sweden)

    Annie I Chen

    2014-10-01

    Full Text Available In chronic infections, pathogens are often in the presence of other microbial species. For example, Pseudomonas aeruginosa is a common and detrimental lung pathogen in individuals with cystic fibrosis (CF and co-infections with Candida albicans are common. Here, we show that P. aeruginosa biofilm formation and phenazine production were strongly influenced by ethanol produced by the fungus C. albicans. Ethanol stimulated phenotypes that are indicative of increased levels of cyclic-di-GMP (c-di-GMP, and levels of c-di-GMP were 2-fold higher in the presence of ethanol. Through a genetic screen, we found that the diguanylate cyclase WspR was required for ethanol stimulation of c-di-GMP. Multiple lines of evidence indicate that ethanol stimulates WspR signaling through its cognate sensor WspA, and promotes WspR-dependent activation of Pel exopolysaccharide production, which contributes to biofilm maturation. We also found that ethanol stimulation of WspR promoted P. aeruginosa colonization of CF airway epithelial cells. P. aeruginosa production of phenazines occurs both in the CF lung and in culture, and phenazines enhance ethanol production by C. albicans. Using a C. albicans adh1/adh1 mutant with decreased ethanol production, we found that fungal ethanol strongly altered the spectrum of P. aeruginosa phenazines in favor of those that are most effective against fungi. Thus, a feedback cycle comprised of ethanol and phenazines drives this polymicrobial interaction, and these relationships may provide insight into why co-infection with both P. aeruginosa and C. albicans has been associated with worse outcomes in cystic fibrosis.

  11. Acid production by oral strains of Candida albicans and Lactobacilli

    NARCIS (Netherlands)

    Klinke, T.; Kneist, S.; de Soet, J.J.; Kuhlisch, E.; Mauersberger, S.; Forster, A.; Klimm, W.

    2009-01-01

    Both Candida albicans and lactobacilli are common colonizers of carious lesions in children and adolescents. The purpose of this study is to compare the velocity of acid production between C. albicans and several Lactobacillus species at different pH levels and concentrations of glucose. Washed,

  12. Comparison of the adhesion ability of Candida albicans strains to ...

    African Journals Online (AJOL)

    The purpose of the present study is to investigate the ability of oral Candida albicans strains to adhere to Caco-2 and Hep-2 epithelial cells, to produce slime using Congo red and Safranin methods and to form a biofilm on polymethylmethacrylate. A total of 20 C. albicans strains were tested in the present work. The biofilm ...

  13. The effect of submersion denture base acrylic resin in a betel leaf ekstract solution against growth Candida albicans

    Directory of Open Access Journals (Sweden)

    Andi Izham

    2016-06-01

    Full Text Available Denture base is a protesa which replace some or all of the lost original teeth and surrounding tissues. The Pupose of making protesa is for restore the function, appearance, comfort and impaired health result lost teeth. One part of the denture base is base plate. Microorganisms are often found in the oral cavity is Candida albicans (C.albicans approximately 40% in the oral cavity.C.albicans can penetrate the acrylic resin that can infect the soft tissue and is the cause of denture stomatitis therefore the disinfection of denture base is a important factor that must be done. In general betel leaves contant up to 4.2% essential oil compounds and phenyl propanoid and tannin. These compounds is a antimicroba and antifungal which can inhibit the growth of several type of bacteria among others Escherichia coli, Salmonella sp, Staphylococcus aurens, Klebstella, Pasteurella and can turn off the C.albicans. The purpose of the research is to determine how the effect of submersion denture base acrylic resin in a betel leaf ekstract solution against growth C.albicans.Type of research is an experimental laboratory with a longitudinal design (follow-up study. The sampling method used is total sampling. The results showed that the number of C.albicans colonies n denture base acrylic resin which soaked betel leaf extract solution that the dilution 10-1  with consentration 2.5% total colony count is 2 and the results 2.0 x 101 CFU/ml, on a control solution that the dilution 10-2 total colony 355 and the result 3.55 x 104 CFU/ml, that the dilution  10-3 total colony 62 and the result 6.2 x 104 CFU/ml.

  14. Photodynamic inactivation of Candida albicans sensitized by tri- and tetra-cationic porphyrin derivatives.

    Science.gov (United States)

    Cormick, M Paula; Alvarez, M Gabriela; Rovera, Marisa; Durantini, Edgardo N

    2009-04-01

    The photodynamic action of 5-(4-trifluorophenyl)-10,15,20-tris(4-trimethylammoniumphenyl)porphyrin iodide (TFAP(3+)) and 5,10,15,20-tetra(4-N,N,N-trimethylammonium phenyl)porphyrin p-tosylate (TMAP(4+)) has been studied in vitro on Candida albicans. The results of these cationic porphyrins were compared with those of 5,10,15,20-tetra(4-sulphonatophenyl)porphyrin (TPPS(4-)), which characterizes an anionic sensitizer. In vitro investigations show that these cationic porphyrins are rapidly bound to C. albicans cells, reaching a value of approximately 1.4 nmol/10(6) cells, when the cellular suspensions were incubated with 5 microM sensitizer for 30 min. In contrast, TPPS(4-) is poorly uptaken by yeast cells. The fluorescence spectra of these sensitizers into the cells confirm this behaviour. The amount of porphyrin binds to cells is dependent on both sensitizer concentrations (1-5 microM) and cells densities (10(6)-10(8) cells/mL). Photosensitized inactivation of C. albicans cellular suspensions increases with sensitizer concentration, causing a approximately 5 log decrease of cell survival, when the cultures are treated with 5 microM of cationic porphyrin and irradiated for 30 min. However, the photocytotoxicity decreases with an increase in the cell density, according to its low binding to cells. Under these conditions, the photodynamic activity of TFAP(3+) is quite similar to that produced by TMAP(4+), whereas no important inactivation effect was found for TPPS(4)(-). The high photodynamic activity of cationic porphyrins was confirmed by growth delay experiments. Thus, C. albicans cell growth was not detected in the presence of 5 microM TFAP(3+). Photodynamic inactivation capacities of these sensitizers were also evaluated on C. albicans cells growing in colonies on agar surfaces. Cationic porphyrins produce a growth delay of C. albicans colonies and viability of cells was not observed after 3 h irradiation, indicating a complete inactivation of yeast cells

  15. Candida albicans mannans mediate Streptococcus mutans exoenzyme GtfB binding to modulate cross-kingdom biofilm development in vivo.

    Science.gov (United States)

    Hwang, Geelsu; Liu, Yuan; Kim, Dongyeop; Li, Yong; Krysan, Damian J; Koo, Hyun

    2017-06-01

    Candida albicans is frequently detected with heavy infection by Streptococcus mutans in plaque-biofilms from children with early-childhood caries (ECC). This cross-kingdom biofilm contains an extensive matrix of extracellular α-glucans that is produced by an exoenzyme (GtfB) secreted by S. mutans. Here, we report that mannans located on the outer surface of C. albicans cell-wall mediates GtfB binding, enhancing glucan-matrix production and modulating bacterial-fungal association within biofilms formed in vivo. Using single-molecule atomic force microscopy, we determined that GtfB binds with remarkable affinity to mannans and to the C. albicans surface, forming a highly stable and strong bond (1-2 nN). However, GtfB binding properties to C. albicans was compromised in strains defective in O-mannan (pmt4ΔΔ) or N-mannan outer chain (och1ΔΔ). In particular, the binding strength of GtfB on och1ΔΔ strain was severely disrupted (>3-fold reduction vs. parental strain). In turn, the GtfB amount on the fungal surface was significantly reduced, and the ability of C. albicans mutant strains to develop mixed-species biofilms with S. mutans was impaired. This phenotype was independent of hyphae or established fungal-biofilm regulators (EFG1, BCR1). Notably, the mechanical stability of the defective biofilms was weakened, resulting in near complete biomass removal by shear forces. In addition, these in vitro findings were confirmed in vivo using a rodent biofilm model. Specifically, we observed that C. albicans och1ΔΔ was unable to form cross-kingdom biofilms on the tooth surface of rats co-infected with S. mutans. Likewise, co-infection with S. mutans defective in GtfB was also incapable of forming mixed-species biofilms. Taken together, the data support a mechanism whereby S. mutans-secreted GtfB binds to the mannan layer of C. albicans to promote extracellular matrix formation and their co-existence within biofilms. Enhanced understanding of GtfB-Candida interactions

  16. The Candida albicans-specific gene EED1 encodes a key regulator of hyphal extension.

    LENUS (Irish Health Repository)

    Martin, Ronny

    2011-04-01

    The extension of germ tubes into elongated hyphae by Candida albicans is essential for damage of host cells. The C. albicans-specific gene EED1 plays a crucial role in this extension and maintenance of filamentous growth. eed1Δ cells failed to extend germ tubes into long filaments and switched back to yeast growth after 3 h of incubation during growth on plastic surfaces. Expression of EED1 is regulated by the transcription factor Efg1 and ectopic overexpression of EED1 restored filamentation in efg1Δ. Transcriptional profiling of eed1Δ during infection of oral tissue revealed down-regulation of hyphal associated genes including UME6, encoding another key transcriptional factor. Ectopic overexpression of EED1 or UME6 rescued filamentation and damage potential in eed1Δ. Transcriptional profiling during overexpression of UME6 identified subsets of genes regulated by Eed1 or Ume6. These data suggest that Eed1 and Ume6 act in a pathway regulating maintenance of hyphal growth thereby repressing hyphal-to-yeast transition and permitting dissemination of C. albicans within epithelial tissues.

  17. Proper Sterol Distribution Is Required for Candida albicans Hyphal Formation and Virulence

    Science.gov (United States)

    McCourt, Paula; Liu, Hsing-Yin; Parker, Josie E.; Gallo-Ebert, Christina; Donigan, Melissa; Bata, Adam; Giordano, Caroline; Kelly, Steven L.; Nickels, Joseph T.

    2016-01-01

    Candida albicans is an opportunistic fungus responsible for the majority of systemic fungal infections. Multiple factors contribute to C. albicans pathogenicity. C. albicans strains lacking CaArv1 are avirulent. Arv1 has a conserved Arv1 homology domain (AHD) that has a zinc-binding domain containing two cysteine clusters. Here, we explored the role of the CaAHD and zinc-binding motif in CaArv1-dependent virulence. Overall, we found that the CaAHD was necessary but not sufficient for cells to be virulent, whereas the zinc-binding domain was essential, as Caarv1/Caarv1 cells expressing the full-length zinc-binding domain mutants, Caarv1C3S and Caarv1C28S, were avirulent. Phenotypically, we found a direct correlation between the avirulence of Caarv1/Caarv1, Caarrv1AHD, Caarv1C3S, and Caarv1C28S cells and defects in bud site selection, septa formation and localization, and hyphal formation and elongation. Importantly, all avirulent mutant strains lacked the ability to maintain proper sterol distribution. Overall, our results have established the importance of the AHD and zinc-binding domain in fungal invasion, and have correlated an avirulent phenotype with the inability to maintain proper sterol distribution. PMID:27587298

  18. Proper Sterol Distribution Is Required for Candida albicans Hyphal Formation and Virulence

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    Paula McCourt

    2016-11-01

    Full Text Available Candida albicans is an opportunistic fungus responsible for the majority of systemic fungal infections. Multiple factors contribute to C. albicans pathogenicity. C. albicans strains lacking CaArv1 are avirulent. Arv1 has a conserved Arv1 homology domain (AHD that has a zinc-binding domain containing two cysteine clusters. Here, we explored the role of the CaAHD and zinc-binding motif in CaArv1-dependent virulence. Overall, we found that the CaAHD was necessary but not sufficient for cells to be virulent, whereas the zinc-binding domain was essential, as Caarv1/Caarv1 cells expressing the full-length zinc-binding domain mutants, Caarv1C3S and Caarv1C28S, were avirulent. Phenotypically, we found a direct correlation between the avirulence of Caarv1/Caarv1, Caarrv1AHD, Caarv1C3S, and Caarv1C28S cells and defects in bud site selection, septa formation and localization, and hyphal formation and elongation. Importantly, all avirulent mutant strains lacked the ability to maintain proper sterol distribution. Overall, our results have established the importance of the AHD and zinc-binding domain in fungal invasion, and have correlated an avirulent phenotype with the inability to maintain proper sterol distribution.

  19. Biosurfactants prevent in vitro Candida albicans biofilm formation on resins and silicon materials for prosthetic devices.

    Science.gov (United States)

    Cochis, Andrea; Fracchia, Letizia; Martinotti, Maria Giovanna; Rimondini, Lia

    2012-06-01

    The aim of this study was to evaluate in vitro the preventive antiadhesion activity of biosurfactants against Candida albicans biofilm. Disks of silicon and acrylic resin for denture prostheses were precoated with increasing concentrations of biosurfactants obtained from endophyte biofilms selected from Robinia pseudoacacia and from Nerium oleander, and afterward infected with C. albicans cells. The number of biofilm cells were detected by colony-forming unit (CFU) counting, cell viability was established by the 2,3-bis(2-methoxy-4-nitro-5-sulphophenyl)-5-[(phenyl amino)carbonyl]-2H-tetrazolium hydroxide (XTT) assay, and biosurfactant cytotoxicity was evaluated by the [3-(4,5-dimethyliazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphophenyl)-2H-tetrazolium] (MTT) assay. Chlorhexidine was used as control. Precoating with biosurfactants caused a greater reduction (P biosurfactants was observed at low concentrations (78.12 μg/mL and 156.12 μg/mL) which were noncytotoxic. This study demonstrated the preventive antiadhesion activity of biosurfactants against C. albicans biofilm. These agents are amphiphilic, interfere with microbial adhesion, and demonstrate cycompatibility with epithelial cells and fibroblasts. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Candida albicans PROTEIN PROFILE CHANGES IN RESPONSE TO THE BUTANOLIC EXTRACT OF Sapindus saponariaL.

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    Adriana FIORINI

    2016-01-01

    Full Text Available Candida albicans is an opportunistic human pathogen that is capable of causing superficial and systemic infections in immunocompromised patients. Extracts of Sapindus saponaria have been used as antimicrobial agents against various organisms. In the present study, we used a combination of two-dimensional polyacrylamide gel electrophoresis (2D-PAGE and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS to identify the changes in protein abundance of C. albicans after exposure to the minimal inhibitory concentration (MIC and sub-minimal inhibitory concentration (sub-MIC of the butanolic extract (BUTE of S. saponaria and also to fluconazole. A total of six different proteins with greater than 1.5 fold induction or repression relative to the untreated control cells were identified among the three treatments. In general, proteins/enzymes involved with the glycolysis (GPM1, ENO1, FBA1, amino acid metabolism (ILV5, PDC11 and protein synthesis (ASC1 pathways were detected. In conclusion, our findings reveal antifungal-induced changes in protein abundance of C. albicans. By using the previously identified components of the BUTE of S. saponaria(e.g., saponins and sesquiterpene oligoglycosides, it will be possible to compare the behavior of compounds with unknown mechanisms of action, and this knowledge will help to focus the subsequent biochemical work aimed at defining the effects of these compounds.

  1. Characterisation of the Candida albicans Phosphopantetheinyl Transferase Ppt2 as a Potential Antifungal Drug Target.

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    Katharine S Dobb

    Full Text Available Antifungal drugs acting via new mechanisms of action are urgently needed to combat the increasing numbers of severe fungal infections caused by pathogens such as Candida albicans. The phosphopantetheinyl transferase of Aspergillus fumigatus, encoded by the essential gene pptB, has previously been identified as a potential antifungal target. This study investigated the function of its orthologue in C. albicans, PPT2/C1_09480W by placing one allele under the control of the regulatable MET3 promoter, and deleting the remaining allele. The phenotypes of this conditional null mutant showed that, as in A. fumigatus, the gene PPT2 is essential for growth in C. albicans, thus fulfilling one aspect of an efficient antifungal target. The catalytic activity of Ppt2 as a phosphopantetheinyl transferase and the acyl carrier protein Acp1 as a substrate were demonstrated in a fluorescence transfer assay, using recombinant Ppt2 and Acp1 produced and purified from E.coli. A fluorescence polarisation assay amenable to high-throughput screening was also developed. Therefore we have identified Ppt2 as a broad-spectrum novel antifungal target and developed tools to identify inhibitors as potentially new antifungal compounds.

  2. Propolis Is an Efficient Fungicide and Inhibitor of Biofilm Production by Vaginal Candida albicans

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    Isis Regina Grenier Capoci

    2015-01-01

    Full Text Available Vulvovaginal candidiasis (VVC is one of the most common genital infections in women. The therapeutic arsenal remains restricted, and some alternatives to VVC treatment are being studied. The present study evaluated the influence of a propolis extractive solution (PES on biofilm production by Candida albicans isolated from patients with VVC. Susceptibility testing was used to verify the minimum inhibitory concentration (MIC of PES, with fluconazole and nystatin as controls. The biofilm formation of 29 vaginal isolates of C. albicans and a reference strain that were exposed to PES was evaluated using crystal violet staining. Colony-forming units were evaluated, proteins and carbohydrates of the matrix biofilm were quantified, and scanning electron microscopy was performed. The MIC of PES ranged from 68.35 to 546.87 μg/mL of total phenol content in gallic acid. A concentration of 546.87 μg/mL was able to cause the death of 75.8% of the isolates. PES inhibited biofilm formation by C. albicans from VVC. Besides antifungal activity, PES appears to present important antibiofilm activity on abiotic surfaces, indicating that it may have an additional beneficial effect in the treatment of VVC.

  3. Evaluation of Antifungal Activity and Mechanism of Action of Citral against Candida albicans

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    Maria Clerya Alvino Leite

    2014-01-01

    Full Text Available Candida albicans is a yeast that commensally inhabits the human body and can cause opportunistic or pathogenic infections. Objective. To investigate the antifungal activity of citral against C. albicans. Methodology. The minimum inhibitory concentration (MIC and the minimum fungicidal concentration (MFC were determined by the broth microdilution techniques. We also investigated possible citral action on cell walls (0.8 M sorbitol, cell membranes (citral to ergosterol binding, the time-kill curve, and biological activity on the yeast’s morphology. Results. The MIC and MFC of citral were, respectively, 64 µg/mL and 256 µg/mL. Involvement with the cell wall and ergosterol binding were excluded as possible mechanisms of action. In the morphological interference assay, it was observed that the product inhibited pseudohyphae and chlamydoconidia formation. The MIC and the MFC of citral required only 4 hours of exposure to effectively kill 99.9% of the inoculum. Conclusion. Citral showed in vitro antifungal potential against strains of C. albicans. Citral’s mechanism of action does not involve the cell wall or ergosterol, and further study is needed to completely describe its effects before being used in the future as a component of new antifungals.

  4. Effect of Schinus terebinthifolius on Candida albicans growth kinetics, cell wall formation and micromorphology.

    Science.gov (United States)

    Alves, Lívia Araújo; Freires, Irlan de Almeida; Pereira, Tricia Murielly; de Souza, Andrade; Lima, Edeltrudes de Oliveira; de Castro, Ricardo Dias

    2013-01-01

    To evaluate the anti-fungal activity of a tincture from Schinus terebinthifolius (Brazilian pepper tree) on Candida albicans (ATCC 289065), a micro-organism associated with fungal infections of the oral cavity. Minimum Inhibitory Concentration (MIC) and Minimum Fungicidal Concentration (MFC) were determined through microdilution technique, as well as the microbial growth curve of C. albicans promoted by S. terebinthifolius. In addition, this study investigated a possible activity of the product on the fungal cell wall and its biological activity on fungal morphology. Nystatin was used as control and all tests were performed in triplicate. S. terebinthifolius showed MIC of 312.5 µg/mL and MFC of 2500 µg/mL upon the strain tested, while Nystatin showed MIC and MFC of 6.25 µg/mL. As regards the microbial growth curve, S. terebinthifolius was able to significantly reduce the number of CFU/mL when compared to growth control until the time of 60 min. In the times 120 and 180 min there was no statistically significant difference between the growth control and the experimental product. S. terebinthifolius possibly acts on the fungal cell wall, once the sorbitol test indicated a MIC of 1250 µg/mL. In the fungal morphology, a reduction was observed of pseudo-hyphae, chlamydoconidia and blastoconidia in the presence of the experimental product. S. terebinthifolius showed anti-fungal activity against C. albicans, inhibiting, probably, the fungal cell wall formation.

  5. A relay network of extracellular heme-binding proteins drives C. albicans iron acquisition from hemoglobin.

    Science.gov (United States)

    Kuznets, Galit; Vigonsky, Elena; Weissman, Ziva; Lalli, Daniela; Gildor, Tsvia; Kauffman, Sarah J; Turano, Paola; Becker, Jeffrey; Lewinson, Oded; Kornitzer, Daniel

    2014-10-01

    Iron scavenging constitutes a crucial challenge for survival of pathogenic microorganisms in the iron-poor host environment. Candida albicans, like many microbial pathogens, is able to utilize iron from hemoglobin, the largest iron pool in the host's body. Rbt5 is an extracellular glycosylphosphatidylinositol (GPI)-anchored heme-binding protein of the CFEM family that facilitates heme-iron uptake by an unknown mechanism. Here, we characterize an additional C. albicans CFEM protein gene, PGA7, deletion of which elicits a more severe heme-iron utilization phenotype than deletion of RBT5. The virulence of the pga7-/- mutant is reduced in a mouse model of systemic infection, consistent with a requirement for heme-iron utilization for C. albicans pathogenicity. The Pga7 and Rbt5 proteins exhibit distinct cell wall attachment, and discrete localization within the cell envelope, with Rbt5 being more exposed than Pga7. Both proteins are shown here to efficiently extract heme from hemoglobin. Surprisingly, while Pga7 has a higher affinity for heme in vitro, we find that heme transfer can occur bi-directionally between Pga7 and Rbt5, supporting a model in which they cooperate in a heme-acquisition relay. Together, our data delineate the roles of Pga7 and Rbt5 in a cell surface protein network that transfers heme from extracellular hemoglobin to the endocytic pathway, and provide a paradigm for how receptors embedded in the cell wall matrix can mediate nutrient uptake across the fungal cell envelope.

  6. Randomized, Double-Blind, Placebo-Controlled Study on Decolonization Procedures for Methicillin-Resistant Staphylococcus aureus (MRSA among HIV-Infected Adults.

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    Amy Weintrob

    Full Text Available HIV-infected persons have increased risk of MRSA colonization and skin and soft-tissue infections (SSTI. However, no large clinical trial has examined the utility of decolonization procedures in reducing MRSA colonization or infection among community-dwelling HIV-infected persons.550 HIV-infected adults at four geographically diverse US military HIV clinics were prospectively screened for MRSA colonization at five body locations every 6 months during a 2-year period. Those colonized were randomized in a double-blind fashion to nasal mupirocin (Bactroban twice daily and hexachlorophene (pHisoHex soaps daily for 7 days compared to placeboes similar in appearance but without specific antibacterial activity. The primary endpoint was MRSA colonization at 6-months post-randomization; secondary endpoints were time to MRSA clearance, subsequent MRSA infections/SSTI, and predictors for MRSA clearance at the 6-month time point.Forty-nine (9% HIV-infected persons were MRSA colonized and randomized. Among those with 6-month colonization data (80% of those randomized, 67% were negative for MRSA colonization in both groups (p = 1.0. Analyses accounting for missing 6-month data showed no significant differences could have been achieved. In the multivariate adjusted models, randomization group was not associated with 6-month MRSA clearance. The median time to MRSA clearance was similar in the treatment vs. placebo groups (1.4 vs. 1.8 months, p = 0.35. There was no difference on subsequent development of MRSA infections/SSTI (p = 0.89. In a multivariable model, treatment group, demographics, and HIV-specific factors were not predictive of MRSA clearance at the 6-month time point.A one-week decolonization procedure had no effect on MRSA colonization at the 6-month time point or subsequent infection rates among community-dwelling HIV-infected persons. More aggressive or novel interventions may be needed to reduce the burden of MRSA in this population

  7. Effects of albendazole on the clinical outcome and immunological responses in helminth co-infected tuberculosis patients: a double blind randomised clinical trial.

    Science.gov (United States)

    Abate, E; Elias, D; Getachew, A; Alemu, S; Diro, E; Britton, S; Aseffa, A; Stendahl, O; Schön, T

    2015-02-01

    Despite several review papers and experimental studies concerning the impact of chronic helminth infection on tuberculosis in recent years, there is a scarcity of data from clinical field studies in highly endemic areas for these diseases. We believe this is the first randomised clinical trial investigating the impact of albendazole treatment on the clinical and immunological outcomes of helminth co-infected tuberculosis patients. A randomised, double-blind, placebo-controlled trial of albendazole (400mg per day for 3 days) in helminth-positive tuberculosis patients was conducted in Gondar, Ethiopia. The primary outcome was clinical improvement (ΔTB score) after 2 months. Among secondary outcomes were changes in the levels of eosinophils, CD4+ T cells, regulatory T cells, IFN-γ, IL-5 and IL-10 after 3 months. A total of 140 helminth co-infected tuberculosis patients were included with an HIV co-infection rate of 22.8%. There was no significant effect on the primary outcome (ΔTB score: 5.6±2.9 for albendazole versus 5.9±2.5 for placebo, P=0.59). The albendazole-treated group showed a decline in eosinophil cells (P=0.001) and IL-10 (P=0.017) after 3 months. In an exploratory analysis after 12 weeks, the albendazole treated group showed a trend towards weight gain compared with the placebo group (11.2±8.5 kg versus 8.2±8.7 kg, P=0.08)). The reductions in eosinophil counts and IL-10 show that asymptomatic helminth infection significantly affects host immunity during tuberculosis and can be effectively reversed by albendazole treatment. The clinical effects of helminth infection on chronic infectious diseases such as tuberculosis merit further characterisation. Copyright © 2014 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

  8. A double labeling technique for performing immunocytochemistry and in situ hybridization in virus infected cell cultures and tissues

    International Nuclear Information System (INIS)

    Gendelman, H.E.; Moench, T.R.; Narayan, O.; Griffin, D.E.; Clements, J.E.

    1985-01-01

    This report describes a combined immunocytochemical and in situ hybridization procedure which allows visualization of cellular or viral antigens and viral RNA in the same cell. Cultures infected with visna or measles virus were fixed in periodate-lysine-paraformaldehyde-glutaraldehyde, stained by the avidin-biotin-peroxidase technique using antibodies to viral or cellular proteins and then incubated with radiolabeled specific DNA probes (in situ hybridization). This technique provides a new approach to the study of viral pathogenesis by: (1) identifying the types of cells which are infected in the host and (2) identifying points of blockade in the virus life cycle during persistent infections. (Auth.)

  9. [Therapeutic effect of double fill nine tastes soup in treating recurrent respiratory infection (RRI) and change of immune function in children].

    Science.gov (United States)

    Wang, Youcheng; Zhang, Lijuan; Hu, Guohua; Wang, Menghe; Tang, Xiaoyuan; Guo, Hui; Shi, Yimei; Chen, Shufang; Shi, Changchun

    2012-04-01

    To investigate the therapeutic effect of double fill nine tastes soup in treating children recurrent respiratory infection (RRTI) and the change of immune function. 77 RRTI patients were randomly selected into observation and control groups. The observation group was treated with Chinese medicine- double fill nine tastes soup,water frying points 2 times oral. The control was treated with transfer factor oral liquid,every 10 mL,2 times daily oral. Treatment periods were both two months. IgA, IgG, IgM and IL-12, TNF-alpha, INF-gamma were detected before and after treatment to assess the clinical effects and the changes of immune factors, meanwhile, a health group was established. Before treatment, compared with the health group, the serum IgA, IgG, IgM, IgE, IL-12, TNF-alpha, IFN-gamma in both groups were significantly different (P soup has significant effects in treating recurrent respiratory infection (RRI) and enhance the immune function in children.

  10. Probiotic lactobacillus and estrogen effects on vaginal epithelial gene expression responses to Candida albicans.

    Science.gov (United States)

    Wagner, R Doug; Johnson, Shemedia J

    2012-06-20

    Vaginal epithelial cells have receptors, signal transduction mechanisms, and cytokine secretion capabilities to recruit host defenses against Candida albicans infections. This research evaluates how probiotic lactobacilli affect the defensive epithelial response. This study used quantitative reverse transcription-polymerase chain reaction assay (qRT-PCR), flow cytometry, and a multiplex immunoassay to observe changes in the regulation of gene expression related to cytokine responses in the VK2 (E6/E7) vaginal epithelial cell line treated with 17β-estradiol, exposed to probiotic Lactobacillus rhamnosus GR-1® and Lactobacillus reuteri RC-14® and challenged with C. albicans. Data were statistically evaluated by repeated measures analysis of variance and paired t-tests where appropriate. C. albicans induced mRNA expression of genes related to inflammatory cytokine responses associated with nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signal transduction pathways. 17β-estradiol suppressed expression of interleukin-1α (IL-1α), IL-6, IL-8, and tumor necrosis factor alpha (TNFα) mRNA. Probiotic lactobacilli suppressed C. albicans-induced nuclear factor-kappa B inhibitor kinase kinase alpha (Iκκα), Toll-like receptor-2 (TLR2), TLR6, IL-8, and TNFα, also suggesting inhibition of NF-κB signaling. The lactobacilli induced expression of IL-1α, and IL-1β mRNA, which was not inhibited by curcumin, suggesting that they induce an alternate inflammatory signal transduction pathway to NF-κB, such as the mitogen activated protein kinase and activator protein-1 (MAPK/AP-1) signal transduction pathway. Curcumin inhibited IL-13 secretion, suggesting that expression of this cytokine is mainly regulated by NF-κB signaling in VK2 cells. The results suggest that C. albicans infection induces pro-inflammatory responses in vaginal epithelial cells, and estrogen and lactobacilli suppress expression of NF-κB-related inflammatory genes. Probiotic

  11. Differential filamentation of Candida albicans and Candida dubliniensis Is governed by nutrient regulation of UME6 expression.

    LENUS (Irish Health Repository)

    O'Connor, Leanne

    2010-09-01

    Candida dubliniensis is closely related to Candida albicans; however, it is responsible for fewer infections in humans and is less virulent in animal models of infection. C. dubliniensis forms fewer hyphae in vivo, and this may contribute to its reduced virulence. In this study we show that, unlike C. albicans, C. dubliniensis fails to form hyphae in yeast extract-peptone-dextrose (YPD) medium supplemented with 10% (vol\\/vol) fetal calf serum (YPDS medium). However, C. dubliniensis filaments in water plus 10% (vol\\/vol) fetal calf serum (WS), and this filamentation is inhibited by the addition of peptone and glucose. Repression of filamentation in YPDS medium could be partly overcome by preculture in synthetic Lee\\'s medium. Unlike C. albicans, inoculation of C. dubliniensis in YPDS medium did not result in increased UME6 transcription. However, >100-fold induction of UME6 was observed when C. dubliniensis was inoculated in nutrient-poor WS medium. The addition of increasing concentrations of peptone to WS medium had a dose-dependent effect on reducing UME6 expression. Transcript profiling of C. dubliniensis hyphae in WS medium identified a starvation response involving expression of genes in the glyoxylate cycle and fatty acid oxidation. In addition, a core, shared transcriptional response with C. albicans could be identified, including expression of virulence-associated genes including SAP456, SAP7, HWP1, and SOD5. Preculture in nutrient-limiting medium enhanced adherence of C. dubliniensis, epithelial invasion, and survival following coculture with murine macrophages. In conclusion, C. albicans, unlike C. dubliniensis, appears to form hyphae in liquid medium regardless of nutrient availability, which may account for its increased capacity to cause disease in humans.

  12. Effects of long-term weekly iron and folic acid supplementation on lower genital tract infection - a double blind, randomised controlled trial in Burkina Faso.

    Science.gov (United States)

    Brabin, Loretta; Roberts, Stephen A; Gies, Sabine; Nelson, Andrew; Diallo, Salou; Stewart, Christopher J; Kazienga, Adama; Birtles, Julia; Ouedraogo, Sayouba; Claeys, Yves; Tinto, Halidou; d'Alessandro, Umberto; Faragher, E Brian; Brabin, Bernard

    2017-11-23

    Provision of routine iron supplements to prevent anaemia could increase the risk for lower genital tract infections as virulence of some pathogens depends on iron availability. This trial in Burkina Faso assessed whether weekly periconceptional iron supplementation increased the risk of lower genital tract infection in young non-pregnant and pregnant women. Genital tract infections were assessed within a double blind, controlled, non-inferiority trial of malaria risk among nulliparous women, randomised to receive either iron and folic acid or folic acid alone, weekly, under direct observation for 18 months. Women conceiving during this period entered the pregnancy cohort. End assessment (FIN) for women remaining non-pregnant was at 18 months. For the pregnancy cohort, end assessment was at the first scheduled antenatal visit (ANC1). Infection markers included Nugent scores for abnormal flora and bacterial vaginosis (BV), T. vaginalis PCR, vaginal microbiota, reported signs and symptoms, and antibiotic and anti-fungal prescriptions. Iron biomarkers were assessed at baseline, FIN and ANC1. Analysis compared outcomes by intention to treat and in iron replete/deficient categories. A total of 1954 women (mean 16.8 years) were followed and 478 (24.5%) became pregnant. Median supplement adherence was 79% (IQR 59-90%). Baseline BV prevalence was 12.3%. At FIN and ANC1 prevalence was 12.8% and 7.0%, respectively (P Iron-supplemented non-pregnant women received more antibiotic treatments for non-genital infections (P = 0.014; mainly gastrointestinal infections (P = 0.005), anti-fungal treatments for genital infections (P = 0.014) and analgesics (P = 0.008). Weekly iron did not significantly reduce iron deficiency prevalence. At baseline, iron-deficient women were more likely to have normal vaginal flora (P = 0.016). Periconceptional weekly iron supplementation of young women did not increase the risk of lower genital tract infections but did increase

  13. Prevention of Cardiac Implantable Electronic Device Infections: Single Operator Technique with Use of Povidone-Iodine, Double Gloving, Meticulous Aseptic/Antiseptic Measures and Antibiotic Prophylaxis.

    Science.gov (United States)

    Manolis, Antonis S; Melita, Helen

    2017-01-01

    Cardiac implantable electronic device (CIED) implantation is complicated by infection still at a worrisome rate of 2-5%. Since early on during device implantation procedures, we have adopted an infection-preventive technique which has hitherto resulted in effective prevention of infections. Herein we present our results of applying this technique by a single operator in a prospective series of 762 consecutive patients undergoing device implantation. A meticulous search for and treatment of active, occult, or smoldering infection was undertaken preoperatively. An aseptic/antiseptic technique was used for implantation of each device. Skin preparation is thorough with initial cleansing performed with alcohol followed by povidone-iodine 10% solution, which is also used in the wound and inside the pocket. In addition, we routinely use double gloving, and IV antibiotic prophylaxis 1 hour before and for 48 hours afterwards followed by oral antibiotic for 2-3 days after discharge. The skin is closed with absorbable sutures. The study includes 382 patients having a new pacemaker (n = 333) or battery change, system upgrade or lead revision (n = 49), and 380 patients having a new implantable cardioverter-defibrillator (ICD) (n = 296) or device replacement/upgrade/lead revision (n = 84). The pacemaker group, aged 70.2 ± 16.5 years, includes 18% VVI, 49% DDD, 29% VDD, and 4% cardiac resynchronization therapy (CRT) devices. The ICD group, aged 61.3 ± 13.0 years, with a mean ejection fraction of 36 ± 13%, includes 325 ICD and 55 CRT implants. Over 26.6 ± 33.4 months for the pacemaker group and 36.6 ± 38.3 months for the ICD group, infection occurred in one patient in each group (0.26%) having a device replacement. A consistent and strict approach of aseptic/antiseptic technique with the use of double gloving and povidone-iodine solution within the pocket plus a 4-day regimen of antibiotic prophylaxis minimizes infections in CIED implants. © 2016 Wiley Periodicals, Inc.

  14. Secondary omental and pectoralis major double flap reconstruction following aggressive sternectomy for deep sternal wound infections after cardiac surgery

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    Shirasawa Bungo

    2011-04-01

    Full Text Available Abstract Background Deep sternal wound infection after cardiac surgery carries high morbidity and mortality. Our strategy for deep sternal wound infection is aggressive strenal debridement followed by vacuum-assisted closure (VAC therapy and omental-muscle flap reconstrucion. We describe this strategy and examine the outcome and long-term quality of life (QOL it achieves. Methods We retrospectively examined 16 patients treated for deep sternal wound infection between 2001 and 2007. The most recent nine patients were treated with total sternal resection followed by VAC therapy and secondary closure with omental-muscle flap reconstruction (recent group; whereas the former seven patients were treated with sternal preservation if possible, without VAC therapy, and four of these patients underwent primary closure (former group. We assessed long-term quality of life after DSWI by using the Short Form 36-Item Health Survey, Version 2 (SF36v2. Results One patient died and four required further surgery for recurrence of deep sternal wound infection in the former group. The duration of treatment for deep sternal wound infection in the recent group was significantly shorter than that in previous group (63.4 ± 54.1 days vs. 120.0 ± 31.8 days, respectively; p = 0.039. Despite aggressive sternal resection, the QOL of patients treated for DSWI was only minimally compromised compared with age-, sex-, surgical procedures-matched patients without deep sternal wound infection. Conclusions Aggressive sternal debridement followed by VAC therapy and secondary closure with an omental-muscle flap is effective for deep sternal wound infection. In this series, it resulted in a lower incidence of recurrent infection, shorter hospitalization, and it did not compromise long-term QOL greatly.

  15. AI-2 of Aggregatibacter actinomycetemcomitans Inhibits Candida albicans Biofilm Formation

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    Endang W. Bachtiar

    2014-07-01

    Full Text Available Aggregatibacter actinomycetemcomitans, a Gram-negative bacterium, and Candida albicans, a polymorphic fungus, are both commensals of the oral cavity but both are opportunistic pathogens that can cause oral diseases. A. actinomycetemcomitans produces a quorum-sensing molecule called autoinducer-2 (AI-2, synthesized by LuxS, that plays an important role in expression of virulence factors, in intra- but also in interspecies communication. The aim of this study was to investigate the role of AI-2 based signaling in the interactions between C. albicans and A. actinomycetemcomitans. A. actinomycetemcomitans adhered to C. albicans and inhibited biofilm formation by means of a molecule that was secreted during growth. C. albicans biofilm formation increased significantly when co-cultured with A. actinomycetemcomitans luxS, lacking AI-2 production. Addition of wild-type-derived spent medium or synthetic AI-2 to spent medium of the luxS strain, restored inhibition of C. albicans biofilm formation to wild-type levels. Addition of synthetic AI-2 significantly inhibited hypha formation of C. albicans possibly explaining the inhibition of biofilm formation. AI-2 of A. actinomycetemcomitans is synthesized by LuxS, accumulates during growth and inhibits C. albicans hypha- and biofilm formation. Identifying the molecular mechanisms underlying the interaction between bacteria and fungi may provide important insight into the balance within complex oral microbial communities.

  16. Frequency of Candidiasis and Colonization of Candida albicans in Relation to Oral Contraceptive Pills.

    Science.gov (United States)

    Aminzadeh, Atousa; Sabeti Sanat, Ali; Nik Akhtar, Saeed

    2016-10-01

    Candidiasis, the infection caused by Candida albicans , is one of the most common infections of the oral cavity in humans. Candidiasis causes irritation and is known for its carcinogenic effects. Thus, it is important to recognize the predisposing factors for this opportunistic infection. Several previous studies have demonstrated an increased frequency of vaginal candidiasis in relation to oral contraceptive consumption. Only a few studies on the relation between oral contraceptives and oral candidiasis have been previously conducted. This study aims to evaluate the possible relation between oral contraceptive pills and oral candidiasis. This analytic, case-control study included 40 non-pregnant women divided into two groups: 20 who used oral contraceptive pills and 20 who did not. The groups were matched according to age, oral health, and past and present medical history. Samples were collected from the tongue's dorsum using a cotton swab and inoculated on CHROMagar culture plates. The frequency of positive cultures and the number of Candida colonies were compared between the two groups using independent t-tests and Mann-Whitney statistical tests with SPSS18 software. The frequency of positive cultures of Candida albicans was higher (P value = 0.03) for the case group. Also, the number of C. albicans and C. krusei was significantly higher for the case group compared to the control group (P value = 0.04, P value = 0.03). The results of the present study demonstrate that oral contraceptives containing estradiol can lead to Candida colonization in the oral cavity. It is recommended that further studies comparing the influence of oral contraceptives on Candida's adherence to the epithelium is highly recommended.

  17. Effect of oral antiseptic agents on phospholipase and proteinase enzymes of Candida albicans.

    Science.gov (United States)

    Uygun-Can, Banu; Kadir, Tanju; Gumru, Birsay

    2016-02-01

    Candida-associated denture stomatitis is the most prevalent form of oral candida infections among the denture wearers. Generally, antiseptic oral rinses used in the treatment of these infections are considered as an adjunct or alternative antifungal treatment. Studies have suggested that the intraoral concentrations of antiseptics decrease substantially to the sub-therapeutic levels on account of the dynamics of the oral cavity. This condition yields the question about the minimum antiseptic concentration that effect the character or pathogenesis of Candida during treatment. The extracellular phospholipase and proteinase enzymes of Candida albicans are regarded to have a crucial role in the pathogenesis of human fungal infections. Therefore, the aim of this study was to investigate the effect of different sub-therapeutic concentrations of chlorhexidine gluconate, hexetidine and triclosan on the production of these enzymes by C. albicans strains isolated from 20 patients with denture stomatitis. Phospholipase test was done by using Sabouraud dextrose agar with egg yolk, proteinase test was done by using bovine serum albumin agar. Phospholipase test was done by using Sabouraud dextrose agar with egg yolk, proteinase test was done by using bovine serum albumin agar. Exoenzyme production of 20 strains which were brief exposured to sub-therapeutic concentrations of three antiseptic agents decreased significantly compared with the strains that were not exposured with antiseptic values (pantiseptics (pantiseptic was compared, there were no significant differences between enzymatic activities (p>0.05). The results of this study show that sub-therapeutic levels of each antiseptic may modulate candidal exoenzyme production, consequently suppressing pathogenicity of C. albicans. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Symbiotic Relationship between Streptococcus mutans and Candida albicans Synergizes Virulence of Plaque Biofilms In Vivo

    Science.gov (United States)

    Falsetta, Megan L.; Klein, Marlise I.; Colonne, Punsiri M.; Scott-Anne, Kathleen; Gregoire, Stacy; Pai, Chia-Hua; Gonzalez-Begne, Mireya; Watson, Gene; Krysan, Damian J.; Bowen, William H.

    2014-01-01

    Streptococcus mutans is often cited as the main bacterial pathogen in dental caries, particularly in early-childhood caries (ECC). S. mutans may not act alone; Candida albicans cells are frequently detected along with heavy infection by S. mutans in plaque biofilms from ECC-affected children. It remains to be elucidated whether this association is involved in the enhancement of biofilm virulence. We showed that the ability of these organisms together to form biofilms is enhanced in vitro and in vivo. The presence of C. albicans augments the production of exopolysaccharides (EPS), such that cospecies biofilms accrue more biomass and harbor more viable S. mutans cells than single-species biofilms. The resulting 3-dimensional biofilm architecture displays sizeable S. mutans microcolonies surrounded by fungal cells, which are enmeshed in a dense EPS-rich matrix. Using a rodent model, we explored the implications of this cross-kingdom interaction for the pathogenesis of dental caries. Coinfected animals displayed higher levels of infection and microbial carriage within plaque biofilms than animals infected with either species alone. Furthermore, coinfection synergistically enhanced biofilm virulence, leading to aggressive onset of the disease with rampant carious lesions. Our in vitro data also revealed that glucosyltransferase-derived EPS is a key mediator of cospecies biofilm development and that coexistence with C. albicans induces the expression of virulence genes in S. mutans (e.g., gtfB, fabM). We also found that Candida-derived β1,3-glucans contribute to the EPS matrix structure, while fungal mannan and β-glucan provide sites for GtfB binding and activity. Altogether, we demonstrate a novel mutualistic bacterium-fungus relationship that occurs at a clinically relevant site to amplify the severity of a ubiquitous infectious disease. PMID:24566629

  19. Evaluation of Susceptibility of Strains of Candida Albicans Isolated from AIDS Patients to Fluconazole and Determination of CDR2 Resistance Gene in Resistant Strains by RT-PCR Method

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    E Farahbakhsh

    2011-08-01

    Full Text Available Introduction & Objective: Nowadays, opportunistic fungi especially Candida albicans are the most common cause of life-threatening infections in immunodeficiency patients. Increasing Azole-resistant strains of C.albicans are a main problem in human immunodeficiency virus-infected patients. The aim of this study was to evaluate the CDR2 gene in C.albicans azole resistant strains, isolated from AIDS patients with oropharyngeal candidiasis by RT-PCR method. Materials & Methods: The present experimental study was conducted at Tarbiat Modares University of Medical Sciences in 2009. C. albicans isolates from HIV infected patients were identified by standard procedures, including germ tube formation, clamidospor and color of colonies on CHROM agar. At first, susceptibility of C. albicans isolates was assessed by disk diffusion agar technique. Then, CDR2 resistance gene was analyzed by RT-PCR and electrophoresis of the PCR products. Finally, patterns of the resulted bands were compared with standard fluconazole resistant strains. The collected data was analyzed using the SPSS software. Results: The results of drug sensitivity of 66 C. albicans isolates from AIDS patients revealed that 62.6% were susceptible, 8.6% were susceptible-dose dependent (SDD and 28.7% were resistant. In RT-PCR analysis, 6% of patients had the CDR2 gene. Conclusion: The use of phenotypic methods like disk diffusion agar, which is cheaper, along with genotypic methods, like RT-PCR, which provide the possibility of studying the mechanism of drug resistance, is recommended.

  20. Genotypes of Candida albicans involved in development of candidiasis and their distribution in oral cavity of non-candidiasis individuals.

    Science.gov (United States)

    Takagi, Yuki; Hattori, Hisao; Adachi, Hidesada; Takakura, Shunji; Horii, Toshinobu; Chindamporn, Ariya; Kitai, Hiroki; Tanaka, Reiko; Yaguchi, Takashi; Fukano, Hideo; Kawamoto, Fumihiko; Shimozato, Kazuo; Kanbe, Toshio

    2011-01-01

    Genotype characteristics and distribution of commensal Candida albicans should be studied to predict the development of candidiasis, however, extensive genotype analysis of commensal C. albicans has not been made. In this study, 508 C. albicans isolates were collected from patients with/without candidiasis and divided into 4 isolate groups (SG-1, oral cavity of non-candidiasis patients; SG-2, patients with cutaneous candidiasis; SG-3, patients with vaginal candidiasis; SG-4, patients with candidemia). These isolates were characterized to study the relationship between genotypes and pathogenicity using microsatellite analysis. Using CDC3 and CAI, 5 genotypes (I, 111: 115/33: 41; II, 115: 119/23: 23; III, 115: 123/18: 27; IV, 115: 123/33: 40; and V, 123: 127/32: 41) were found in 4.2%, 8.9%, 7.1%, 2.2% and 3.1% of the isolates, respectively. Genotypes II and III were commonly found in all isolate groups. These genotypes were further divided into 28 types by additional HIS3 and CAIII microsatellite markers. In this analysis, C. albicans with type 6 and type 23 was widely distributed as a commensal species in the oral cavity of non-candidiasis patients and found to be related with candidiasis development. Additionally, genotypes I and IV were found in SG-2 and/or SG-4, suggesting that the fungus with those genotypes is also involved in this development. In contrast, genotype V was not identified in any infective isolates.

  1. Identification of inhibitors of yeast-to-hyphae transition in Candida albicans by a reporter screening assay.

    Science.gov (United States)

    Heintz-Buschart, Anna; Eickhoff, Holger; Hohn, Erwin; Bilitewski, Ursula

    2013-03-10

    Candida albicans is one of the most common opportunistic fungal pathogens, causing life-threatening disease in immunocompromised patients. As it is not primarily a pathogen, but can exist in a commensal state, we aimed at the identification of new anti-infective compounds which do not eradicate the fungus, but primarily disable a virulence determinant. The yeast–hyphae-dimorphism of C. albicans is considered a major contributor to fungal disease, as mutants locked into either yeast or hyphal state have been shown to be less virulent in the mouse-model. We devised a high-throughput screening procedure which allows us to find inhibitors of the induction of hyphae. Hyphae-formation was induced by nitrogen starvation at 37 °C and neutral pH in a reporter strain, which couples promoter activity of the hyphae-specific HWP1 to β-galactosidase expression. In a pilot screening of 720 novel synthetic compounds, we identified substances which inhibited the outgrowth of germ tubes. They belonged to chemical classes not yet known for antimycotic properties, namely methyl aryl-oxazoline carboxylates, dihydrobenzo[d]isoxazolones and thiazolo[4,5-e]benzoisoxazoles. In conclusion we developed a novel screening assay, which addresses the morphological switch from the yeast form of C. albicans to its hyphal form and identified novel chemical structures with activity against C. albicans. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Supramolecular Chitosan Micro-Platelets Synergistically Enhance Anti-Candida albicans Activity of Amphotericin B Using an Immunocompetent Murine Model.

    Science.gov (United States)

    Grisin, Tiphany; Bories, Christian; Bombardi, Martina; Loiseau, Philippe M; Rouffiac, Valérie; Solgadi, Audrey; Mallet, Jean-Maurice; Ponchel, Gilles; Bouchemal, Kawthar

    2017-05-01

    The aim of this work is to design new chitosan conjugates able to self-organize in aqueous solution in the form of micrometer-size platelets. When mixed with amphotericin B deoxycholate (AmB-DOC), micro-platelets act as a drug booster allowing further improvement in AmB-DOC anti-Candida albicans activity. Micro-platelets were obtained by mixing oleoyl chitosan and α-cyclodextrin in water. The formulation is specifically-engineered for mucosal application by dispersing chitosan micro-platelets into thermosensitive pluronic ® F127 20 wt% hydrogel. The formulation completely cured C. albicans vaginal infection in mice and had a superior activity in comparison with AmB-DOC without addition of chitosan micro-platelets. In vitro studies showed that the platelets significantly enhance AmB-DOC antifungal activity since the IC 50 and the MIC 90 decrease 4.5 and 4.8-times. Calculation of fractional inhibitory concentration index (FICI = 0.198) showed that chitosan micro-platelets act in a synergistic way with AmB-DOC against C. albicans. No synergy is found between spherical nanoparticles composed poly(isobutylcyanoacrylate)/chitosan and AmB-DOC. These results demonstrate for the first time the ability of flattened chitosan micro-platelets to have synergistic activity with AmB-DOC against C. albicans candidiasis and highlight the importance of rheological and mucoadhesive behaviors of hydrogels in the efficacy of the treatment.

  3. Molecular analysis and dimorphism of azole-susceptible and resistant Candida albicans isolates Análise molecular e dimorfismo de isolados de Candida albicans suscetíveis e resistentes aos azólicos

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    Carolina Rodrigues Costa

    2011-12-01

    Full Text Available INTRODUCTION: Candida albicans is responsible for superficial or systemic infections known as candidiasis, which may be found in infected tissue as unicellular budding yeasts, hyphae, or pseudohyphae. In this study, the effects of both fluconazole and itraconazole antifungal agents on the hyphal formation and genotypic characterization of C. albicans isolates classified as either susceptible or resistant were investigated. METHODS: The hyphal production of five C. albicans isolates under the action of antifungal agents was investigated by culturing yeast on growth medium and on hyphal induction medium. The genotypic characterization was carried out for 13 isolates of C. albicans using the random amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR method. RESULTS: The dimorphism analysis showed that the hyphal formation was higher in resistant than in the susceptible isolates to both azoles. The RAPD-PCR method identified the formation of two different groups. In group A, four resistant and two susceptible isolates were clustered, and in group B, one resistant and six susceptible isolates were clustered. CONCLUSIONS: Considering that hyphal formation was higher in resistant isolates in the presence of azole drugs, we confirmed that the hyphal production is closely related to susceptibility to azoles. These drugs may affect the morphogenesis of C. albicans depending on their susceptibility to these drugs. In relation to RAPD-PCR, most resistant isolates classified in group A and susceptible isolates in group B demonstrated that this method presented a similar standard between the two groups, suggesting that by this technique, a strong correlation between genotypes and fluconazole-resistant samples may be found.INTRODUÇÃO: Candida albicans é responsável por infecções superficiais ou sistêmicas conhecidas como candidíase, encontrada em tecidos infectados na forma de leveduras brotantes unicelulares, hifas ou pseudohifas. Neste

  4. Penicillenols from a deep-sea fungus Aspergillus restrictus inhibit Candida albicans biofilm formation and hyphal growth.

    Science.gov (United States)

    Wang, Jie; Yao, Qi-Feng; Amin, Muhammad; Nong, Xu-Hua; Zhang, Xiao-Yong; Qi, Shu-Hua

    2017-06-01

    Penicillenols (A1, A2, B1, B2, C1 and C2) were isolated from Aspergillus restrictus DFFSCS006, and could differentially inhibit biofilm formation and eradicate pre-developed biofilms of Candida albicans. Their structure-bioactivity relationships suggested that the saturation of hydrocarbon chain at C-8, R-configuration of C-5 and trans-configuration of the double bond between C-5 and C-6 of pyrrolidine-2,4-dione unit were important for their anti-biofilm activities. Penicillenols A2 and B1 slowed the hyphal growth and suppressed the transcripts of hypha specific genes HWP1, ALS1, ALS3, ECE1 and SAP4. Moreover, penicillenols A2 and B1 were found to act synergistically with amphotericin B against C. albicans biofilm formation.

  5. Perioperative synbiotics administration decreases postoperative infections in patients with colorectal cancer: a randomized, double-blind clinical trial

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    ALINE TABORDA FLESCH

    Full Text Available ABSTRACT Objective: to evaluate the effect of perioperative administration of symbiotics on the incidence of surgical wound infection in patients undergoing surgery for colorectal cancer. Methods: We conducted a randomized clinical trial with colorectal cancer patients undergoing elective surgery, randomly assigned to receive symbiotics or placebo for five days prior to the surgical procedure and for 14 days after surgery. We studied 91 patients, 49 in the symbiotics group (Lactobacillus acidophilus 108 to 109 CFU, Lactobacillus rhamnosus 108 to 109 CFU, Lactobacillus casei 108 to 109 CFU, Bifi dobacterium 108 to 109 CFU and fructo-oligosaccharide (FOS 6g and 42 in the placebo group. Results: surgical site infection occurred in one (2% patient in the symbiotics group and in nine (21.4% patients in the control group (p=0.002. There were three cases of intraabdominal abscess and four cases of pneumonia in the control group, whereas we observed no infections in patients receiving symbiotics (p=0.001. Conclusion: the perioperative administration of symbiotics significantly reduced postoperative infection rates in patients with colorectal cancer. Additional studies are needed to confirm the role of symbiotics in the surgical treatment of colorectal cancer.

  6. Evaluation of Candida Albicans Biofilm Formation on Various Dental ...

    African Journals Online (AJOL)

    2016-06-24

    Jun 24, 2016 ... This study compared the susceptibility of six dental restorative materials to Candida albicans adhesion. ... found for the composite and the compomer samples. ..... Candida colonization on acrylic resins and denture liners:.

  7. Short peptides allowing preferential detection of Candida albicans hyphae.

    Science.gov (United States)

    Kaba, Hani E J; Pölderl, Antonia; Bilitewski, Ursula

    2015-09-01

    Whereas the detection of pathogens via recognition of surface structures by specific antibodies and various types of antibody mimics is frequently described, the applicability of short linear peptides as sensor molecules or diagnostic tools is less well-known. We selected peptides which were previously reported to bind to recombinant S. cerevisiae cells, expressing members of the C. albicans Agglutinin-Like-Sequence (ALS) cell wall protein family. We slightly modified amino acid sequences to evaluate peptide sequence properties influencing binding to C. albicans cells. Among the selected peptides, decamer peptides with an "AP"-N-terminus were superior to shorter peptides. The new decamer peptide FBP4 stained viable C. albicans cells more efficiently in their mature hyphal form than in their yeast form. Moreover, it allowed distinction of C. albicans from other related Candida spp. and could thus be the basis for the development of a useful tool for the diagnosis of invasive candidiasis.

  8. Candida albicans endophthalmitis in a patient with a non-functioning pituitary adenoma evolving into Cushing׳s disease: A case report

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    Eun Kyoung Lee

    2014-10-01

    Full Text Available A 53-year-old woman presented with complaints of blurred vision in the left eye. She had been treated for recurrent non-functioning pituitary adenoma (NFPA. A vitreous biopsy followed by histopathologic examination showed the presence of Candida albicans. Meanwhile, Cushing׳s disease was diagnosed and gamma knife surgery was performed. Vitrectomy and antifungal treatment improved ocular infection and inflammation. Herein, we describe the first case of C. albicans endophthalmitis in a patient with NFPA evolving into Cushing׳s disease.

  9. The roles of CDR1, CDR2, and MDR1 in kaempferol-induced suppression with fluconazole-resistant Candida albicans.

    Science.gov (United States)

    Shao, Jing; Zhang, MengXiang; Wang, TianMing; Li, Yue; Wang, ChangZhong

    2016-01-01

    Fungal infections caused by fluconazole-resistant Candida albicans are an intractable clinical problem, calling for new efficient antifungal drugs. Kaempferol, an active flavonoid, has been considered a potential candidate against Candida species. This work investigates the resistance reversion of kaempferol in fluconazole-resistant C. albicans and the underlying mechanism. The antifungal activities of fluconazole and/or kaempferol were assessed by a series of standard procedures including broth microdilution method, checkerboard assay and time-kill (T-K) test in nine clinical strains as well as a standard reference isolate of C. albicans. Subsequently, the morphological changes, the efflux of rhodamine 6G, and the expressions of CDR 1, CDR 2, and MDR 1 were analysed by scanning electron microscope (SEM), inverted fluorescence microscope and quantitative reverse transcription polymerase chain reaction (qRT-PCR) in C. albicans z2003. For all the tested C. albicans strains, the minimum inhibitory concentrations (MICs) of fluconazole and kaempferol ranged 0.25-32 and 128-256 μg/mL with a range of fractional inhibitory concentration index of 0.257-0.531. In C. albicans z2003, the expression of both CDR 1 and CDR 2 were decreased after exposure to kaempferol alone with negligible rhodamine 6G accumulation, while the expression of CDR 1, CDR 2 and MDR 1 were all decreased when fluconazole and kaempferol were used concomitantly with notable fluorescence of rhodamine 6G observed. Kaempferol-induced reversion in fluconazole-resistant C. albicans might be likely due to the suppression of the expression of CDR1, CDR2 and MDR1.

  10. Frequency and enzymatic activity of Candida albicans isolated from the oral cavity of HIV-positive patients at Fortaleza, Ceará Freqüência e atividade enzimática de Candida albicans isolado da cavidade oral de pacientes HIV-positivos em Fortaleza, Ceará

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    Everardo Albuquerque Menezes

    2006-08-01

    Full Text Available Candida albicans and other species are usually involved in opportunistic infections in patients with acquired immunological deficiency syndrome (AIDS. The virulence mechanisms by which this yeast expresses its pathogenicity include adherence patterns, ability to form pseudomycelia and production of extracellular enzymes, among others. The objective of this research was to verify the frequency of Candida and the production of proteinase and phospholipase in 52 strains of Candida albicans from the oral cavity of patients infected by HIV treated at Hospital São José, AIDS reference and training center in Fortaleza, Ceará. Samples were collected of patients, with or without oral lesions characteristic of candidosis. From 100 patients, 80% presented positivity for Candida: 65% (52 were identified as C. albicans, 27.5% (22 as C. tropicalis, 2.5% (2 as C. glabrata, 2.5% (2 as C. krusei and 2.5% (2 as C. guilliermondii. Among the strains of C. albicans isolated from the oral cavity, proteinase and phospholipase were detected in 69.2% and 73%, respectively. The results suggested that C. albicans was the most frequent species observed, with intermediate expression of proteinase and phospholipase.Candida albicans e outras espécies são usualmente envolvidas em infecções de pacientes com a síndrome da imunodeficiência adquirida (AIDS. Os mecanismos de virulência pelos quais a levedura expressa sua patogenicidade incluem padrões de aderência, habilidade por formar pseudomicélio, produção de enzimas extracelulares e outros. O objetivo deste trabalho foi verificar a freqüência de Candida e a produção de proteinase e fosfolipase em 52 cepas de Candida albicans da cavidade oral de pacientes infectados pelo HIV atendidos no Hospital São José, hospital de referência e centro de treinamento em AIDS em Fortaleza, Ceará. Neste trabalho foram coletadas amostras de pacientes com ou sem lesões características de candidose. Dos cem pacientes 80

  11. Effect of the Ethyl Acetate Fraction of Eugenia uniflora on Proteins Global Expression during Morphogenesis in Candida albicans

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    Walicyranison P. Silva-Rocha

    2017-09-01

    Full Text Available Candida albicans is able to switch from yeast to hyphal growth and this is an essential step for tissue invasion and establishment of infection. Due to the limited drug arsenal used to treat fungal infections and the constant emergence of resistant strains, it is important to search for new therapeutic candidates. Therefore, this study aimed to investigate by proteomic analysis the role of a natural product (Eugenia uniflora in impairing hypha formation in C. albicans. We also tested the potential action of E. uniflora to prevent and treat oral candidiasis induced in a murine model of oral infection and the ability of polymorphonuclear neutrophils to phagocytize C. albicans cells treated with the ethyl acetate fraction of the extract. We found that this fraction greatly reduced hypha formation after morphogenesis induction in the presence of serum. Besides, several proteins were differentially expressed in cells treated with the fraction. Surprisingly, the ethyl acetate fraction significantly reduced phagocytosis in C. albicans (Mean 120.36 ± 36.71 yeasts/100 PMNs vs. 44.68 ± 19.84 yeasts/100 PMNs. Oral candidiasis was attenuated when C. albicans cells were either pre-incubated in the presence of E. uniflora or when the fraction was applied to the surface of the oral cavity after infection. These results were consistent with the reduction in CFU counts (2.36 vs. 1.85 Log10 CFU/ml and attenuation of tissue damage observed with histopathological analysis of animals belonging to treated group. We also observed shorter true hyphae by direct examination and histopathological analysis, when cells were treated with the referred natural product. The E. uniflora ethyl acetate fraction was non-toxic to human cells. E. uniflora may act on essential proteins mainly related to cellular structure, reducing the capacity of filamentation and attenuating infection in a murine model, without causing any toxic effect on human cells, suggesting that it may be a

  12. Dental Caries in Rats Associated with Candida albicans

    OpenAIRE

    Klinke, Thomas; Guggenheim, Bernhard; Klimm, Wolfgang; Thurnheer, Thomas

    2014-01-01

    In addition to occasional opportunistic colonization of the oral mucosa, Candida albicans is frequently found in carious dentin. The yeast’s potential to induce dental caries as a consequence of its pronounced ability to produce and tolerate acids was investigated. Eighty caries-active Osborne-Mendel rats were raised on an ampicillin-supplemented diet and exposed to C. albicans and/or Streptococcus mutans, except for controls. Throughout the 28-day test period, the animals were offered the mo...

  13. Aktivitas Antijamur Senyawa Bioaktif Ekstrak Gelidium Latifolium Terhadap Candida Albicans

    OpenAIRE

    Lutfiyanti, Rosiska; Ma'ruf, Widodo Farid; Dewi, Eko Nurcahya

    2012-01-01

    Gelidium sp. has bioactive compounds which is estimated has potential activity as antifungal. The aim of this study were to know bioactive compounds from Gelidium latifolium with different solvent, to know the potency of Gelidium latifolium extract as antifungal towards C. albicans and to know the effect of different concentration of Gelidium latifolium extract towards antifungal activity. The result showed that the methanol extract is able to produce inhibition zones toward Candida albicans,...

  14. Allergen cross-reactivity between Pityrosporum orbiculare and Candida albicans.

    Science.gov (United States)

    Huang, X; Johansson, S G; Zargari, A; Nordvall, S L

    1995-08-01

    Pityrosporum orbiculare and Candida albicans extracts were separated by SDS-PAGE, and IgE binding was detected by immunoblotting with 21 patient sera that were RAST positive to both yeasts. Cross-wise inhibition was performed of IgE binding of a serum pool containing IgE antibodies to both yeasts. The pool was mixed with serial dilutions of P. orbiculare or C. albicans extracts, and incubated with strips containing separated allergen. IgE binding was quantified by densitometric scanning and percent inhibition was calculated as well as the respective ratios between required extract concentration for 50% inhibition in heterologous compared to homologous inhibition for each component (inhibition ratio). Ten components of P. orbiculare were detected by more than 60% of the sera. IgE binding to C. albicans was weak, and only to four bands was IgE binding detected by more than 30% of the sera. The most important C. albicans allergen was a 48-kDa band, to which IgE of half of the patient sera bound. There was little inhibition of IgE binding to P. orbiculare with C. albicans. Thus, all but three components exhibited an inhibition ratio higher than 100. The inhibition ratio of the 48-kDa C. albicans compound was 50, thus indicating some degree of cross-reactivity. Significant cross-reactivity was shown by C. albicans compounds of 18, 24, 26, 34, and 38 kDa, the inhibition ratios of which were less than 10. There was some degree of cross-reactivity between apparent protein allergens of the two yeasts, but IgE antibodies to C. albicans do not merely reflect sensitization to P. orbiculare.

  15. In vitro susceptibility of Candida albicans clinical isolates to eight antifungal agents in Ouagadougou (Burkina Faso).

    Science.gov (United States)

    Zida, A; Yacouba, A; Bamba, S; Sangare, I; Sawadogo, M; Guiguemde, T; Kone, S; Traore, L K; Ouedraogo-Traore, R; Guiguemde, R T

    2017-12-01

    In recent years, the infection Candida albicans infection worldwide has risen, and the incidence of resistance to traditional antifungal therapies is also increasing. The aim of this study was to evaluate in vitro susceptibility of C. albicans clinical isolates to eight antifungal agents in Ouagadougou. A cross-sectional study was conducted from January 2013 to December 2015 at Yalgado Ouédraogo University Teaching Hospital. Two hundred seven strains have been isolated from 347 symptomatic patients received in different clinical services. Samples were cultured on Sabouraud Dextrose Agar supplemented with Cloramphenicol. Isolates were diagnosed as C. albicans using germ tube test, chlamydospore formation on Corn Meal Agar, and Api-Candida test (Biomérieux). Antifungal susceptibility testing was performed by disk diffusion method and isolates classified as susceptible, susceptible dose-dependent and resistant. Three hundred forty-seven (347) patients are included in this study. Two hundred and six (206) out of 347 collected samples (59.36%) were found positive for C. albicans. The strains were mostly isolated from vulvovaginal (49%) and oral infections (40.3%). The highest resistance rates of azoles were obtained with fluconazole (66.5%), itraconazole (52.3%) and ketoconazole (22.9%) when all clinical isolates were included. The resistance rates of fluconazole, itraconazole and ketoconazole remain highest for vulvovaginal and oral isolates. The rate of resistance to the polyene amphotericin B was 32.0% for all clinical isolates and was 56.4% for vulvovaginal strains. Resistance rate to nystatin was 6.3% for all clinical isolates. Cross-resistance analysis with data of all clinical strains revealed that the incidence of resistance to ketoconazole and itraconazole in fluconazole-resistant isolates was significantly higher than recorded for fluconazole-susceptible isolates. In vitro C. albicans antifungal susceptibility test in this study showed relatively high

  16. In Vitro Activities of Terbinafine against Cutaneous Isolates of Candida albicans and Other Pathogenic Yeasts

    Science.gov (United States)

    Ryder, Neil S.; Wagner, Sonja; Leitner, Ingrid

    1998-01-01

    Terbinafine is active in vitro against a wide range of pathogenic fungi, including dermatophytes, molds, dimorphic fungi, and some yeasts, but earlier studies indicated that the drug had little activity against Candida albicans. In contrast, clinical studies have shown topical and oral terbinafine to be active in cutaneous candidiasis and Candida nail infections. In order to define the anti-Candida activity of terbinafine, we tested the drug against 350 fresh clinical isolates and additional strains by using a broth dilution assay standardized according to the guidelines of the National Committee for Clinical Laboratory Standards (NCCLS) M27-A assay. Terbinafine was found to have an MIC of 1 μg/ml for reference C. albicans strains. For 259 clinical isolates, the MIC at which 50% of the isolates are inhibited (MIC50) of terbinafine was 1 μg/ml (fluconazole, 0.5 μg/ml), and the MIC90 was 4 μg/ml (fluconazole, 1 μg/ml). Terbinafine was highly active against Candida parapsilosis (MIC90, 0.125 μg/ml) and showed potentially interesting activity against isolates of Candida dubliniensis, Candida guilliermondii, Candida humicola, and Candida lusitaniae. It was not active against the Candida glabrata, Candida krusei, and Candida tropicalis isolates in this assay. Cryptococcus laurentii and Cryptococcus neoformans were highly susceptible to terbinafine, with MICs of 0.06 to 0.25 μg/ml. The NCCLS macrodilution assay provides reproducible in vitro data for terbinafine against Candida and other yeasts. The MICs for C. albicans and C. parapsilosis are compatible with the known clinical efficacy of terbinafine in cutaneous infections, while the clinical relevance of its activities against the other species has yet to be determined. PMID:9593126

  17. Effects on muscle performance of NSAID treatment with piroxicam versus placebo in geriatric patients with acute infection-induced inflammation. A double blind randomized controlled trial.

    Science.gov (United States)

    Beyer, Ingo; Bautmans, Ivan; Njemini, Rose; Demanet, Christian; Bergmann, Pierre; Mets, Tony

    2011-12-30

    Inflammation is the main cause of disease-associated muscle wasting. In a previous single blind study we have demonstrated improved recovery of muscle endurance following celecoxib treatment in hospitalized geriatric patients with acute infection. Here we further evaluate NSAID treatment with piroxicam in a double blind RCT and investigate the role of cytokines and heat shock proteins (Hsp) with respect to muscle performance. We hypothesized that NSAID treatment would preserve muscle performance better than antibiotic treatment alone, by reducing infection-associated inflammation and by increasing expression of cytoprotective Hsp. Consecutive admissions to the geriatric ward were screened. 30 Caucasian patients, median age 84.5 years, with acute infection-induced inflammation and serum levels of CRP > 10 mg/L were included and randomized to active treatment with 10 mg piroxicam daily or placebo. Assessment comprised general clinical and biochemical parameters, 25 cytokines in serum, intra-and extracellular Hsp27 and Hsp70, Elderly Mobility Scale (EMS) scores, grip strength (GS), fatigue resistance (FR) and lean body mass (LBM). Patients were evaluated until discharge with a maximum of 3 weeks after treatment allocation. EMS scores, FR and grip work (GW), a measure taking into account GS and FR, significantly improved with piroxicam, but not with placebo. Early decreases in IL-6 serum levels with piroxicam correlated with better muscle performance at week 2. Basal expression of Hsp27 in monocytes without heat challenge (WHC) was positively correlated with FR at baseline and significantly increased by treatment with piroxicam compared to placebo. Profound modifications in the relationships between cytokines or Hsp and changes in muscle parameters were observed in the piroxicam group. Piroxicam improves clinically relevant measures of muscle performance and mobility in geriatric patients hospitalized with acute infection-induced inflammation. Underlying mechanisms may

  18. Development of Anti-Virulence Approaches for Candidiasis via a Novel Series of Small-Molecule Inhibitors of Candida albicans Filamentation

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    Jesus A. Romo

    2017-12-01

    Full Text Available Candida albicans remains the main etiologic agent of candidiasis, the most common fungal infection and now the third most frequent infection in U.S. hospitals. The scarcity of antifungal agents and their limited efficacy contribute to the unacceptably high morbidity and mortality rates associated with these infections. The yeast-to-hypha transition represents the main virulence factor associated with the pathogenesis of C. albicans infections. In addition, filamentation is pivotal for robust biofilm development, which represents another major virulence factor for candidiasis and further complicates treatment. Targeting pathogenic mechanisms rather than growth represents an attractive yet clinically unexploited approach in the development of novel antifungal agents. Here, we performed large-scale phenotypic screening assays with 30,000 drug-like small-molecule compounds within ChemBridge’s DIVERSet chemical library in order to identify small-molecule inhibitors of C. albicans filamentation, and our efforts led to the identification of a novel series of bioactive compounds with a common biaryl amide core structure. The leading compound of this series, N-[3-(allyloxy-phenyl]-4-methoxybenzamide, was able to prevent filamentation under all liquid and solid medium conditions tested, suggesting that it impacts a common core component of the cellular machinery that mediates hypha formation under different environmental conditions. In addition to filamentation, this compound also inhibited C. albicans biofilm formation. This leading compound also demonstrated in vivo activity in clinically relevant murine models of invasive and oral candidiasis. Overall, our results indicate that compounds within this series represent promising candidates for the development of novel anti-virulence approaches to combat C. albicans infections.

  19. Candida albicans survival and biofilm formation under starvation conditions.

    Science.gov (United States)

    Ning, Y; Hu, X; Ling, J; Du, Y; Liu, J; Liu, H; Peng, Z

    2013-01-01

    To investigate the survival and biofilm formation capacity of Candida albicans in starvation and under anaerobic conditions. Candida albicans growth and survival were monitored in vitro for up to 8 months. Fungal suspensions from late exponential, stationary and starvation phases were incubated on human dentine, polystyrene and glass slides. Scanning electron microscopy (SEM) was used to observe the process of biofilm formation. 2,3-bis(2-Methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxyanilide inner salt (XTT) reduction assay was performed to quantify the biofilm formation capability, and confocal laser scanning microscopy (CLSM) was used to study and make semi-quantitative comparisons of the ultrastructure of biofilms formed on human dentine. 'XTT bioactivity' and 'COMSTAT results' were analysed by two-way analysis of variance (ANOVA) and one-way ANOVA, respectively. Candida albicans survived for over six months. SEM demonstrated that starving C. albicans produced mature biofilms on different substrata. C. albicans of the same growth phase incubated on human dentine displayed significantly higher biofilm formation capability than on polystyrene or glass slides (P roughness coefficient and surface/volume ratio (P < 0.05). Candida albicans cells can survive and form biofilms in anaerobic and nutrient-limited conditions and may pose a treatment challenge. © 2012 International Endodontic Journal.

  20. Frequency of Candida albicans in Patients with Funguria.

    Science.gov (United States)

    Jamil, Sana; Jamil, Naz; Saad, Uzma; Hafiz, Saleem; Siddiqui, Sualleha

    2016-02-01

    To determine the frequency of Candida albicansin patients with funguria. Descriptive cross-sectional study. Department of Microbiology, Sindh Institute of Urology and Transplantation, from July to December 2012. Patients’ urine samples with fungus/Candida were included. Candida albicans was identified by the production of tubular structures (germ tubes) on microscopy as per standard procedure followed by inoculation on Chrom agar (Oxoid) and Corn Meal-Tween 80 agar (Oxoid). The identification of other non-albicans Candidaspecies was also done both microscopically and macroscopically as per standard procedure. Out of the 289 isolates, 204 (70.6%) were male patients and 85 (29.4%) were female patients, with 165 (57.1%) from the out-patients and 124 (42.9%) from the in-patients. Five species of Candidawere found to be prevalent including 87 (30.1%) Candida albicans, 176 (60.9%) Candida tropicalis, 14 (4.8%) Candida parapsilosis, 8 (2.8%) Candida glabrata and 4 (1.4%) Candida lusitaniae. Majority of patients with funguria were aged above 50 years (60.2%). In the present study, 30.1% patients with funguria had Candida albicans. The most frequently isolated species was Candida tropicalis(60.9%), followed by other non-albicansCandida. This study has shown the emergence of non-albicans Candidaas a major cause of candiduria.

  1. Contribution of Fdh3 and Glr1 to Glutathione Redox State, Stress Adaptation and Virulence in Candida albicans.

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    Anna T Tillmann

    Full Text Available The major fungal pathogen of humans, Candida albicans, is exposed to reactive nitrogen and oxygen species following phagocytosis by host immune cells. In response to these toxins, this fungus activates potent anti-stress responses that include scavenging of reactive nitrosative and oxidative species via the glutathione system. Here we examine the differential roles of two glutathione recycling enzymes in redox homeostasis, stress adaptation and virulence in C. albicans: glutathione reductase (Glr1 and the S-nitrosoglutathione reductase (GSNOR, Fdh3. We show that the NADPH-dependent Glr1 recycles GSSG to GSH, is induced in response to oxidative stress and is required for resistance to macrophage killing. GLR1 deletion increases the sensitivity of C. albicans cells to H2O2, but not to formaldehyde or NO. In contrast, Fdh3 detoxifies GSNO to GSSG and NH3, and FDH3 inactivation delays NO adaptation and increases NO sensitivity. C. albicans fdh3⎔ cells are also sensitive to formaldehyde, suggesting that Fdh3 also contributes to formaldehyde detoxification. FDH3 is induced in response to nitrosative, oxidative and formaldehyde stress, and fdh3Δ cells are more sensitive to killing by macrophages. Both Glr1 and Fdh3 contribute to virulence in the Galleria mellonella and mouse models of systemic infection. We conclude that Glr1 and Fdh3 play differential roles during the adaptation of C. albicans cells to oxidative, nitrosative and formaldehyde stress, and hence during the colonisation of the host. Our findings emphasise the importance of the glutathione system and the maintenance of intracellular redox homeostasis in this major pathogen.

  2. The Effect of Aqueous and Ethanolic Extracts of Teucrium polium on Candida Albicans and Two Species of Malassezia

    Directory of Open Access Journals (Sweden)

    Maryam Nadimi

    2013-08-01

    Full Text Available Background: Teucrium polium L. is a medicinal plant, which due to its antimicrobial, antispasmodic and anti-tumor properties has been used in traditional medicine for over 2000 years. The aim of this research was to study the effect of aqueous and ethanolic extracts of Teucrium polium L. against three strains of Candida albicans (ATCC 62061, ATCC 1677, and NCPF 3153, Malassezia furfur and Malassezia globosa using pour plate method. Materials and Methods: Teucrium polium L. was collected from Broojen area during the spring. The plant was dried and powdered. The aqueous and ethanolic extracts were prepared from the fine powder. Different concentrations of extracts (1, 2, 4, and 8 mg/ml were made in Sabouraud Dextrose Agar (SDA and modified Leeming-Notman Agar (MLNA medium for Candida albicans, Malassezia furfur and Malassezia globosa. 1.5×106 cfu/ml of yeasts, were cultured on media and incubated at 37ºC and 32ºC respectively. Pour plate method was used to assess the antifungal activity of these extracts.Results: The inhibitory effect of ethanolic extract of Teucrium polium L. on the three strains of Candida albicans was depended on concentration level of extracts in media. Aqueous extract had inhibitory effect on Candida albicans (NCPF 3153 only, and with increasing of the extract concentration, the number of colonies was decreased, so that in concentration of 8 mg/ml, no growth was seen. Aqueous and ethanolic extracts had no inhibitory effect on Malassezia species. Conclusion: Teucrium polium L. extracts have considerable inhibitory effect on different strains of Candida albicans. Further investigations are needed to detect the effectiveness of this plant in treatment of Candida infections.

  3. Isolation and Characterization of a Double Stranded DNA Megavirus Infecting the Toxin-Producing Haptophyte Prymnesium parvum

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    Ben A. Wagstaff

    2017-03-01

    Full Text Available Prymnesium parvum is a toxin-producing haptophyte that causes harmful algal blooms globally, leading to large-scale fish kills that have severe ecological and economic implications. For the model haptophyte, Emiliania huxleyi, it has been shown that large dsDNA viruses play an important role in regulating blooms and therefore biogeochemical cycling, but much less work has been done looking at viruses that infect P. parvum, or the role that these viruses may play in regulating harmful algal blooms. In this study, we report the isolation and characterization of a lytic nucleo-cytoplasmic large DNA virus (NCLDV collected from the site of a harmful P. parvum bloom. In subsequent experiments, this virus was shown to infect cultures of Prymnesium sp. and showed phylogenetic similarity to the extended Megaviridae family of algal viruses.

  4. Silver nanoparticles embedded mesoporous SiO_2 nanosphere: an effective anticandidal agent against Candida albicans 077

    International Nuclear Information System (INIS)

    Qasim, M; Paik, P; Das, D; Singh, Braj R; Naqvi, A H

    2015-01-01

    Candida albicans is a diploid fungus that causes common infections such as denture stomatitis, thrush, urinary tract infections, etc. Immunocompromised patients can become severely infected by this fungus. Development of an effective anticandidal agent against this pathogenic fungus, therefore, will be very useful for practical application. In this work, Ag-embedded mesoporous silica nanoparticles (mSiO_2@AgNPs) have successfully been synthesized and their anticandidal activities against C. albicans have been studied. The mSiO_2@AgNPs nanoparticles (d ∼ 400 nm) were designed using pre-synthesized Ag nanoparticles and tetraethyl orthosilicate (TEOS) as a precursor for SiO_2 in the presence of cetyltrimethyl ammonium bromide (CTAB) as an easily removable soft template. A simple, cost-effective, and environmentally friendly approach has been adopted to synthesize silver (Ag) nanoparticles using silver nitrate and leaf extract of Azadirachta indica. The mesopores, with size-equivalent diameter of the micelles (d = 4–6 nm), were generated on the SiO_2 surface by calcination after removal of the CTAB template. The morphology and surface structure of mSiO_2@AgNPs were characterized through x-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), particle size analysis (PSA), atomic force microscopy (AFM), field emission scanning electron microscopy (FESEM), Brunauer–Emmett–Teller (BET) and high-resolution transmission electron microscopy (HRTEM). The HRTEM micrograph reveals the well-ordered mesoporous structure of the SiO_2 sphere. The antifungal activities of mSiO_2@AgNPs on the C. albicans cell have been studied through microscopy and are seen to increase with increasing dose of mSiO_2@AgNPs, suggesting mSiO_2@AgNPs to be a potential antifungal agent for C. albicans 077. (paper)

  5. Effects of 60 Cobalt ionizing radiation in morphology and metabolism of yeasts and Chlamydospore of Candida albicans

    International Nuclear Information System (INIS)

    Grillo, Michel R.F.; Demicheli, Marina C.; Andrade Junior, Heitor F.; Galiesteo Junior, Andres A.J.

    2015-01-01

    Candida albicans is a fungus responsible for 80-90% of fungal infections, as the symptoms are similar to those of systemic bacterial infections there is a difficulty for immediate diagnosis. These difficulties can lead to delays of antifungal therapy, which contributes to the high mortality rates associated with this infection. Resistance structures referred to as chlamydospores are very common in the pathogen, representing different cell types that form in response to certain genetic or environmental conditions. Recently, various antifungal agents and new therapeutic strategies have come into use, allowing the fungus to acquire a resistance to the drugs. The use of ionizing radiation has been widely employed for the production of immunogens against various parasites. In this work, we evaluate the effects of gamma radiation ( 60 Co) in yeast and chlamydospore of C. albicans with doses ranging from 320 to 10.240 Gy with Cobalt 60. Subsequently the samples were plated and after seven days, the colony forming units (CFU) told. The viability of irradiated cells were evaluated using the Janus green dye. A dose of 6000 Gy was considered ideal for the mitigation of chlamydospore and yeast. The dimorphic change mechanisms of both fungal structures were not harmed. The viability of chlamydospores remained above 70% while the yeast viability remained above 85%. By transmission electron microscopy and fluorescence microscopy may be noted cytoplasmic changes, defects in the cell wall, mitochondria, and the presence of partially preserved vesicles of both morphological forms of C. albicans. Irradiation both chlamydospore as C. albicans yeast allows the suppression of their reproduction, opening the possibility of their use in future candidate immunogens. (author)

  6. Effects of 60 Cobalt ionizing radiation in morphology and metabolism of yeasts and Chlamydospore of Candida albicans

    Energy Technology Data Exchange (ETDEWEB)

    Grillo, Michel R.F.; Demicheli, Marina C.; Andrade Junior, Heitor F.; Galiesteo Junior, Andres A.J., E-mail: galisteo@usp.br [Universidade de Sao Paulo (IMTSP/USP), Sao Paulo, SP (Brazil). Instituto de Medicina Tropical. Lab. de Protozoologia; Takakura, Cleusa F.H. [Universidade de Sao Paulo (FM/USP), Sao Paulo, SP (Brazil). Departamento de Patologia de Molestias Transmissiveis. Lab. de Patologia; Negro, Gilda M.B. del [Universidade de Sao Paulo (HCFM/USP/IMTSP/LIM-53), Sao Paulo, SP (Brazil). Hospital das Clinicas. Lab. de Micologia; Nascimento, Nanci do [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2015-07-01

    Candida albicans is a fungus responsible for 80-90% of fungal infections, as the symptoms are similar to those of systemic bacterial infections there is a difficulty for immediate diagnosis. These difficulties can lead to delays of antifungal therapy, which contributes to the high mortality rates associated with this infection. Resistance structures referred to as chlamydospores are very common in the pathogen, representing different cell types that form in response to certain genetic or environmental conditions. Recently, various antifungal agents and new therapeutic strategies have come into use, allowing the fungus to acquire a resistance to the drugs. The use of ionizing radiation has been widely employed for the production of immunogens against various parasites. In this work, we evaluate the effects of gamma radiation ({sup 60}Co) in yeast and chlamydospore of C. albicans with doses ranging from 320 to 10.240 Gy with Cobalt 60. Subsequently the samples were plated and after seven days, the colony forming units (CFU) told. The viability of irradiated cells were evaluated using the Janus green dye. A dose of 6000 Gy was considered ideal for the mitigation of chlamydospore and yeast. The dimorphic change mechanisms of both fungal structures were not harmed. The viability of chlamydospores remained above 70% while the yeast viability remained above 85%. By transmission electron microscopy and fluorescence microscopy may be noted cytoplasmic changes, defects in the cell wall, mitochondria, and the presence of partially preserved vesicles of both morphological forms of C. albicans. Irradiation both chlamydospore as C. albicans yeast allows the suppression of their reproduction, opening the possibility of their use in future candidate immunogens. (author)

  7. Searching for new strategies against biofilm infections: Colistin-AMP combinations against Pseudomonas aeruginosa and Staphylococcus aureus single- and double-species biofilms.

    Directory of Open Access Journals (Sweden)

    Paula Jorge

    Full Text Available Antimicrobial research is being pressured to look for more effective therapeutics for the ever-growing antibiotic-resistant infections, and antimicrobial peptides (AMP and antimicrobial combinations are promising solutions. This work evaluates colistin-AMP combinations against two major pathogens, Pseudomonas aeruginosa and Staphylococcus aureus, encompassing non- and resistant strains. Colistin (CST combined with the AMP temporin A (TEMP-A, citropin 1.1 (CIT-1.1 and tachyplesin I linear analogue (TP-I-L was tested against planktonic, single- and double-species biofilm cultures. Overall synergy for planktonic P. aeruginosa and synergy/additiveness for planktonic S. aureus were observed. Biofilm growth prevention was achieved with synergy and additiveness. Pre-established 24 h-old biofilms were harder to eradicate, especially for S. aureus and double-species biofilms; still, some synergy and addictiveness was observed for higher concentrations, including for the biofilms of resistant strains. Different treatment times and growth media did not greatly influence AMP activity. CST revealed low toxicity compared with the other AMP but its combinations were toxic for high concentrations. Overall, combinations reduced effective AMP concentrations, mainly in prevention scenarios. Improvement of effectiveness and toxicity of therapeutic strategies will be further investigated.

  8. Effect of Streptococcus salivarius K12 on the in vitro growth of Candida albicans and its protective effect in an oral candidiasis model.

    Science.gov (United States)

    Ishijima, Sanae A; Hayama, Kazumi; Burton, Jeremy P; Reid, Gregor; Okada, Masashi; Matsushita, Yuji; Abe, Shigeru

    2012-04-01

    Oral candidiasis is often accompanied by severe inflammation, resulting in a decline in the quality of life of immunosuppressed individuals and elderly people. To develop a new oral therapeutic option for candidiasis, a nonpathogenic commensal oral probiotic microorganism, Streptococcus salivarius K12, was evaluated for its ability to modulate Candida albicans growth in vitro, and its therapeutic activity in an experimental oral candidiasis model was tested. In vitro inhibition of mycelial growth of C. albicans was determined by plate assay and fluorescence microscopy. Addition of S. salivarius K12 to modified RPMI 1640 culture medium inhibited the adherence of C. albicans to the plastic petri dish in a dose-dependent manner. Preculture of S. salivarius K12 potentiated its inhibitory activity for adherence of C. albicans. Interestingly, S. salivarius K12 was not directly fungicidal but appeared to inhibit Candida adhesion to the substratum by preferentially binding to hyphae rather than yeast. To determine the potentially anti-infective attributes of S. salivarius K12 in oral candidiasis, the probiotic was administered to mice with orally induced candidiasis. Oral treatment with S. salivarius K12 significantly protected the mice from severe candidiasis. These findings suggest that S. salivarius K12 may inhibit the process of invasion of C. albicans into mucous surfaces or its adhesion to denture acrylic resins by mechanisms not associated with the antimicrobial activity of the bacteriocin. S. salivarius K12 may be useful as a probiotic as a protective tool for oral care, especially with regard to candidiasis.

  9. A novel role of the ferric reductase Cfl1 in cell wall integrity, mitochondrial function, and invasion to host cells in Candida albicans.

    Science.gov (United States)

    Yu, Qilin; Dong, Yijie; Xu, Ning; Qian, Kefan; Chen, Yulu; Zhang, Biao; Xing, Laijun; Li, Mingchun

    2014-11-01

    Candida albicans is an important opportunistic pathogen, causing both superficial mucosal infections and life-threatening systemic diseases. Iron acquisition is an important factor for pathogen-host interaction and also a significant element for the pathogenicity of this organism. Ferric reductases, which convert ferric iron into ferrous iron, are important components of the high-affinity iron uptake system. Sequence analyses have identified at least 17 putative ferric reductase genes in C. albicans genome. CFL1 was the first ferric reductase identified in C. albicans. However, little is known about its roles in C. albicans physiology and pathogenicity. In this study, we found that disruption of CFL1 led to hypersensitivity to chemical and physical cell wall stresses, activation of the cell wall integrity (CWI) pathway, abnormal cell wall composition, and enhanced secretion, indicating a defect in CWI in this mutant. Moreover, this mutant showed abnormal mitochondrial activity and morphology, suggesting a link between ferric reductases and mitochondrial function. In addition, this mutant displayed decreased ability of adhesion to both the polystyrene microplates and buccal epithelial cells and invasion of host epithelial cells. These findings revealed a novel role of C. albicans Cfl1 in maintenance of CWI, mitochondrial function, and interaction between this pathogen and the host. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  10. Infection,

    Science.gov (United States)

    1980-10-16

    characteristic in severe gram-negative sepsis. Hypertriglyceridemia results from an increase in hepatic synthesis in combination with diminished activity of...induced stress, and tissue repair (1). The magnitude and type of nutritional losses caused by an infection reflect both the severity and duration of an... several functional forms of nutrient loss must be anticipated. Functional losses are defined as the within-body losses of nutrients due to infection

  11. [Sensitivity to disinfectants of Candid albicans strains isolated from the hospital environment].

    Science.gov (United States)

    Tadeusiak, B

    1998-01-01

    In recent years an increase of the incidence of Candida infections caused mainly by C. albicans strains especially in high risk inpatients with neoplasms, decreased immunity, burns and after treatment with multiple antibiotics has been observed. Candida organisms are particularly dangerous for newborns being responsible for about 30% of septicaemia cases in newborns in intensive care units. Fungal infections can be endogenous in origin but exogenous infection sources occur in hospitals. The cause of the latter are errors in aseptic management and insufficiently disinfected medical instruments and equipment. The purpose of the study was a comparison of the sensitivity to disinfectants of C. albicans belonging to two laboratory strains C. albicans PZH and C. albicans ATCC 10231 used for the determination of concentrations of two disinfectants used. Besides that, this sensitivity was determined in 14 strains isolated from the patients and one from the circuit of dialysis solution supply to artificial kidney. The study was carried out by the qualitative suspension method, in which the cells in the fluid were subjected to the action of disinfectants, and by the carrier method in which the cells of the microorganisms were present on the surface of metal cylinders. By the suspension method the sensitivity was determined to chloramine T in concentrations from 5.0% to 0.001%, formalin from 10.0% to 0.25%, glutaraldehyde from 2.0% to 0.1%, Septyl from 3.5% to 0.25%. The exposure time was 5, 10, 15, 30 and 60 minutes. The tested strains differed in their sensitivity to the disinfectants used. The greatest interstrain differences were observed in the sensitivity to the disinfectants used. The greatest interstrain differences were observed in the sensitivity to chloramine T. The highest concentrations were tolerated by the strains isolated from the patients and from the artificial kidney circuit as well as by the standard strain ATCC 10231. In the 10-minute exposure time

  12. Combination of CuO nanoparticles and fluconazole: preparation, characterization, and antifungal activity against Candida albicans

    Energy Technology Data Exchange (ETDEWEB)

    Weitz, Iris S., E-mail: irisweitz@braude.ac.il; Maoz, Michal; Panitz, Daniel [ORT Braude College, Department of Biotechnology Engineering (Israel); Eichler, Sigal; Segal, Ester [Technion – Israel Institute of Technology, Department of Biotechnology and Food Engineering (Israel)

    2015-08-15

    Combination therapy becomes an important strategy in the management of invasive fungal infections and emergence of resistant fungi mutants. In this work, we examine the combination of copper oxide (CuO) nanoparticles (NPs) with fluconazole as potential treatment against the pathogenic fungi, Candidaalbicans. CuO NPs (∼7 nm in size) were synthesized with acetate ligands assembled on their surface, as shown by both thermal gravimetric analysis and FTIR spectroscopy. Unlike the commercial CuO (both bulk and 50 nm particles), that are poorly dispersed in water, the interaction with water allows the fine dispersion of the coated CuO NPs and their excellent colloidal stability. The addition of fluconazole to the aqueous CuO dispersion induced spontaneous self-assembly of the NPs into linear pearl-like chains network, shown by cryogenic transmission electron microscopy (cryo-TEM). The antifungal activity of the CuO NPs and their combination with fluconazole (fluconazole–CuO NPs) was studied against C. albicans. The best MIC values were obtained at concentrations as low as 0.2 and 0.3 mg/mL, respectively. The results suggest that fluconazole–CuO NPs can provide a potential alternative treatment for C. albicans infections.

  13. Aberrant lipogenesis is a metabolic marker for azole-resistant candida albicans (Conference Presentation)

    Science.gov (United States)

    Karanja, Caroline; Hong, Weili; Younis, Waleed; Cheng, Ji-Xin; Seleem, Mohamed

    2017-02-01

    Candida is the single most important cause of fungal bloodstream infections worldwide causing significant mortality as high as 50%. This high mortality rate is, in part, due to the inability to rapidly diagnose and simultaneously initiate an effective antifungal therapy early in the disease process. Current culture-based diagnostics are often slow, requiring several days to complete, and are only 50% sensitive in diagnosing candidemia (Candida bloodstream infection). For every 12 hours of delay in starting correct antifungal therapy, the risk of death for a given patient with candidemia increases by 200%. To address this unmet need, we explored the potential of employing stimulated Raman Scattering (SRS) imaging to diagnose candidemia and probe metabolic differences between resistant and susceptible strain at a single cell level. Metabolism is integral to pathogenicity; microorganism have very short life cycles, and therefore only a few hours are needed to observe a full metabolic cycle. SRS imaging at C-H vibration frequency at 2850 cm-1 revealed a substantial difference in lipogenesis between the susceptible and resistant C. albicans. Treating the C. albicans with fluconazole, an antimicrobial drug that targets ergosterol biosynthesis only affected the lipogenesis in the susceptible strain. Our results show that single-cell metabolic imaging under a SRS microscope can be used for diagnose candidemia and early detection of antimicrobial susceptibility.

  14. Possible mechanisms of the antifungal activity of fluconazole in combination with terbinafine against Candida albicans.

    Science.gov (United States)

    Khodavandi, Alireza; Alizadeh, Fahimeh; Vanda, Nasim Aghai; Karimi, Golgis; Chong, Pei Pei

    2014-12-01

    Candidiasis is a term describing infections by yeasts from the genus Candida, the majority Candida albicans. Treatment of such infections often requires antifungals such as the azoles, but increased use of these drugs has led to selection of yeasts with increased resistance to these drugs. Combination therapy would be one of the best strategies for the treatment of candidiasis due to increased resistance to azoles. The antifungal activities of fluconazole and terbinafine were evaluated in vitro alone and in combination using broth microdilution test and time kill study. Eventually the expression level of selected genes involved in ergosterol biosynthesis of Candida was evaluated using semi-quantitative RT-PCR. The obtained results showed the significant MICs ranging from 0.25 to 8 µg/mL followed by FICs ranged from 0.37 to 1 in combination with fluconazole/terbinafine. Our findings have demonstrated that the combination of fluconazole and terbinafine could also significantly reduce the expression of ERG1, 3, and 11 in the cell membrane of Candida in all concentrations tested ranging from 1.73- to 6.99-fold. This study was undertaken with the ultimate goal of finding the probable targets of fluconazole/terbinafine in C. albicans by looking at its effects on cell membrane synthesis.

  15. Identification, Typing, Antifungal Resistance Profile, and Biofilm Formation of Candida albicans Isolates from Lebanese Hospital Patients

    Directory of Open Access Journals (Sweden)

    Ibrahim Bitar

    2014-01-01

    Full Text Available As leading opportunistic fungal pathogens identification and subtyping of Candida species are crucial in recognizing outbreaks of infection, recognizing particularly virulent strains, and detecting the emergence of drug resistant strains. In this study our objective was to compare identification of Candida albicans by the hospitals through the use of conventional versus identification based on the ITS (Internal Transcribed Spacer and to assess biofilm forming capabilities, drug resistance patterns and correlate these with MLST typing. ITS typing revealed a 21.2% hospital misidentification rate. Multidrug resistance to three drugs out of four tested was detected within 25% of the isolates raising concerns about the followed treatment regimens. Drug resistant strains as well as biofilm formers were phylogenetically related, with some isolates with significant biofilm forming capabilities being correlated to those that were multidrug resistant. Such isolates were grouped closely together in a neighbor-joining tree generated by MLST typing indicating phylogenetic relatedness, microevolution, or recurrent infection. In conclusion, this pilot study gives much needed insight concerning C. albicans isolates circulating in Lebanese hospitals and is the first study of its kind correlating biofilm formation, antifungal resistance, and evolutionary relatedness.

  16. The novel Candida albicans transporter Dur31 Is a multi-stage pathogenicity factor.

    Directory of Open Access Journals (Sweden)

    François L Mayer

    Full Text Available Candida albicans is the most frequent cause of oral fungal infections. However, the exact pathogenicity mechanisms that this fungus employs are largely unknown and many of the genes expressed during oral infection are uncharacterized. In this study we sought to functionally characterize 12 previously unknown function genes associated with oral candidiasis. We generated homozygous knockout mutants for all 12 genes and analyzed their interaction with human oral epithelium in vitro. Eleven mutants caused significantly less epithelial damage and, of these, deletion of orf19.6656 (DUR31 elicited the strongest reduction in pathogenicity. Interestingly, DUR31 was not only involved in oral epithelial damage, but in multiple stages of candidiasis, including surviving attack by human neutrophils, endothelial damage and virulence in vivo. In silico analysis indicated that DUR31 encodes a sodium/substrate symporter with 13 transmembrane domains and no human homologue. We provide evidence that Dur31 transports histatin 5. This is one of the very first examples of microbial driven import of this highly cytotoxic antimicrobial peptide. Also, in contrast to wild type C. albicans, dur31Δ/Δ was unable to actively increase local environmental pH, suggesting that Dur31 lies in the extracellular alkalinization hyphal auto-induction pathway; and, indeed, DUR31 was required for morphogenesis. In agreement with this observation, dur31Δ/Δ was unable to assimilate the polyamine spermidine.

  17. The Novel Candida albicans Transporter Dur31 Is a Multi-Stage Pathogenicity Factor

    Science.gov (United States)

    Mayer, François L.; Wilson, Duncan; Jacobsen, Ilse D.; Miramón, Pedro; Große, Katharina; Hube, Bernhard

    2012-01-01

    Candida albicans is the most frequent cause of oral fungal infections. However, the exact pathogenicity mechanisms that this fungus employs are largely unknown and many of the genes expressed during oral infection are uncharacterized. In this study we sought to functionally characterize 12 previously unknown function genes associated with oral candidiasis. We generated homozygous knockout mutants for all 12 genes and analyzed their interaction with human oral epithelium in vitro. Eleven mutants caused significantly less epithelial damage and, of these, deletion of orf19.6656 (DUR31) elicited the strongest reduction in pathogenicity. Interestingly, DUR31 was not only involved in oral epithelial damage, but in multiple stages of candidiasis, including surviving attack by human neutrophils, endothelial damage and virulence in vivo. In silico analysis indicated that DUR31 encodes a sodium/substrate symporter with 13 transmembrane domains and no human homologue. We provide evidence that Dur31 transports histatin 5. This is one of the very first examples of microbial driven import of this highly cytotoxic antimicrobial peptide. Also, in contrast to wild type C. albicans, dur31Δ/Δ was unable to actively increase local environmental pH, suggesting that Dur31 lies in the extracellular alkalinization hyphal auto-induction pathway; and, indeed, DUR31 was required for morphogenesis. In agreement with this observation, dur31Δ/Δ was unable to assimilate the polyamine spermidine. PMID:22438810

  18. Probiotics feeding in prevention of urinary tract infection, bacterial sepsis and necrotizing enterocolitis in preterm infants. A prospective double-blind study.

    Science.gov (United States)

    Dani, Carlo; Biadaioli, Roberto; Bertini, Giovanna; Martelli, Elena; Rubaltelli, Firmino F

    2002-08-01

    It has been suggested that probiotics can reduce the overgrowth of pathogens in the bowels of preterm infants and contribute to the reduction of the incidence of nosocomial infections in neonatal intensive care units (NICUs). The purpose of this study was to evaluate the effectiveness of Lactobacillus GG supplementation in reducing the incidence of urinary tract infections (UTIs), bacterial sepsis and necrotizing enterocolitis (NEC) in preterm infants. A double-blind study was conducted in 12 Italian NICUs. Newborn infants with a gestational age probiotics group (n = 295) and the placebo group (n = 290) exhibited similar clinical characteristics. The duration of Lactobacillus GG and placebo supplementation was 47.3 +/- 26.0 and 48.2 +/- 24.3 days, respectively. Although UTIs (3.4 vs. 5.8%) and NEC (1.4 vs. 2.7%) were found less frequently in the probiotic group compared to the control group, these differences were not significant. Bacterial sepsis was more frequent in the probiotics group (4.4%, n = 11) than in the placebo group (3.8%, n = 9), but the difference was not significant. Seven days of Lactobacillus GG supplementation starting with the first feed is not effective in reducing the incidence of UTIs, NEC and sepsis in preterm infants. Further studies are required to confirm our results in lower birthweight populations. Copyright 2002 S. Karger AG, Basel

  19. Simvastatin inhibits Candida albicans biofilm in vitro.

    Science.gov (United States)

    Liu, Geoffrey; Vellucci, Vincent F; Kyc, Stephanie; Hostetter, Margaret K

    2009-12-01

    By inhibiting the conversion of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) to mevalonate, statins impair cholesterol metabolism in humans. We reasoned that statins might similarly interfere with the biosynthesis of ergosterol, the major sterol of the yeast cell membrane. As assessed by spectrophotometric and microscopic analysis, significant inhibition of biofilm production was noted after 16-h incubation with 1, 2.5, and 5 muM simvastatin, concentrations that did not affect growth, adhesion, or hyphal formation by C. albicans in vitro. Higher concentrations (10, 20, and 25 muM simvastatin) inhibited biofilm by >90% but also impaired growth. Addition of exogenous ergosterol (90 muM) overcame the effects of 1 and 2.5 muM simvastatin, suggesting that at least one mechanism of inhibition is interference with ergosterol biosynthesis. Clinical isolates from blood, skin, and mucosal surfaces produced biofilms; biofilms from bloodstream isolates were similarly inhibited by simvastatin. In the absence of fungicidal activity, simvastatin's interruption of a critical step in an essential metabolic pathway, highly conserved from yeast to man, has unexpected effects on biofilm production by a eukaryotic pathogen.

  20. Pathogenic characteristics of Candida albicans isolated from oral cavities of denture wearers and cancer patients wearing oral prostheses.

    Science.gov (United States)

    Mothibe, J V; Patel, M

    2017-09-01

    Candida albicans cause opportunistic infections including oral candidiasis in immunocompromised patients. It has an ability to cause infection due to its virulence factors. This study investigated the pathogenic characteristics of C. albicans isolated from the oral cavities of healthy subjects and two vulnerable groups, denture wearers and cancer patients wearing oral prostheses. Oral rinse samples were collected and cultured for the quantitative and qualitative analysis of Candida. Twenty strains of C. albicans isolated from the healthy individuals and denture wearers and, 14 strains isolated from the cancer patients were selected and their pathogenic characteristics were measured. The results of the study groups were compared using a Scheffe test for pairwise comparison and a chi square test. Denture wearer and cancer patients with prostheses carried significantly higher number (p production were significantly higher in the strains from denture wearers. In addition, high number of isolates from the denture wearers produced phospholipase and proteinase (85% and 80% respectively) compared to the strains from normal subjects (25% and 60% respectively). Only the germ tube formation and adherence ability were significantly higher in the strains from the cancer patients with prostheses (p = 0.05 and p oral cavity and prostheses is important in the prevention of colonization of Candida and the development of oral candidiasis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Identification of antifungal compounds active against Candida albicans using an improved high-throughput Caenorhabditis elegans assay.

    Directory of Open Access Journals (Sweden)

    Ikechukwu Okoli

    2009-09-01

    Full Text Available Candida albicans, the most common human pathogenic fungus, can establish a persistent lethal infection in the intestine of the microscopic nematode Caenorhabditis elegans. The C. elegans-C. albicans infection model was previously adapted to screen for antifungal compounds. Modifications to this screen have been made to facilitate a high-throughput assay including co-inoculation of nematodes with C. albicans and instrumentation allowing precise dispensing of worms into assay wells, eliminating two labor-intensive steps. This high-throughput method was utilized to screen a library of 3,228 compounds represented by 1,948 bioactive compounds and 1,280 small molecules derived via diversity-oriented synthesis. Nineteen compounds were identified that conferred an increase in C. elegans survival, including most known antifungal compounds within the chemical library. In addition to seven clinically used antifungal compounds, twelve compounds were identified which are not primarily used as antifungal agents, including three immunosuppressive drugs. This assay also allowed the assessment of the relative minimal inhibitory concentration, the effective concentration in vivo, and the toxicity of the compound in a single assay.

  2. Frequency of Candida albicans in Patients with Funguria

    International Nuclear Information System (INIS)

    Jamil, S.; Jamil, N.; Hafiz, S.; Siddiqui, S.; Saad, U.

    2016-01-01

    Objective: To determine the frequency of Candida albicans in patients with funguria. Study Design: Descriptive cross-sectional study. Place and Duration of Study: Department of Microbiology, Sindh Institute of Urology and Transplantation, from July to December 2012. Methodology: Patients urine samples with fungus/Candida were included. Candida albicans was identified by the production of tubular structures (germ tubes) on microscopy as per standard procedure followed by inoculation on Chrom agar (Oxoid) and Corn Meal-Tween 80 agar (Oxoid). The identification of other non-albicans Candida species was also done both microscopically and macroscopically as per standard procedure. Results: Out of the 289 isolates, 204 (70.6 percentage) were male patients and 85 (29.4 percentage) were female patients, with 165 (57.1 percentage) from the out-patients and 124 (42.9 percentage) from the in-patients. Five species of Candida were found to be prevalent including 87 (30.1 percentage) Candida albicans, 176 (60.9 percentage) Candida tropicalis, 14 (4.8 percentage) Candida parapsilosis, 8 (2.8 percentage) Candida glabrata and 4 (1.4 percentage) Candida lusitaniae. Majority of patients with funguria were aged above 50 years (60.2 percentage). Conclusion: In the present study, 30.1 percentage patients with funguria had Candida albicans. The most frequently isolated species was Candida tropicalis (60.9 percentage), followed by other non-albicans Candida. This study has shown the emergence of non-albicans Candida as a major cause of candiduria. (author)

  3. Isolation and characterization of Candida albicans morphological mutants derepressed for the formation of filamentous hypha-type structures

    International Nuclear Information System (INIS)

    Gil, C.; Pomes, R.; Nombela, C.

    1990-01-01

    Several Candida albicans morphological mutants were obtained by a procedure based on a combined treatment with nitrous acid plus UV irradiation and a double-enrichment step to increase the proportion of mutants growing as long filamentous structures. Altered cell morphogenesis in these mutants correlated with an altered colonial phenotype. Two of these mutants, C. albicans NEL102 and NEL103, were selected and characterized. Mutant blastoconidia initiated budding but eventually gave rise to filamentous hypha-type formations. These filaments were long and septate, and they branched very regularly at positions near septa. Calcofluor white (which is known to bind chitin-rich areas) stained septa, branching zones, and filament tips very intensely, as observed under the fluorescence microscope. Wild-type hybrids were obtained by fusing protoplasts of strain NEL102 with B14, another morphological mutant previously described as being permanently pseudomycelial, indicating that genetic determinants responsible for the two altered phenotypes are different. The mutants characterized in this work seemed to sequentially express the morphogenic characteristics of C. albicans, from blastoconidia to hyphae, in the absence of any inducer. Further characterization of these strains could be relevant to gain understanding of the genetic control of dimorphism in this species

  4. Effect of Different Disinfectants on Staphylococcus aureus and Candida albicans Transferred to Alginate and Polyvinylsiloxane Impression Materials

    Directory of Open Access Journals (Sweden)

    Fereydoun Parnia

    2009-12-01

    Full Text Available Background and aims. Several products have been marketed for disinfecting impression materials. The present study evaluated the effect of Deconex, Micro 10, Alprocid and Unisepta Plus sprays on Staphylococcus aureus and Candida albicans transferred to alginate and polyvinylsiloxane impression materials. Materials and methods. A total of 180 impressions of a maxillary model (90 alginate and 90 polyvinylsiloxane impressions were taken for the purpose of this in vitro study. Half of the impressions were infected with Staphylococcus aureus and the other half were infected with Candida albicans. Then the microorganisms were cultured and their counts were determined. Subsequently, the impressions were divided into groups of 15 impressions each. Each group was disinfected with Deconex, Micro10, Alprocid and Unisepta Plus according to manufacturers' instructions except for the control group. The culturing procedure was repeated after disinfection and microbial counts were determined again. Data was analyzed by ANOVA and paired-sample t-test. Results. There were statistically significant differences in the means of S. aureus and C. albicans counts before and after the use of disinfectants (P < 0.05. The use of the four disinfectants reduced S. aureus counts to zero in 80% of the cases. There were no statistically significant differences in S. aureus count reductions between the four disinfectants evaluated (P = 0.31. Micro 10 was more effective on alginate; Deconex was more efficient for polyvinylsiloxane and Alprocid had a better efficacy in both impression materials in eliminating C. albicans (P < 0.05. Conclusion. All the disinfectants evaluated have high disinfecting postentials.

  5. Daya hambat xylitol dan nistation terhadap pertumbuhan Candida albicans (in vitro (Inhibition effect of xylitol and nistatin combination on Candida albicans growth (in vitro

    Directory of Open Access Journals (Sweden)

    Sarah Kartimah Djajusman

    2014-09-01

    Full Text Available Background: The growth of Candida albicans can be controlled by using antifungal such as nystatin. These days we found that using antifungal is not enough to control Candida albicans, we also have to control the intake of sugar by using xylitol. Purpose: Purpose of the study was to determine the optimal inhibitory concentration of xylitol-nystatin in the Candida albicans growth. Methods: This was an in-vitro study using an antimicrobial test of serial dilution with xylitol-nystatin and sucrose–nystatin consentration of 1%, 3%, 5%, 7%, 9%, and 10%.Growth inhibition of C. albicans was determined by the inhibition zone of xylitol + nystatin on C. albicans culture media (in vitro Results: The result of study was the inhibitory consentration of xylitol-nystatin to inhibit Candida albicans growth was 3%-10%. Conclusion: The study showed that combination of xylitol and nystation could inhibit the growth of Candida albicans.Latar belakang: Pertumbuhan Candida albicans dapat dikontrol dengan menggunakan antijamur seperti nistatin. Penggunakan antijamur saja tidak cukup untuk mengontrol Candida albicans, namun perlu pula mengontrol asupan gula dengan menggunakan xylitol. Tujuan: Tujuan dari penelitian ini adalah untuk menentukan konsentrasi hambat optimal xylitol-nistatin dalam pertumbuhan Candida albicans. Metode: Penelitian ini merupakan penelitian in vitro menggunakan uji antimikroba pengenceran serial dengan xylitol-nistatin dan nystatin-sukrosa konsentrasi 1%, 3 %, 5 %, 7%, 9%, dan 10%. Daya hambat pertumbuhan C. albicans diukur dari zona hambat xylitol + nistatin pada media kultur C. albicans (in vitro Hasil: Konsentrasi penghambatan xylitol-nistatin untuk menghambat pertumbuhan Candida albicans adalah 3-10%. Simpulan: Hasil penelitian menunjukkan bahwa kombinasi xylitol dan nystation bisa menghambat pertumbuhan Candida albicans.

  6. Disruption of Specific RNA-RNA Interactions in a Double-Stranded RNA Virus Inhibits Genome Packaging and Virus Infectivity.

    Science.gov (United States)

    Fajardo, Teodoro; Sung, Po-Yu; Roy, Polly

    2015-12-01

    Bluetongue virus (BTV) causes hemorrhagic disease in economically important livestock. The BTV genome is organized into ten discrete double-stranded RNA molecules (S1-S10) which have been suggested to follow a sequential packaging pathway from smallest to largest segment during virus capsid assembly. To substantiate and extend these studies, we have investigated the RNA sorting and packaging mechanisms with a new experimental approach using inhibitory oligonucleotides. Putative packaging signals present in the 3'untranslated regions of BTV segments were targeted by a number of nuclease resistant oligoribonucleotides (ORNs) and their effects on virus replication in cell culture were assessed. ORNs complementary to the 3' UTR of BTV RNAs significantly inhibited virus replication without affecting protein synthesis. Same ORNs were found to inhibit complex formation when added to a novel RNA-RNA interaction assay which measured the formation of supramolecular complexes between and among different RNA segments. ORNs targeting the 3'UTR of BTV segment 10, the smallest RNA segment, were shown to be the most potent and deletions or substitution mutations of the targeted sequences diminished the RNA complexes and abolished the recovery of viable viruses using reverse genetics. Cell-free capsid assembly/RNA packaging assay also confirmed that the inhibitory ORNs could interfere with RNA packaging and further substitution mutations within the putative RNA packaging sequence have identified the recognition sequence concerned. Exchange of 3'UTR between segments have further demonstrated that RNA recognition was segment specific, most likely acting as part of the secondary structure of the entire genomic segment. Our data confirm that genome packaging in this segmented dsRNA virus occurs via the formation of supramolecular complexes formed by the interaction of specific sequences located in the 3' UTRs. Additionally, the inhibition of packaging in-trans with inhibitory ORNs

  7. Nicotine Enhances Interspecies Relationship between Streptococcus mutans and Candida albicans.

    Science.gov (United States)

    Liu, Shiyu; Qiu, Wei; Zhang, Keke; Zhou, Xuedong; Ren, Biao; He, Jinzhi; Xu, Xin; Cheng, Lei; Li, Mingyun

    2017-01-01

    Streptococcus mutans and Candida albicans are common microorganisms in the human oral cavity. The synergistic relationship between these two species has been deeply explored in many studies. In the present study, the effect of alkaloid nicotine on the interspecies between S. mutans and C. albicans is explored. We developed a dual-species biofilm model and studied biofilm biomass, biofilm structure, synthesis of extracellular polysaccharides (EPS), and expression of glucosyltransferases (Gtfs). Biofilm formation and bacterial and fungal cell numbers in dual-species biofilms increased in the presence of nicotine. More C. albicans cells were present in the dual-species biofilms in the nicotine-treated groups as determined by scanning electron microscopy. The synthesis of EPS was increased by 1 mg/ml of nicotine as detected by confocal laser scanning microscopy. The result of qRT-PCR showed gtfs expression was upregulated when 1 mg/ml of nicotine was used. We speculate that nicotine promoted the growth of S. mutans , and more S. mutans cells attracted more C. albicans cells due to the interaction between two species. Since S. mutans and C. albicans are putative pathogens for dental caries, the enhancement of the synergistic relationship by nicotine may contribute to caries development in smokers.

  8. Effects of Antifungal Soaked Silicone Hydrogel Contact Lenses on Candida albicans in an Agar Eye Model.

    Science.gov (United States)

    Phan, Chau-Minh; Bajgrowicz, Magdalena; McCanna, David J; Subbaraman, Lakshman N; Jones, Lyndon

    2016-09-01

    To evaluate the effects of two commercial silicone hydrogel contact lenses (CLs) soaked with natamycin (NA) or fluconazole (FL) on the growth of Candida albicans in an in vitro eye model. Three-D printed molds were used as a cast for making eye-shaped models comprising potato dextrose agar. Senofilcon A (SA) and lotrafilcon B (LB) CLs were incubated with either 2 mL of NA or FL at a concentration of 1 mg/mL for 24 hr. To simulate a fungal infection, the eye models were coated with C. albicans. The drug-soaked lenses were placed on top of the eye models. Seven experimental conditions were examined: (1) NA-SA, (2) NA-LB, (3) FL-SA, (4) FL-LB, (5) SA, (6) LB, and (7) control-no lens. At specified time points (t=1, 8, 16, 24, 48 hr), the agar eyes from each experimental condition were removed from the incubator and photographed. The yeast cells from the 24 and 48 hr time point were also analyzed using light microscopy. At 24 and 48 hr, there was considerable growth observed for all conditions except for the NA-SA and NA-LB conditions. When observed under the microscope at 24 and 48 hr, the morphology of the yeast cells in the FL-SA and SA condition were similar to that of the control (oval shaped). There was limited hyphae growth observed for LB and significant visible hyphae growth for the NA-LB group. For NA-SA, NA-LB, and FL-LB groups, the cells were significantly smaller compared with the control. For NA-SA and NA-LB, there was limited growth of C. albicans observed on the eye models even after 48 hr. Under the microscope, the cell morphology differ noticeably between each testing condition, and is dependent on drug-lens combinations.

  9. Microevolution of Candida albicans in macrophages restores filamentation in a nonfilamentous mutant.

    Directory of Open Access Journals (Sweden)

    Anja Wartenberg

    2014-12-01

    Full Text Available Following antifungal treatment, Candida albicans, and other human pathogenic fungi can undergo microevolution, which leads to the emergence of drug resistance. However, the capacity for microevolutionary adaptation of fungi goes beyond the development of resistance against antifungals. Here we used an experimental microevolution approach to show that one of the central pathogenicity mechanisms of C. albicans, the yeast-to-hyphae transition, can be subject to experimental evolution. The C. albicans cph1Δ/efg1Δ mutant is nonfilamentous, as central signaling pathways linking environmental cues to hyphal formation are disrupted. We subjected this mutant to constant selection pressure in the hostile environment of the macrophage phagosome. In a comparatively short time-frame, the mutant evolved the ability to escape macrophages by filamentation. In addition, the evolved mutant exhibited hyper-virulence in a murine infection model and an altered cell wall composition compared to the cph1Δ/efg1Δ strain. Moreover, the transcriptional regulation of hyphae-associated, and other pathogenicity-related genes became re-responsive to environmental cues in the evolved strain. We went on to identify the causative missense mutation via whole genome- and transcriptome-sequencing: a single nucleotide exchange took place within SSN3 that encodes a component of the Cdk8 module of the Mediator complex, which links transcription factors with the general transcription machinery. This mutation was responsible for the reconnection of the hyphal growth program with environmental signals in the evolved strain and was sufficient to bypass Efg1/Cph1-dependent filamentation. These data demonstrate that even central transcriptional networks can be remodeled very quickly under appropriate selection pressure.

  10. Synthetic arylquinuclidine derivatives exhibit antifungal activity against Candida albicans, Candida tropicalis and Candida parapsilopsis

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    Gilbert Ian

    2011-01-01

    Full Text Available Abstract Background Sterol biosynthesis is an essential pathway for fungal survival, and is the biochemical target of many antifungal agents. The antifungal drugs most widely used to treated fungal infections are compounds that inhibit cytochrome P450-dependent C14α-demethylase (CYP51, but other enzymes of this pathway, such as squalene synthase (SQS which catalyses the first committed step in sterol biosynthesis, could be viable targets. The aim of this study was to evaluate the antifungal activity of SQS inhibitors on Candida albicans, Candida tropicalis and Candida parapsilopsis strains. Methods Ten arylquinuclidines that act as SQS inhibitors were tested as antiproliferative agents against three ATCC strains and 54 clinical isolates of Candida albicans, Candida tropicalis and Candida parapsilopsis. Also, the morphological alterations induced in the yeasts by the experimental compounds were evaluated by fluorescence and transmission electron microscopy. Results The most potent arylquinuclidine derivative (3-[1'-{4'-(benzyloxy-phenyl}]-quinuclidine-2-ene (WSP1267 had a MIC50 of 2 μg/ml for all species tested and MIC90 varying from 4 μg/ml to 8 μg/ml. Ultrathin sections of C. albicans treated with 1 μg/ml of WSP1267 showed several ultrastructural alterations, including (a loss of cell wall integrity, (b detachment of the plasma membrane from the fungal cell wall, (c accumulation of small vesicles in the periplasmic region, (d presence of large electron-dense vacuoles and (e significantly increased cell size and cell wall thickness. In addition, fluorescence microscopy of cells labelled with Nile Red showed an accumulation of lipid droplets in the cytoplasm of treated yeasts. Nuclear staining with DAPI revealed the appearance of uncommon yeast buds without a nucleus or with two nuclei. Conclusion Taken together, our data demonstrate that arylquinuclidine derivatives could be useful as lead compounds for the rational synthesis of new

  11. A randomized, single-ascending-dose, ivermectin-controlled, double-blind study of moxidectin in Onchocerca volvulus infection.

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    Kwablah Awadzi

    2014-06-01

    Full Text Available Control of onchocerciasis as a public health problem in Africa relies on annual mass ivermectin distribution. New tools are needed to achieve elimination of infection. This study determined in a small number of Onchocerca volvulus infected individuals whether moxidectin, a veterinary anthelminthic, is safe enough to administer it in a future large study to further characterize moxidectin's safety and efficacy. Effects on the parasite were also assessed.Men and women from a forest area in South-eastern Ghana without ivermectin mass distribution received a single oral dose of 2 mg (N = 44, 4 mg (N = 45 or 8 mg (N = 38 moxidectin or 150 µg/kg ivermectin (N = 45 with 18 months follow up. All ivermectin and 97%-100% of moxidectin treated participants had Mazzotti reactions. Statistically significantly higher percentages of participants treated with 8 mg moxidectin than participants treated with ivermectin experienced pruritus (87% vs. 56%, rash (63% vs. 42%, increased pulse rate (61% vs. 36% and decreased mean arterial pressure upon 2 minutes standing still after ≥5 minutes supine relative to pre-treatment (61% vs. 27%. These reactions resolved without treatment. In the 8 mg moxidectin and ivermectin arms, the mean±SD number of microfilariae/mg skin were 22.9±21.1 and 21.2±16.4 pre-treatment and 0.0±0.0 and 1.1±4.2 at nadir reached 1 and 3 months after treatment, respectively. At 6 months, values were 0.0±0.0 and 1.6±4.5, at 12 months 0.4±0.9 and 3.4±4.4 and at 18 months 1.8±3.3 and 4.0±4.8, respectively, in the 8 mg moxidectin and ivermectin arm. The reduction from pre-treatment values was significantly higher after 8 mg moxidectin than after ivermectin treatment throughout follow up (p<0.01.The 8 mg dose of moxidectin was safe enough to initiate the large study. Provided its results confirm those from this study, availability of moxidectin to control programmes could help them achieve onchocerciasis elimination

  12. The effect of antiretroviral intensification with dolutegravir on residual virus replication in HIV-infected individuals: a randomised, placebo-controlled, double-blind trial.

    Science.gov (United States)

    Rasmussen, Thomas A; McMahon, James H; Chang, J Judy; Audsley, Jennifer; Rhodes, Ajantha; Tennakoon, Surekha; Dantanarayana, Ashanti; Spelman, Tim; Schmidt, Tina; Kent, Stephen J; Morcilla, Vincent; Palmer, Sarah; Elliott, Julian H; Lewin, Sharon R

    2018-04-06

    Whether ongoing virus replication occurs in HIV-infected individuals on antiretroviral therapy (ART) is unclear; therefore, whether residual virus replication is a barrier to achieving a cure for HIV is also unknown. We aimed to establish whether ART intensification with dolutegravir would reveal or affect residual virus replication in HIV-infected individuals on suppressive treatment. In this randomised, placebo-controlled, double-blind trial, we enrolled HIV-infected adults (aged 18 years and older) receiving combination ART (at least three agents) for at least 3 years from the Alfred Hospital and Melbourne Sexual Health Centre, Melbourne, VIC, Australia. Eligible participants had fewer than 50 copies per mL HIV-1 plasma RNA for more than 3 years and fewer than 20 copies per mL at screening and two CD4 counts higher than 350 cells per μL in the previous 24 months including screening. Participants were randomly assigned (1:1) to receive 50 mg oral dolutegravir or placebo once a day for 56 days in addition to background ART. Follow-up was done at days 1, 3, 7, 14, 28, 56, and 84. The primary outcome was the change from baseline in frequency of 2-long terminal repeat (2-LTR) circles in peripheral blood CD4 cells at day 7. This trial is registered with ClinicalTrials.gov, number NCT02500446. Between Sept 21, 2015, and Sept 19, 2016, 46 individuals were screened for inclusion. 40 were eligible for inclusion and were randomly assigned to the dolutegravir (n=21) or placebo group (n=19). All enrolled participants completed the study procedures and no individuals were lost to follow up. All participants were on suppressive ART with 12% receiving protease inhibitors and the others non-nucleoside reverse transcriptase inhibitors. Median 2-LTR circles fold-change from baseline to day 7 was -0·17 (IQR -0·90 to 0·90) in the dolutegravir group and -0·26 (-1·00 to 1·17) in the placebo group (p=0·17). The addition of dolutegravir to pre-existing ART regimens was safe and

  13. Rutas de glicosilación en Candida albicans: circuitos reguladores y efectos sobre virulencia

    OpenAIRE

    Domínguez Cantero, María del Pilar

    2011-01-01

    [ES]Esta tesis trata sobre las rutas de glicosilación en Candida albicans: circuitos reguladores y efectos sobre virulencia. [EN]This thesis is about glycosylation pathways in Candida albicans: regulatory circuits and effects on virulence.

  14. Non-nematode-derived double-stranded RNAs induce profound phenotypic changes in Meloidogyne incognita and Globodera pallida infective juveniles.

    Science.gov (United States)

    Dalzell, Johnathan J; McMaster, Steven; Johnston, Michael J; Kerr, Rachel; Fleming, Colin C; Maule, Aaron G

    2009-11-01

    Nine non-nematode-derived double-stranded RNAs (dsRNAs), designed for use as controls in RNA interference (RNAi) screens of neuropeptide targets, were found to induce aberrant phenotypes and an unexpected inhibitory effect on motility of root knot nematode Meloidogyne incognita J2s following 24h soaks in 0.1 mg/ml dsRNA; a simple soaking procedure which we have found to elicit profound knockdown of neuronal targets in Globodera pallida J2s. We have established that this inhibitory phenomenon is both time- and concentration-dependent, as shorter 4h soaks in 0.1 mg/ml dsRNA had no negative impact on M. incognita J2 stage worms, yet a 10-fold increase in concentration to 1 mg/ml for the same 4h time period had an even greater qualitative and quantitative impact on worm phenotype and motility. Further, a 10-fold increase of J2s soaked in 0.1 mg/ml dsRNA did not significantly alter the observed phenotypic aberration, which suggests that dsRNA uptake of the soaked J2s is not saturated under these conditions. This phenomenon was not initially observed in potato cyst nematode G. pallida J2s, which displayed no aberrant phenotype, or diminution of migratory activity in response to the same 0.1 mg/ml dsRNA 24h soaks. However, a 10-fold increase in dsRNA to 1mg/ml was found to elicit comparable irregularity of phenotype and inhibition of motility in G. pallida, to that initially observed in M. incognita following a 24h soak in 0.1 mg/ml dsRNA. Again, a 10-fold increase in the number of G. pallida J2s soaked in the same volume of 1 mg/ml dsRNA preparation did not significantly affect the observed phenotypic deviation. We do not observe any global impact on transcript abundance in either M. incognita or G. pallida J2s following 0.1 mg/ml dsRNA soaks, as revealed by reverse transcriptase-PCR and quantitative PCR data. This study aims to raise awareness of a phenomenon which we observe consistently and which we believe signifies a more expansive deficiency in our knowledge and

  15. Elderly nutritional status effection salivary anticandidal capacity against Candida albicans

    Directory of Open Access Journals (Sweden)

    Ria Puspitawati

    2011-06-01

    Full Text Available Background: Elderly often suffer malnutrition and oral candidiasis. Candida albicans (C. albicans which is the most prominent cause of oral candidiasis, is one of commensal oral micro-flora. Nutritional status affect the characteristic of saliva. Saliva is the regulator in the development of C. albicans from comensal into pathogen. Purpose: The purpose of this study was to determining the correlation between elderly nutritional status with salivary total protein and its activity in inhibiting C. albicans growth and biofilm formation. Methods: Using mini nutritional assessment 30 elderly were classified into normal and malnutrition groups. Total protein of unstimulated saliva was measured using Bradford protein assay. The colony forming unit (CFU of C. albicans was counted on 72 hours on SDA cultures without (control or with 2 hour saliva exposure. Biofilm formation was analyzed from the optical density of 10–5 C. albicans suspension without saliva exposure (control or with exposure of 10.000 μg/ml saliva and incubated in 37° C for 2 days. The suspension was put into 96 well plates, stained with crystal-violet dye, and analyzed using microplate reader. Differences between groups were analyzed using independent t-test or Kruskall-Wallis. Correlation between variables was analyzed using Spearman test. Results: Salivary total protein of normal elderly (1.113.5 ± 1.1143.3 was higher than those of malnutrition (613.6 ± 253.6 but not statistically significant (p > 0.05. The CFU of C. albicans exposed to saliva of normal samples (2.060 cfu/ml was significantly lower than control (24.100 cfu/ml and those exposed to malnutrition saliva (5.513.3 cfu/ml. C. albicans biofilm formation is highest in controls (0.177, lower in those exposed to malnourished saliva (0.151 and lowest in those exposed to saliva of good nourished elderly (0.133. Conclusion: Although does not cause significant decrease of salivary total protein, malnutrition in elderly results

  16. Recombinant human growth hormone and rosiglitazone for abdominal fat accumulation in HIV-infected patients with insulin resistance: a randomized, double-blind, placebo-controlled, factorial trial.

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    Marshall J Glesby

    Full Text Available Recombinant human growth hormone (rhGH reduces visceral adipose tissue (VAT volume in HIV-infected patients but can worsen glucose homeostasis and lipoatrophy. We aimed to determine if adding rosiglitazone to rhGH would abrogate the adverse effects of rhGH on insulin sensitivity (SI and subcutaneous adipose tissue (SAT volume.Randomized, double-blind, placebo-controlled, multicenter trial using a 2×2 factorial design in which HIV-infected subjects with abdominal obesity and insulin resistance were randomized to rhGH 3 mg daily, rosiglitazone 4 mg twice daily, combination rhGH + rosiglitazone, or double placebo (control for 12 weeks. The primary endpoint was change in SI by frequently sampled intravenous glucose tolerance test from entry to week 12. Body composition was assessed by whole body magnetic resonance imaging (MRI and dual Xray absorptiometry (DEXA. Seventy-seven subjects were randomized of whom 72 initiated study drugs. Change in SI from entry to week 12 differed across the 4 arms by 1-way ANCOVA (P = 0.02; by pair-wise comparisons, only rhGH (decreasing SI; P = 0.03 differed significantly from control. Changes from entry to week 12 in fasting glucose and glucose area under the curve on 2-hour oral glucose tolerance test differed across arms (1-way ANCOVA P = 0.004, increasing in the rhGH arm relative to control. VAT decreased significantly in the rhGH arms (-17.5% in rhGH/rosiglitazone and -22.7% in rhGH but not in the rosiglitazone alone (-2.5% or control arms (-1.9%. SAT did not change significantly in any arm. DEXA results were consistent with the MRI data. There was no significant rhGH x rosiglitazone interaction for any body composition parameter.The addition of rosiglitazone abrogated the adverse effects of rhGH on insulin sensitivity and glucose tolerance while not significantly modifying the lowering effect of rhGH on VAT.Clinicaltrials.gov NCT00130286.

  17. Recombinant human growth hormone and rosiglitazone for abdominal fat accumulation in HIV-infected patients with insulin resistance: a randomized, double-blind, placebo-controlled, factorial trial.

    Science.gov (United States)

    Glesby, Marshall J; Albu, Jeanine; Chiu, Ya-Lin; Ham, Kirsis; Engelson, Ellen; He, Qing; Muthukrishnan, Varalakshmi; Ginsberg, Henry N; Donovan, Daniel; Ernst, Jerry; Lesser, Martin; Kotler, Donald P

    2013-01-01

    Recombinant human growth hormone (rhGH) reduces visceral adipose tissue (VAT) volume in HIV-infected patients but can worsen glucose homeostasis and lipoatrophy. We aimed to determine if adding rosiglitazone to rhGH would abrogate the adverse effects of rhGH on insulin sensitivity (SI) and subcutaneous adipose tissue (SAT) volume. Randomized, double-blind, placebo-controlled, multicenter trial using a 2×2 factorial design in which HIV-infected subjects with abdominal obesity and insulin resistance were randomized to rhGH 3 mg daily, rosiglitazone 4 mg twice daily, combination rhGH + rosiglitazone, or double placebo (control) for 12 weeks. The primary endpoint was change in SI by frequently sampled intravenous glucose tolerance test from entry to week 12. Body composition was assessed by whole body magnetic resonance imaging (MRI) and dual Xray absorptiometry (DEXA). Seventy-seven subjects were randomized of whom 72 initiated study drugs. Change in SI from entry to week 12 differed across the 4 arms by 1-way ANCOVA (P = 0.02); by pair-wise comparisons, only rhGH (decreasing SI; P = 0.03) differed significantly from control. Changes from entry to week 12 in fasting glucose and glucose area under the curve on 2-hour oral glucose tolerance test differed across arms (1-way ANCOVA P = 0.004), increasing in the rhGH arm relative to control. VAT decreased significantly in the rhGH arms (-17.5% in rhGH/rosiglitazone and -22.7% in rhGH) but not in the rosiglitazone alone (-2.5%) or control arms (-1.9%). SAT did not change significantly in any arm. DEXA results were consistent with the MRI data. There was no significant rhGH x rosiglitazone interaction for any body composition parameter. The addition of rosiglitazone abrogated the adverse effects of rhGH on insulin sensitivity and glucose tolerance while not significantly modifying the lowering effect of rhGH on VAT. Clinicaltrials.gov NCT00130286.

  18. Multi-species biofilm of Candida albicans and non-Candida albicans Candida species on acrylic substrate

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    Apurva K Pathak

    2012-02-01

    Full Text Available OBJECTIVE: In polymicrobial biofilms bacteria extensively interact with Candida species, but the interaction among the different species of the Candida is yet to be completely evaluated. In the present study, the difference in biofilm formation ability of clinical isolates of four species of Candida in both single-species and multi-species combinations on the surface of dental acrylic resin strips was evaluated. MATERIAL AND METHODS: The species of Candida, isolated from multiple species oral candidiasis of the neutropenic patients, were used for the experiment. Organisms were cultured on Sabouraud dextrose broth with 8% glucose (SDB. Biofilm production on the acrylic resins strips was determined by crystal violet assay. Student's t-test and ANOVA were used to compare in vitro biofilm formation for the individual species of Candida and its different multi-species combinations. RESULTS: In the present study, differences between the mean values of the biofilm-forming ability of individual species (C. glabrata>C. krusei>C. tropicalis>C. albicans and in its multi-species' combinations (the highest for C. albicans with C. glabrata and the lowest for all the four species combination were reported. CONCLUSIONS: The findings of this study showed that biofilm-forming ability was found greater for non-Candida albicans Candida species (NCAC than for C. albicans species with intra-species variation. Presence of C. albicans in multi-species biofilms increased, whereas; C. tropicalis decreased the biofilm production with all other NCAC species.

  19. Relationship between salivary flow rates and Candida albicans counts.

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    Navazesh, M; Wood, G J; Brightman, V J

    1995-09-01

    Seventy-one persons (48 women, 23 men; mean age, 51.76 years) were evaluated for salivary flow rates and Candida albicans counts. Each person was seen on three different occasions. Samples of unstimulated whole, chewing-stimulated whole, acid-stimulated parotid, and candy-stimulated parotid saliva were collected under standardized conditions. An oral rinse was also obtained and evaluated for Candida albicans counts. Unstimulated and chewing-stimulated whole flow rates were negatively and significantly (p Candida counts. Unstimulated whole saliva significantly (p Candida counts of 0 versus or = 500 count. Differences in stimulated parotid flow rates were not significant among different levels of Candida counts. The results of this study reveal that whole saliva is a better predictor than parotid saliva in identification of persons with high Candida albicans counts.

  20. HIV-1 anti-retroviral drug effect on the C. albicans hyphal growth rate by a Bio-Cell Tracer system Efeito da droga anti-retroviral HIV-1 no crescimento de hifas de C. albicans monitoradas pelo sistema "Bio-Cell Tracer"

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    Nadja Rodrigues de Melo

    2006-09-01

    Full Text Available Declining incidence of oropharyngeal candidosis and opportunistic infections over recent years can be attributed to the use of highly active anti-retroviral therapy (HAART. Infection with C. albicans generally involves adherence and colonization of superficial tissues. During this process, budding yeasts are able to transform to hyphae and penetrate into the deep tissue. Using the biocell tracer system, C. albicans hyphal growth was dynamically observed at the cellular level. Ritonavir was effective in the inhibition of hyphal growth with growth rate of 0.8 mum/min. This study showed the in vitro effect of HIV anti-retroviral drug on the growth rate of the C. albicans hyphae.O declínio na incidência de candidose orofaríngea e infecções oportunistas associadas a infecção pelo HIV tem sido atribuído a introdução da terapia antiretroviral combinada (HAART. Infecção por C. albicans envolve aderência e colonização da mucosa superficial. Durante este processo leveduras são capazes de transformar-se na forma de hifas e penetrar nos tecidos mais profundos. Usando o sistema "Bio-Cell Tracer", o crescimento de hifas de C. albicans foi observado dinamicamente a nível celular. Ritonavir, inibidor de protease do HIV, foi efetivo na inibição do crescimento de hifas com media de 0.8 mim/min.O presente estudo demonstrou o efeito in vitro de um agente anti-retroviral HIV sobre o crescimento de hifas de C. albicans.

  1. The interplay between NSAIDs and Candida albicans on the gastrointestinal tract of guinea pigs.

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    Nadăş, George C; Taulescu, Marian A; Ciobanu, Lidia; Fiţ, Nicodim I; Flore, Chirilă; Răpuntean, Sorin; Bouari, Cosmina M; Catoi, Cornel

    2013-04-01

    Recent studies suggest that Candida albicans colonization is associated with several gastrointestinal inflammatory disorders and is also responsible for the delay in ulcer healing. No data are reported about the effects of C. albicans on the nonsteroidal anti-inflammatory drugs (NSAIDs)-induced necroinflammatory lesions. On the other hand, beneficial effects of NSAIDs regarding the colonization potential with C. albicans have been reported. Our aim was to investigate whether the association between NSAIDs and C. albicans could potentially induce necroinflammatory lesions in the guinea pigs gastric and enteral mucosa. Three interventional groups of 11 guinea pigs each were investigated after 5 days of receiving indomethacin, C. albicans or the association of both. C. albicans and necroinflammatory lesions were graded based on histological examinations. Statistical analysis used Mann-Whitney nonparametric test. NSAIDs did not significantly decrease C. albicans colonization grades on gastrointestinal mucosa. Administration of indomethacin subsequent to C. albicans determined significantly more severe necroinflammatory lesions compared to group that only received C. albicans. The association of NSAIDs and C. albicans did not cause significantly more severe degenerative or inflammatory lesions compared to the administration of only NSAIDs in this experimental model. Associations between NSAIDs and C. albicans caused significantly more severe necroinflammatory injuries than the lesions produced by C. albicans, without enhancing the mucosal injury or inflammation caused by NSAIDs.

  2. A radiolabel release microassay for phagocytic killing of Candida albicans

    International Nuclear Information System (INIS)

    Bistoni, F.; Baccarini, M.; Blasi, E.; Marconi, P.; Puccetti, P.

    1982-01-01

    The chromium-51 release technique for quantifying intracellular killing of radiolabelled Candida albicans particles was exploited in a microassay in which murine and human phagocytes acted as effectors under peculiarly simple conditions. At appropriate effector: target ratios and with a 4 h incubation, up to 50% specific chromium release could be detected in the supernatant with no need for opsonization or lysis of phagocytes. This simple microassay permits easy-to-perform, simultaneous testing of a variety of different phagocytes even if only available in limited amounts, and provides an objective measurement of intracellular killing of Candida albicans. (Auth.)

  3. Antifungal and Anti-Biofilm Activities of Acetone Lichen Extracts against Candida albicans

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    Marion Millot

    2017-04-01

    Full Text Available Candida albicans is a commensal coloniser of the human gastrointestinal tract and an opportunistic pathogen, especially thanks to its capacity to form biofilms. This lifestyle is frequently involved in infections and increases the yeast resistance to antimicrobials and immune defenses. In this context, 38 lichen acetone extracts have been prepared and evaluated for their activity against C. albicans planktonic and sessile cells. Minimum inhibitory concentrations of extracts (MICs were determined using the broth microdilution method. Anti-biofilm activity was evaluated using tetrazolium salt (XTT assay as the ability to inhibit the maturation phase (anti-maturation or to eradicate a preformed 24 h old biofilm (anti-biofilm. While none of the extracts were active against planktonic cells, biofilm maturation was limited by 11 of the tested extracts. Seven extracts displayed both anti-maturation and anti-biofilm activities (half maximal inhibitory concentrations IC50_mat and IC50_biof ≤ 100 µg/mL; Evernia prunastri and Ramalina fastigiata were the most promising lichens (IC50_mat < 4 µg/mL and IC50_biof < 10 µg/mL. Chemical profiles of the active extracts performed by thin layer chromatography (TLC and high performance liquid chromatography (HPLC have been analyzed. Depsides, which were present in large amounts in the most active extracts, could be involved in anti-biofilm activities. This work confirmed that lichens represent a reservoir of compounds with anti-biofilm potential.

  4. Distinct stages during colonization of the mouse gastrointestinal tract by Candida albicans

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    Daniel ePrieto

    2015-08-01

    Full Text Available Candida albicans is a member of the human microbiota, colonizing both the vaginal and gastrointestinal tracts. This yeast is devoid of a life style outside the human body and the mechanisms underlying the adaptation to the commensal status remain to be determined. Using a model of mouse gastrointestinal colonization, we show here that C. albicans stably colonizes the mouse gut in about 3 days starting from a dose as low as 100 cells, reaching steady levels of around 107 cells/g of stools. Using fluorescent labeled strains we have assessed the competition between isogenic populations from different sources in cohoused animals. We show that long term (15 days colonizing cells have increased fitness in the gut niche over those grown in vitro or residing in the gut for 1-3 days. Therefore, two distinct states, proliferation and adaptation, seem to exist in the adaptation of this fungus to the mouse gut, a result with potential significance in the prophylaxis and treatment of Candida infections.

  5. Irreversible electropermeabilization of the human pathogen Candida albicans: an in-vitro experimental study.

    Science.gov (United States)

    Novickij, Vitalij; Grainys, Audrius; Svediene, Jurgita; Markovskaja, Svetlana; Paskevicius, Algimantas; Novickij, Jurij

    2015-02-01

    Pathogenic fungi cause many life-threatening infections, especially among individuals with immune system dysfunction. The antifungal drugs commonly used to suppress fungal pathogens can result in long-lasting and toxic therapy. In this work, irreversible electropermeabilization was used to investigate the dynamics of the decrease in Candida albicans colony vitality after application of a pulsed electric field (PEF) and use of antifungal drugs. The fungi were subjected to single 250-µs to 2-ms (0.5-2.5 kV/cm) pulses or repeated short 5-µs pulses, and efficacy was compared. It was shown that electropermeabilization combined with antifungal agents results in rapid and more effective treatment, eliminating more than 90% of C. albicans colony-forming units in a single procedure, which is advantageous in biomedicine. It was also observed that, because of application of PEF and use of the antifungal agents, the Candida cells form cell aggregates and average live cell size is reduced by as much as 53%.

  6. POTENSI EKSTRAK RIMPANG KENCUR (Kaempferia galanga L. MENGHAMBAT PERTUMBUHAN Candida albicans

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    Annisa Rahmi

    2016-12-01

    Full Text Available Candida albicans infection is the cause of candidiasis. Candidiasis treatment can be done with a variety of antifungal drugs, one of them is rhizome of kencur (Kaempferia galanga L.. The Rhizome of kencur is selected as a traditional medicine because it contains chemical compounds such as flavonoids, tannins, saponins and essential oil that serves as an antifungal. This study aimed to determine the minimal inhibitory and minimal killing power and also an influence of kencur rhizome extract on the growth of Candida albicans in vitro. This research was true experimental design with posttest only control group design with tube dilution method. Results of Minimal Inhibitory Concentrations (MICs research showed there was no clarity at concentration of 20 mg/mL, 30 mg/mL, 40 mg/mL, and it shows clarity at concentration of 50 mg/mL and 60 mg/mL. Results of Minimum Bactericidal Concentrations (MBCs showed the number of colonies at concentration of 20 mg/mL were 84 colonies, concentration of 30 mg/mL were 48 colonies, concentration of 40 mg/mL were 27 colonies, concentration of mg/mL were 12 colonies and concentration of 60 mg/mL were 0 colony. Based on linear regression test, the result showed significance value of 0.000

  7. The Role of IL-33 in Host Response to Candida albicans

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    C. Rodríguez-Cerdeira

    2014-01-01

    Full Text Available Background. Interleukin (IL 33 is a recently identified pleiotropic cytokine that influences the activity of multiple cell types and orchestrates complex innate and adaptive immune responses. Methods. We performed an extensive review of the literature published between 2005 and 2013 on IL-33 and related cytokines, their functions, and their regulation of the immune system following Candida albicans colonization. Our literature review included cross-references from retrieved articles and specific data from our own studies. Results. IL-33 (IL-1F11 is a recently identified member of the IL-1 family of cytokines. Accumulating evidence suggests a pivotal role of the IL-33/ST2 axis in host immune defense against fungal pathogens, including C. albicans. IL-33 induces a Th2-type inflammatory response and activates both innate and adaptive immunity. Studies in animal models have shown that Th2 inflammatory responses have a beneficial role in immunity against gastrointestinal and systemic infections by Candida spp. Conclusions. This review summarizes the most important clinical studies and case reports describing the beneficial role of IL-33 in immunity and host defense mechanisms against pathogenic fungi. The finding that the IL-33/ST2 axis is involved in therapeutic target has implications for the prevention and treatment of inflammatory diseases, including acute or chronic candidiasis.

  8. Functional importance of the DNA binding activity of Candida albicans Czf1p.

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    Ivana Petrovska

    Full Text Available The human opportunistic pathogen Candida albicans undergoes a reversible morphological transition between the yeast and hyphal states in response to a variety of signals. One such environmental trigger is growth within a semisolid matrix such as agar medium. This growth condition is of interest because it may mimic the growth of C. albicans in contact with host tissue during infection. During growth within a semisolid matrix, hyphal growth is positively regulated by the transcriptional regulator Czf1p and negatively by a second key transcriptional regulator, Efg1p. Genetic studies indicate that Czf1p, a member of the zinc-cluster family of transcriptional regulators, exerts its function by opposing the inhibitory influence of Efg1p on matrix-induced filamentous growth. We examined the importance of the two known activities of Czf1p, DNA-binding and interaction with Efg1p. We found that the two activities were separable by mutation allowing us to demonstrate that the DNA-binding activity of Czf1p was essential for its role as a positive regulator of morphogenesis. Surprisingly, however, interactions with Efg1p appeared to be largely dispensable. Our studies provide the first evidence of a key role for the DNA-binding activity of Czf1p in the morphological yeast-to-hyphal transition triggered by matrix-embedded growth.

  9. Silver colloidal nanoparticles: effect on matrix composition and structure of Candida albicans and Candida glabrata biofilms.

    Science.gov (United States)

    Monteiro, D R; Silva, S; Negri, M; Gorup, L F; de Camargo, E R; Oliveira, R; Barbosa, D B; Henriques, M

    2013-04-01

    The aim of this study was to assess the effect of different silver nanoparticles (SN) concentrations on the matrix composition and structure of Candida albicans and Candida glabrata biofilms. Candida biofilms were developed in 6-well microtiter plates during 48 h. After, these biofilms were exposed to 13.5 or 54 μg SN ml(-1) for 24 h. Then, extracellular matrices were extracted from biofilms and analysed chemically in terms of proteins, carbohydrates and DNA. To investigate the biofilm structure, scanning electron microscopy (SEM) and epifluorescence microscopy were used. SN interfered with the matrix composition of Candida biofilms tested in terms of protein, carbohydrate and DNA, except for the protein content of C. albicans biofilm. By SEM, Candida biofilms treated with SN revealed structural differences, when compared with the control groups. Further, SN showed a trend of agglomeration within the biofilms. Epifluorescence microscopy images suggest that SN induced damage on cell walls of the Candida isolates tested. In general, irrespective of concentration, SN affected the matrix composition and structure of Candida biofilms and these findings may be related to the mechanisms of biocide action of SN. This study reveals new insights about the behaviour of SN when in contact with Candida biofilms. SN may contribute to the development of therapies to prevent or control Candida infections. © 2012 The Society for Applied Microbiology.

  10. Reduction in deformed wing virus infection in larval and adult honey bees (Apis mellifera L.) by double-stranded RNA ingestion.

    Science.gov (United States)

    Desai, S D; Eu, Y-J; Whyard, S; Currie, R W

    2012-08-01

    Deformed wing virus (DWV) is a serious pathogen of the honey bee, Apis mellifera L., vectored by the parasitic mite Varroa destructor. The virus is associated with wing deformity in symptomatic bees, and premature death and reduced colony performance in asymptomatic bees. In the present study we reduced DWV infection by feeding both first instar larvae and adult A. mellifera with a double-stranded (ds) RNA construct, DWV-dsRNA, which is specific to DWV in DWV-inoculated bees, by mixing it with their food. We showed that feeding DWV to larvae causes wing deformity in adult bees in the absence of varroa mites and decreases survival rates of adult bees relative to bees not fed DWV. Feeding larvae with DWV-dsRNA in advance of inoculation with virus reduced the DWV viral level and reduced wing deformity relative to larvae fed DWV or DWV with green fluorescent protein-dsRNA (probably a result of RNA silencing), but did not affect survival to the adult stage. Feeding DWV-dsRNA did not affect larval survival rates, which suggests that dsRNA is non-toxic to larvae. Feeding adult workers with DWV-dsRNA in advance of inoculation with virus increased their longevity and reduced DWV concentration relative to controls. © 2012 The Authors. Insect Molecular Biology © 2012 The Royal Entomological Society.

  11. Invitro Anti-mycotic Activity of Hydro Alcoholic Extracts of Some Indian Medicinal Plants against Fluconazole Resistant Candida albicans.

    Science.gov (United States)

    Varadarajan, Saranya; Narasimhan, Malathi; Malaisamy, Malaiyandi; Duraipandian, Chamundeeswari

    2015-08-01

    Candidiasis is one of the most common opportunistic infections caused by Candida albicans. Fluconazole is the drug of choice for prevention and management of this condition. However, the emergence of fluconazole resistant candidal strains has become a major concern. Many herbs like fenugreek, cinnamon, papaya, oregano, garlic are rich in phytochemical constituents known to express antimycotic activity. With the available information, the present research study was carried out to assess the invitro anti-mycotic activity of hydro alcoholic extracts of Trigonella foenum-graecum seeds, Cinnamomum verum bark and Carica papaya leaves and seeds against fluconazole resistant Candida albicans. Hydro alcoholic extracts of Trigonella foenum-graecum (seeds), Cinnamomum verum (bark), Carica papaya CO.2 strain (male and female leaves) and Carica papaya CO.2 strain (seeds) were prepared by maceration. The anti-mycotic activity of the prepared extracts against Candida albicans was assessed by agar well diffusion method. Three independent experiments were performed in triplicates and the mean and standard deviation were calculated. Minimum inhibitory concentration was determined. The results of the present study revealed that all the extracts exhibited anti-mycotic activity in a dose dependent manner and minimum inhibitory concentration of all the extracts was found to be 15.62 μg/ml. The results of the present study shed light on the fact that plant extracts could be used not only as an alternate drug for management of fluconazole resistant candidiasis but also explored further for oral cancer prevention as a therapeutic adjunct.

  12. DETECTION OF ANTIBODIES TO CANDIDA ALBICANS GERM TUBE BY IMMUNOFLUORESCENCE IN IMMUNOSUPPRESSED MICE WITH EXPERIMENTAL SYSTEMIC CANDIDIASIS

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    F. Zaini

    2007-07-01

    Full Text Available "nThe increasing incidence of systemic candidiasis, which parallels the use of invasive and immunosuppressive medical procedures, necessitates development of rapid and cost effective tests for diagnosis of systemic candidiasis. Therefore in this study 85 mice were first immunosuppressed by cyclophosphamide and then infected by Candida albicans NCPF 3153. Other 85 mice were employed as control. The case and control mice were bled and then autopsied. Hearts and kidneys were checked by direct, histopathological and cultural examination for systemic candidiasis. The 85 sera from histological proven cases and 85 control mice were adsorbed with heat killed blastospores of same strain of C. albicans. Anti-Candida albicans germ tube antibodies were detected by indirect immunofluorescence assay for diagnosis of invasive candidiasis in case and control mice. In addition, sera from 35 mice with proven cryptococcosis were also tested. While 84 mice with proven systemic candidiasis (100% had anti-germ tube antibodies, these antibodies were absent in all controls and mice with cryptococcosis. The specificity was 100%, indicating a high degree of discrimination was possible between systemic candidiasis and cryptococcosis in the mice studied. It must be concluded that anti-germ tube responses did not appear to be significantly reduced in immunocompromised mice.

  13. Modelling the host-pathogen interactions of macrophages and Candida albicans using Game Theory and dynamic optimization.

    Science.gov (United States)

    Dühring, Sybille; Ewald, Jan; Germerodt, Sebastian; Kaleta, Christoph; Dandekar, Thomas; Schuster, Stefan

    2017-07-01

    The release of fungal cells following macrophage phagocytosis, called non-lytic expulsion, is reported for several fungal pathogens. On one hand, non-lytic expulsion may benefit the fungus in escaping the microbicidal environment of the phagosome. On the other hand, the macrophage could profit in terms of avoiding its own lysis and being able to undergo proliferation. To analyse the causes of non-lytic expulsion and the relevance of macrophage proliferation in the macrophage- Candida albicans interaction, we employ Evolutionary Game Theory and dynamic optimization in a sequential manner. We establish a game-theoretical model describing the different strategies of the two players after phagocytosis. Depending on the parameter values, we find four different Nash equilibria and determine the influence of the systems state of the host upon the game. As our Nash equilibria are a direct consequence of the model parameterization, we can depict several biological scenarios. A parameter region, where the host response is robust against the fungal infection, is determined. We further apply dynamic optimization to analyse whether macrophage mitosis is relevant in the host-pathogen interaction of macrophages and C. albicans For this, we study the population dynamics of the macrophage- C. albicans interactions and the corresponding optimal controls for the macrophages, indicating the best macrophage strategy of switching from proliferation to attacking fungal cells. © 2017 The Author(s).

  14. The AAA ATPase Vps4 Plays Important Roles in Candida albicans Hyphal Formation and is Inhibited by DBeQ.

    Science.gov (United States)

    Zhang, Yahui; Li, Wanjie; Chu, Mi; Chen, Hengye; Yu, Haoyuan; Fang, Chaoguang; Sun, Ningze; Wang, Qiming; Luo, Tian; Luo, Kaiju; She, Xueping; Zhang, Mengqian; Yang, Dong

    2016-06-01

    Candida albicans is an opportunistic human pathogen, and its pathogenicity is associated with hyphal formation. Previous studies have shown that at neutral-to-alkaline pH, hyphal growth is dependent on the Rim101 pathway whose activation requires Snf7, a member of the ESCRT system. In this work, we described the purification and characterization of the C. albicans Vps4, an AAA ATPase required for recycling of the ESCRTs. Its role on hyphal growth has been investigated. Our data suggest deletion of Vps4 decreases overall hyphal growth at pH 7 and increases the growth of multiple hyphae induced by serum, which indicates that the ESCRTs may make a Rim101-independent contribution to hyphal growth. Furthermore, DBeQ, an inhibitor of the AAA ATPase p97, was shown to inhibit the ATPase activity of Vps4 with an IC50 of about 11.5 μM. To a less degree, it also inhibits hyphal growth. Our work may provide a new strategy to control C. albicans infection.

  15. The Mkk2 MAPKK Regulates Cell Wall Biogenesis in Cooperation with the Cek1-Pathway in Candida albicans.

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    Elvira Román

    Full Text Available The cell wall integrity pathway (CWI plays an important role in the biogenesis of the cell wall in Candida albicans and other fungi. In the present work, the C. albicans MKK2 gene that encodes the putative MAPKK of this pathway was deleted in different backgrounds and the phenotypes of the resultant mutants were characterised. We show here that Mkk2 mediates the phosphorylation of the Mkc1 MAPK in response to cell wall assembly interfering agents such as zymolyase or tunicamycin and also to oxidative stress. Remarkably, mkk2 and mkc1 mutants display related but distinguishable- cell wall associated phenotypes and differ in the pattern of MAPK phosphorylation under different stress conditions. mkk2 and mkc1 mutants display an altered expression of GSC1, CEK1 and CRH11 genes at different temperatures. Combined deletion of MKK2 with HST7 supports a cooperative role for the Cek1-mediated and CWI pathways in regulating cell wall architecture under vegetative growth. However, and in contrast to Mkc1, Mkk2 does not seem to play a role in the virulence of C. albicans in the mouse systemic model or the Galleria mellonella model of infection.

  16. Genetic relatedness among vaginal and anal isolates of Candida albicans from women with vulvovaginal candidiasis in north-east Brazil.

    Science.gov (United States)

    Araújo Paulo de Medeiros, Mariana; Vieira de Melo, Ana Patrícia; Gonçalves, Sarah Santos; Milan, Eveline Pipolo; Chaves, Guilherme Maranhão

    2014-11-01

    Vulvovaginal candidiasis (VVC) is one of the most common causes of vaginitis and affects about 75% of women of reproductive age. In order to better understand the epidemiology and pathogenesis of this disease, we evaluated genetic relatedness among 62 clinical isolates of Candida albicans sequentially obtained from the anus and vagina of patients with sporadic and recurrent VVC. Evaluation of patients' demographic and clinical data, direct examination, and colony forming units (c.f.u.) counts of vaginal and anal samples were also performed. The genotypes of strains were determined with ABC genotyping and Randomly Amplified Polymorphic DNA (RAPD). Genotype A was the most prevalent (93.6%), followed by genotype C (6.4%), whereas genotype B was not found. We found the maintenance of the same ABC genotype, regardless of the body site of each patient. Most of the vaginal strains suffered microevolution, whereas most of the anal strains were replaced during the period of study. Vaginal and anal isolates of C. albicans obtained simultaneously from the same patient showed the same ABC genotype and high genetic similarity as determined by RAPD. Genotype A seemed to be dominant in both vaginal and anal isolates of patients with VVC. Our results corroborate the hypothesis that there are 'substrains' of the C. albicans vaginal clone successfully established, which dominate in an apparently random manner over the course of time. It is suggested that the anal reservoir constitutes a possible source for vaginal infection in most of the cases. © 2014 The Authors.

  17. The Candida albicans Ddr48 protein is essential for filamentation, stress response, and confers partial antifungal drug resistance.

    Science.gov (United States)

    Dib, Leila; Hayek, Peter; Sadek, Helen; Beyrouthy, Berna; Khalaf, Roy A

    2008-06-01

    Candida albicans is a dimorphic pathogenic fungus that causes mucosal and systemic infections. C. albicans pathogenicity is attributed to its ability to exist in different morphologic states and to respond to stress by up regulating several key genes. DDR48 is a stress-associated gene involved in DNA repair and in response to antifungal drug exposure. One allele of DDR48 was knocked out by homologous recombination that inserted a marker cassette in its position. Furthermore, reintroducing DDR48 on a plasmid created a revertant strain. Strains were grown on filamentation inducing and noninducing media, subjected to an oxidative stress challenge, injected into mice to assess virulence, and assayed for antifungal susceptibility by the E-test method. DDR48 was found to be haploid insufficient and possibly essential, since only a heterozygote, but not a homozygous, null mutant was generated. The mutant was filamentation defective on all hyphal media tested including serum and corn meal agar. Discrepancies in drug resistance profiles also were present: compared with the parental strain, DDR48/ddr48 heterozygote strain was susceptible in a dose-dependent manner to itraconazole and fluconazole and susceptible to ketoconazole. The mutant also appeared to be hypersensitive to a potentially lethal hydrogen peroxide challenge. However, no reduction in virulence of the mutant was observed. The present findings provide evidence that DDR48 is essential for filamentation, stress response, and possibly viability of C. albicans, making it a prime target for antifungal drug design.

  18. Antifungal Effects of Gold Nanoparticles Conjugated Fluconazole against Fluconazole Resistant Strains of Candida albicans Isolated From Patients with Chronic Vulvovaginitis

    Directory of Open Access Journals (Sweden)

    Mehrdad Memarian

    2016-09-01

    Full Text Available Background and Objectives: A number of women with volvuvaginal candidiasis suffer from certain chronic and recurrent types of this infection that affect their quality of life. Meanwhile, increased use of antifungal drugs, especially azoles, for treatment of chronic candidiasis is an important factor for incidence of drug resistance in Candida isolates from patients with vulvovaginal candidiasis. The aim of this study was to investigate anticandidal effects of gold nanoparticles conjugated fluconazole to develop better drugs for treatment of patients with candidal vaginitis, especially its chronic type. Methods: After collection of 300 vaginal swab specimens and culture and isolation of primary colonies and determination of Candida species, fluconazole resistant strains of Candida albicans were detected using disc diffusion. Finally, antifungal effects of gold nanoparticles conjugated fluconazole and fluconazole were compared by broth microdilution. Results: Only one fluconazole resistant strain of C. albicans was isolated from patients (MIC=64µg/ml. The results obtained from drug susceptibility test showed that this strain was sensitive to gold nanoparticles conjugated fluconazole (MIC=2µg/ml. Conclusion: Given the optimal anticandidal effects of gold nanoparticles conjugated fluconazole on resistant strains of C. albicans, a suitable compound with great anticandidal properties may be achieved in the future.

  19. The Discovery of a Potential Antimicrobial Agent: the Novel Compound Natural Medicinal Plant Fermentation Extracts against Candida albicans

    Science.gov (United States)

    Song, Mingzhu; Wang, Xirui; Mao, Canquan; Yao, Wei

    2018-01-01

    Natural medicinal plants and their extracts are important sources of antimicrobial drug development. In this study, we reported an ancient formula of Chinese folk medicine, the compound natural medicinal plant fermentation extracts (CNMPFE) for its antimicrobial effects. The effects and mechanisms of CNMPFE on C. albicans were studied by cell damage experiments including antimicrobial kinetics, fungal growth curve, alkaline phosphatase (AKP) activity, ultraviolet absorption, electric conductivity and the evaluation of cellular ultra microstructure. The results showed that the minimal inhibitory concentration and minimum fungicidal concentration of CNMPFE against C. albicans were 75% (vol/vol) and 80% (vol/vol) respectively. The inhibition of CNMPFE for C. albicans was dose and time dependent, based on increasing of the AKP activities and the ultraviolet absorptions and the electric conductivities of the fungal solutions, it may exert its antifungal properties by disrupting the structure of cell wall and the cell membrane integrity and their permeability, subsequently resulting in cell death. Taken together, these findings suggest that CNMPFE may be a promising drug candidate for the treatment of fungal infections skin diseases.

  20. The comparative study of antifungal activity of Syzygium aromaticum, Punica granatum and nystatin on Candida albicans; an in vitro study.

    Science.gov (United States)

    Mansourian, A; Boojarpour, N; Ashnagar, S; Momen Beitollahi, J; Shamshiri, A R

    2014-12-01

    Candida species are opportunistic fungi, among which, Candida albicans is the most important species responsible for infections in immunocompromised patients with invasive fungal disease. Resistance of Candida species to antifungal drugs has led scientists to pay more attention to traditional medicine herbs. Due to the limitations in the treatment of fungal diseases such as shortages, high prices, antifungal side effects and drug resistance or reduced susceptibility to fungal drugs we decided to study the antifungal effects of herbal extracts of Syzygium aromaticum and Punica granatum. Twenty-one isolates of oral C. albicans in patients with denture stomatitis referred to prosthesis department, Dental faculty of Tehran University of Medical Sciences were prepared and cultured. Plant extracts were prepared from the herbs market. Tests on patient samples and standard strains 5027ATCC (PTCC10231) yeast C. albicans were performed via well diffusion method. In addition, nystatin and methanol were used as positive and negative control, respectively. Finally, the antifungal effect of extracts using Statistical Repeated measurement ANOVA test was investigated. Both S. aromaticum and P. granatum showed noticeable antifungal activity in well method. Syzygium aromaticum showed better anti candida activity than nystatin (Pgranatum showed good antifungal effects (P-value<0.001). S. aromaticum (inhibition zone diameter: 29.62) showed better antifungal effects than nystatin (inhibition zone diameter: 28.48). Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  1. Genome-wide fitness test and mechanism-of-action studies of inhibitory compounds in Candida albicans.

    Directory of Open Access Journals (Sweden)

    Deming Xu

    2007-06-01

    Full Text Available Candida albicans is a prevalent fungal pathogen amongst the immunocompromised population, causing both superficial and life-threatening infections. Since C. albicans is diploid, classical transmission genetics can not be performed to study specific aspects of its biology and pathogenesis. Here, we exploit the diploid status of C. albicans by constructing a library of 2,868 heterozygous deletion mutants and screening this collection using 35 known or novel compounds to survey chemically induced haploinsufficiency in the pathogen. In this reverse genetic assay termed the fitness test, genes related to the mechanism of action of the probe compounds are clearly identified, supporting their functional roles and genetic interactions. In this report, chemical-genetic relationships are provided for multiple FDA-approved antifungal drugs (fluconazole, voriconazole, caspofungin, 5-fluorocytosine, and amphotericin B as well as additional compounds targeting ergosterol, fatty acid and sphingolipid biosynthesis, microtubules, actin, secretion, rRNA processing, translation, glycosylation, and protein folding mechanisms. We also demonstrate how chemically induced haploinsufficiency profiles can be used to identify the mechanism of action of novel antifungal agents, thereby illustrating the potential utility of this approach to antifungal drug discovery.

  2. Creatine fails to augment the benefits from resistance training in patients with HIV infection: a randomized, double-blind, placebo-controlled study.

    Directory of Open Access Journals (Sweden)

    Giorgos K Sakkas

    Full Text Available Progressive resistance exercise training (PRT improves physical functioning in patients with HIV infection. Creatine supplementation can augment the benefits derived from training in athletes and improve muscle function in patients with muscle wasting. The objective of this study was to determine whether creatine supplementation augments the effects of PRT on muscle strength, energetics, and body composition in HIV-infected patients.This is a randomized, double blind, placebo-controlled, clinical research center-based, outpatient study in San Francisco. 40 HIV-positive men (20 creatine, 20 placebo enrolled in a 14-week study. Subjects were randomly assigned to receive creatine monohydrate or placebo for 14 weeks. Treatment began with a loading dose of 20 g/day or an equivalent number of placebo capsules for 5 days, followed by maintenance dosing of 4.8 g/day or placebo. Beginning at week 2 and continuing to week 14, all subjects underwent thrice-weekly supervised resistance exercise while continuing on the assigned study medication (with repeated 6-week cycles of loading and maintenance. The main outcome measurements included muscle strength (one repetition maximum, energetics ((31P magnetic resonance spectroscopy, composition and size (magnetic resonance imaging, as well as total body composition (dual-energy X-ray absorptiometry. Thirty-three subjects completed the study (17 creatine, 16 placebo. Strength increased in all 8 muscle groups studied following PRT, but this increase was not augmented by creatine supplementation (average increase 44 vs. 42%, difference 2%, 95% CI -9.5% to 13.9% in creatine and placebo, respectively. There were no differences between groups in changes in muscle energetics. Thigh muscle cross-sectional area increased following resistance exercise, with no additive effect of creatine. Lean body mass (LBM increased to a significantly greater extent with creatine. CONCLUSIONS / SIGNIFICANCE: Resistance exercise improved

  3. Standardised high dose versus low dose cranberry Proanthocyanidin extracts for the prevention of recurrent urinary tract infection in healthy women [PACCANN]: a double blind randomised controlled trial protocol.

    Science.gov (United States)

    Asma, Babar; Vicky, Leblanc; Stephanie, Dudonne; Yves, Desjardins; Amy, Howell; Sylvie, Dodin

    2018-05-02

    Urinary tract infections (UTIs) are amongst the most common bacterial infections affecting women. Although antibiotics are the treatment of choice for UTI, cranberry derived products have been used for many years to prevent UTIs, with limited evidence as to their efficacy. Our objective is to assess the efficacy of a cranberry extract capsule standardized in A-type linkage proanthocyanidins (PACs) for the prevention of recurrent urinary tract infection. We will perform a 1:1 randomized, controlled, double blind clinical trial in women aged 18 years or more who present ≥2 UTIs in 6 months or ≥ 3 UTIs in 12 months. One hundred and forty-eight women will be recruited and randomized in two groups to either receive an optimal dose of cranberry extract quantified and standardized in PACs (2 × 18.5 mg PACs per day) or a control dose (2 × 1 mg PACs per day). The primary outcome for the trial is the mean number of new symptomatic UTIs in women during a 6-month intervention period. Secondary outcomes are: (1) To evaluate the mean number of new symptomatic UTIs with pyuria as demonstrated by a positive leucocyte esterase test; (2) To detect the mean number of new symptomatic culture-confirmed UTIs; (3) To quantify urinary PACs metabolites in women who take a daily dose of 37 mg PACs per day compared to women who take a daily dose of 2 mg per day for 6 months; (4) To characterize women who present recurrent UTI based on known risk factors for recurrent UTI; (5) To describe the side effects of daily intake of cranberry extract containing 37 mg PACs compared to 2 mg PACs. This report provides comprehensive methodological data for this randomized controlled trial. The results of this trial will inform urologists, gynaecologists, family physicians and other healthcare professionals caring for healthy women with recurrent UTI, as to the benefits of daily use of an optimal dose of cranberry extract for the prevention of recurrent UTI. Clinicaltrials

  4. Growth inhibitory action of ebselen on fluconazole-resistant Candida albicans: role of the plasma membrane H+-ATPase.

    Science.gov (United States)

    Billack, Blase; Santoro, Michelle; Lau-Cam, Cesar

    2009-06-01

    PMA1 is a yeast gene that codes for the plasma membrane H(+)-ATPase, a protein commonly referred to as Pma1p. Ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) is a synthetic selenium-containing compound that has recently been shown to display antimicrobial activity owing to its ability to inhibit Pma1p. Ebselen is able to block the activity of Pma1p not only in opportunistic pathogens such as Cryptococcus neoformans and Candida albicans but also in nonpathogenic yeasts such as Saccharomyces cerevisiae. A series of in vitro studies aimed at evaluating the antifungal activity of ebselen were performed. At low concentrations (ebselen was fungistatic against three strains of S. cerevisiae (IC(50) approximately 3 microM) and one fluconazole-resistant strain of C. albicans (IC(50) approximately 6 microM), and at a high concentration (30 microM) it was fungicidal against C. albicans. Moreover, ebselen was found to inhibit medium acidification by the fluconazole-resistant strain of C. albicans in a concentration-dependent manner. In comparison to currently used antifungal agents represented by azole (itraconazole, ketoconazole, fluconazole) and polyene (amphotericin B) compounds, ebselen was at least 10-fold more potent than fluconazole but less active than the other compounds tested. The present results suggest that the growth inhibitory activity of ebselen toward fluconazole-resistant yeast cells is due, at least in part, to inhibition of Pma1p. Ebselen may also serve as a useful agent in the treatment of infections caused by fluconazole-resistant fungi.

  5. Identification of Candida Species Using MP65 Gene and Evaluation of the Candida albicans MP65 Gene Expression in BALB/C Mice.

    Science.gov (United States)

    Bineshian, Farahnaz; Yadegari, Mohammad Hossien; Sharifi, Zohre; Akbari Eidgahi, Mohammadreza; Nasr, Reza

    2015-05-01

    ). All species isolated by culture methods (100% positivity) were evaluated with PCR using species-specific primers to identify Candida species. Relative expression of Mp65 genes increased significantly after C. albicans injection into the mice (P < 0.05). The results of the current study showed that the PCR method is reproducible for rapid identification of Candida species with specific primers. Mp65 gene expression of C. albicans after injection into the mice was 2.3 folds higher than before injection, with this difference being significant. These results indicated that increase of Mp65 gene expression might be an early stage of infection; however definitive conclusions require further studies.

  6. Evaluation of Candida Albicans Biofilm Formation on Various Parts ...

    African Journals Online (AJOL)

    2018-02-07

    Feb 7, 2018 ... Aims: Candida albicans adhesion to any oral substrata is the first and essential stage in forming a .... kinds of resin, glass, and even metal surfaces.[14] ... various parts of implant materials [tissue level implant, bone level ...

  7. EFEITO ANTIFÚNGICO DO RESVERATROL SOBRE A CANDIDA ALBICANS

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    Bruna Graziele Marques da Silva

    2017-05-01

    Full Text Available A Candida albicans é um fungo comensal da microbiota normal, sendo capaz de produzir infecções em pacientes imunocomprometidos. As infecções estão apresentando resistência às terapias convencionais. Recentemente diversos compostos derivados de produtos naturais vêm sendo testados, destacando o polifenol Resveratrol que possui efeitos farmacológicos. Desse modo o objetivo deste estudo foi avaliar os efeitos do polifenol sobre o crescimento e a viabilidade do biofilme da C. albicans. Foram utilizadas as concentrações do Resveratrol em 5 μΜ, 10 μΜ, 20 μΜ, 50 μΜ, 100 μΜ, 200 μΜ, 300μΜ, 400μΜ e 500μΜ e a densidade de C.albicans foram de 105, 106 e 107 células viáveis/ml, e ainda, foi analisada a morfologia. Os resultados obtidos demonstram maior inibição no crescimento e viabilidade do biofilme na concentração de 500μΜ de polifenol, em comparação ao controle. Dessa forma, o polifenol Resveratrol foi capaz de alterar a morfologia das células e reduzir a viabilidade do biofilme da Candida albicans.

  8. Evaluation of Candida albicans biofilm formation on various dental ...

    African Journals Online (AJOL)

    Evaluation of Candida albicans biofilm formation on various dental restorative material surfaces. ... Nigerian Journal of Clinical Practice ... was significantly lower on the resin-modified glass ionomer and glass-ionomer cement samples. ... Conclusion: This finding emphasizes the use of glass ionomer restorative cements and ...

  9. Candida albicans colonisation, continence status and incontinence-associated dermatitis in the acute care setting: a pilot study.

    Science.gov (United States)

    Campbell, Jill L; Coyer, Fiona M; Mudge, Alison M; Robertson, Ivan M; Osborne, Sonya R

    2017-06-01

    Candida albicans is the most prevalent human fungal commensal organism and is reported to be the most frequent aetiological organism responsible for infection associated with incontinence-associated dermatitis. However, it remains unclear whether incontinence predisposes a patient to increased Candida colonisation or whether incontinence acts as a trigger for Candida infection in those already colonised. The purpose of this observational cross-sectional study was to estimate colonisation rates of C. albicans in continent, compared to incontinent patients, and patients with incontinence-associated dermatitis. Data were collected on 81 inpatients of a major Australian hospital and included a pelvic skin inspection and microbiological specimens to detect C. Albicans at hospital admission. The mean age of the sample was 76 years (SD = 12.22) with 53% being male. Incontinent participants (n = 53) had a non-significant trend towards greater Candida colonisation rates at the perianal site (43% versus 28%) χ 2 (1, N = 81) = 4·453, p = ·638 and the inguinal site (24% versus 14%) χ 2 (1, N = 81) = 6·868, p = ·258 compared to continent patients (n = 28). The incontinent subgroup with incontinence-associated dermatitis (n = 22) showed no difference in colonisation rates compared to those without incontinence-associated dermatitis. Understanding the epidemiology of colonisation may have implications for the prevention of Candida infection in these patients. © 2016 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  10. The effect of parenteral alimentation fluid, undiluted with saline or fresh sera, on the growth of Candida albicans in vitro at 37 degrees C.

    Science.gov (United States)

    Lederer, T; Rippon, J; Baldwin, S; Pachman, L M

    1975-02-28

    Parenteral alimentation is often complicated by Candida albicans infection which may be fatal. This study investigated the effect of alimentation fluid (Aminosol) on C. albicans' growth in vitro. It was found that concentrated Aminosol (1400 millisomoles) maintained C. albicans in a viable state but inhibited replication. Dilution of alimentation fluid to physiological concentrations (300 milliosmoles) with either saline or aged pooled normal sera promoted in vitro growth of C. albicans which was equivalent to that obtained in BHI broth and was slightly less than that obtained in Sabouraud's broth. The effects of fresh sera with full complement activity were also investigated. In fresh sera appropriately diluted with physiological saline, some clumping of the yeasts was observed and all formed germ tubes. Growth as defined by budding or the formation of hyphae was inhibited. When Aminosol was diluted to 300 milliosomoles with fresh sera, all yeasts were noted to be in clumps with germ tubes as well as continually growing hyphae. Growth was approximately equal to that seen in Aminosol similarly diluted with saline.

  11. Expression, crystallization and preliminary X-ray data analysis of NT-Als9-2, a fungal adhesin from Candida albicans

    International Nuclear Information System (INIS)

    Salgado, Paula S.; Yan, Robert; Rowan, Fiona; Cota, Ernesto

    2011-01-01

    Details of the expression and crystallization of the N-terminal fragment of Als9-2, an adhesin from the human commensal/pathogenic fungus C. albicans, are reported. Preliminary analysis of the collected X-ray data is also discussed. Candida albicans is a common human fungal commensal that can also cause a range of infections from skin/mucosal ‘thrush’ to severe systemic candidiasis. Adherence to host cells is one of the key determinants of Candida pathogenesis. The Als family of surface proteins has been implicated in adhesion of C. albicans, yet limited information has been published on the structure and mechanism of these fungal adhesins. The N-terminal region of these proteins has been shown to possess adhesive properties, making it a possible target for new therapeutic strategies. Recombinant NT-Als9-2 from C. albicans (residues 18–329) was overexpressed in Escherichia coli, purified and crystallized. Diffraction data were collected to 2.0 Å resolution. The crystals belonged to space group P2 1 2 1 2 1 , with unit-cell parameters a = 34.73, b = 68.71, c = 120.03 Å, α = β = γ = 90° and one molecule in the asymmetric unit. Platinum-derivatized crystals belonged to the same space group, with similar unit-cell parameters, although they were not completely isomorphous

  12. Complementation of Saccharomyces cerevisiae mutations in genes involved in translation and protein folding (EFB1 and SSB1) with Candida albicans cloned genes.

    Science.gov (United States)

    Maneu, V; Roig, P; Gozalbo, D

    2000-11-01

    We have demonstrated that the expression of Candida albicans genes involved in translation and protein folding (EFB1 and SSB1) complements the phenotype of Saccharomyces cerevisiae mutants. The elongation factor 1beta (EF-1beta) is essential for growth and efb1 S. cerevisiae null mutant cells are not viable; however, viable haploid cells, carrying the disrupted chromosomal allele of the S. cerevisiae EFB1 gene and pEFB1, were isolated upon sporulation of a diploid strain which was heterozygous at the EFB1 locus and transformed with pEFB1 (a pEMBLYe23 derivative plasmid containing an 8-kb DNA fragment from the C. albicans genome which contains the EFB1 gene). This indicates that the C. albicans EFB1 gene encodes a functional EF-1beta. Expression of the SSB1 gene from C. albicans, which codes for a member of the 70-kDa heat shock protein family, in S. cerevisiae ssb1 ssb2 double mutant complements the mutant phenotype (poor growth particularly at low temperature, and sensitivity to certain protein synthesis inhibitors, such as paromomycin). This complementation indicates that C. albicans Ssbl may function as a molecular chaperone on the translating ribosomes, as described in S. cerevisiae. Northern blot analysis showed that SSB mRNA levels increased after mild cold shift (28 degrees C to 23 degrees C) and rapidly decreased after mild heat shift (from 28 degrees C to 37 degrees C, and particularly to 42 degrees C), indicating that SSB1 expression is regulated by temperature. Therefore, Ssb1 may be considered as a molecular chaperone whose pattern of expression is similar to that found in ribosomal proteins, according to its common role in translation.

  13. Estrogen Receptor-Alpha (ESR1) Governs the Lower Female Reproductive Tract Vulnerability to Candida albicans

    Science.gov (United States)

    Salinas-Muñoz, Laura; Campos-Fernández, Raúl; Mercader, Enrique; Olivera-Valle, Irene; Fernández-Pacheco, Carlota; Matilla, Lara; García-Bordas, Julio; Brazil, Jennifer C.; Parkos, Charles A.; Asensio, Fernando; Muñoz-Fernández, Maria A.; Hidalgo, Andrés; Sánchez-Mateos, Paloma; Samaniego, Rafael; Relloso, Miguel

    2018-01-01

    Estradiol-based therapies predispose women to vaginal infections. Moreover, it has long been known that neutrophils are absent from the vaginal lumen during the ovulatory phase (high estradiol). However, the mechanisms that regulate neutrophil influx to the vagina remain unknown. We investigated the neutrophil transepithelial migration (TEM) into the vaginal lumen. We revealed that estradiol reduces the CD44 and CD47 epithelial expression in the vaginal ectocervix and fornix, which retain neutrophils at the apical epithelium through the estradiol receptor-alpha. In contrast, luteal progesterone increases epithelial expression of CD44 and CD47 to promote neutrophil migration into the vaginal lumen and Candida albicans destruction. Distinctive to vaginal mucosa, neutrophil infiltration is contingent to sex hormones to prevent sperm from neutrophil attack; although it may compromise immunity during ovulation. Thus, sex hormones orchestrate tolerance and immunity in the vaginal lumen by regulating neutrophil TEM. PMID:29881378

  14. The effect of Helicobacter pylori infection and eradication in patients with gastro-oesophageal reflux disease: A parallel-group, double-blind, placebo-controlled multicentre study.

    Science.gov (United States)

    Schwizer, Werner; Menne, Dieter; Schütze, Kurt; Vieth, Michael; Goergens, Reiner; Malfertheiner, Peter; Leodolter, Andreas; Fried, Michael; Fox, Mark R

    2013-08-01

    This study aimed to resolve controversy regarding the effects of Helicobacter pylori eradication therapy and H. pylori infection in gastro-oesophageal reflux disease. A randomized, double-blind, multicentre trial was performed in patients presenting with reflux symptoms. H. pylori-positive patients were randomized to receive either antibiotics or placebo for 7 days. H. pylori-negative patient controls received placebo. All received esomeprazole 20 mg b.d. for 7 days, followed by 40 mg o.d. to complete an 8-week course, and were followed up for 32 weeks by telephone. In this study, 198/589 (34%) patients were H. pylori-positive and 113 H. pylori-negative patients served as controls. Baseline endoscopy revealed 63% Los Angeles grade 0A and 37% Los Angeles grade BCD oesophagitis with no difference between patient groups. Symptom improvement on esomeprazole was seen in 89%. H. pylori eradication was successful in 82%. H. pylori eradication had no effect on symptomatic relapse (hazard ratio 1.15, 95% CI 0.74-1.8; p = 0.5). Overall, H. pylori-positive patients had a lower probability of relapse compared to H. pylori-negative controls (hazard ratio 0.6, 95% CI 0.43-0.85; p = 0.004). Relapse hazard was modulated also by oesophagitis grade (BCD vs. 0A, hazard ratio 2.1, 95% CI 1.5-3.0). Relapse of gastro-oesophageal reflux disease symptoms after a course of high dose acid suppression took longer for H. pylori-positive patients than H. pylori-negative controls; however eradication therapy had no effect on the risk of relapse; ClincialTrials.gov number, NCT00574925.

  15. Effectiveness of Cranberry Capsules to Prevent Urinary Tract Infections in Vulnerable Older Persons: A Double-Blind Randomized Placebo-Controlled Trial in Long-Term Care Facilities

    Science.gov (United States)

    Caljouw, Monique A A; van den Hout, Wilbert B; Putter, Hein; Achterberg, Wilco P; Cools, Herman J M; Gussekloo, Jacobijn

    2014-01-01

    Objectives To determine whether cranberry capsules prevent urinary tract infection (UTI) in long-term care facility (LTCF) residents. Design Double-blind randomized placebo-controlled multicenter trial. Setting Long-term care facilities (LTCFs). Participants LTCF residents (N = 928; 703 women, median age 84). Measurements Cranberry and placebo capsules were taken twice daily for 12 months. Participants were stratified according to UTI risk (risk factors included long-term catheterization, diabetes mellitus, ≥1 UTI in preceding year). Main outcomes were incidence of UTI according to a clinical definition and a strict definition. Results In participants with high UTI risk at baseline (n = 516), the incidence of clinically defined UTI was lower with cranberry capsules than with placebo (62.8 vs 84.8 per 100 person-years at risk, P = .04); the treatment effect was 0.74 (95% confidence interval (CI) = 0.57–0.97). For the strict definition, the treatment effect was 1.02 (95% CI = 0.68–1.55). No difference in UTI incidence between cranberry and placebo was found in participants with low UTI risk (n = 412). Conclusion In LTCF residents with high UTI risk at baseline, taking cranberry capsules twice daily reduces the incidence of clinically defined UTI, although it does not reduce the incidence of strictly defined UTI. No difference in incidence of UTI was found in residents with low UTI risk. PMID:25180378

  16. Humoral response to blastospores and mycelium in mice injected with different doses of Candida albicans.

    Science.gov (United States)

    Mesón, O E; Valdez, J C; de Alderete, N G; Sirena, A; Perdigón, G

    1992-01-01

    An indirect immunofluorescence assay was carry out to determine the IgM and IgG antibody responses to yeast and mycelial forms of Candida albicans in mice injected with a 5 x 5(5) and 5 x 10(7) live cells suspensions. Prior adsorption of the serum samples with heat-killed blastospores enabled us to follow the specific antimycelial response which were detected considerably later than expected. Slow level of antibodies were obtained within an infection of 5 x 10(5) cell for both antibody classes and for yeast and mycelial forms. When a 5 x 10(7) cell dose was used for inoculation, maximum titers of antibodies to blastospores and mycelium in non-adsorbed sera appeared almost simultaneously (days 15 and 13, respectively). When serum samples from mice infected with the same dose were previously adsorbed with blastospores, the antimycelium antibodies for both types of Igs, were detected delayed during the infection course. In this case the higher titer for IgG appeared on day 33 and on day 23 for IgM. We suggest that the high titer obtained with the blastospore forms for the 5 x 10(7) cell dose may be due to a major immunogenicity of this forms, for to induce an immune response in the host, or that the delay in the antimycelium antibodies detection could be due to that a blastospore form is the predominant in the infection early stages. Implications of this fact for pathogenesis are discussed.

  17. Assessing the advantage of morphological changes in Candida albicans: a game theoretical study

    Directory of Open Access Journals (Sweden)

    Katarzyna M Tyc

    2014-02-01

    Full Text Available A range of attributes determines the virulence of human pathogens. During interactions with their hosts, pathogenic microbes often undergo transitions between distinct stages, and the ability to switch between these can be directly related to the disease process. Understanding the mechanisms and dynamics of these transitions is a key factor in understanding and combating infectious diseases. The human fungal pathogen Candida albicans exhibits different morphotypes at different stages during the course of infection (candidiasis. For example, hyphae are considered to be the invasive form, which causes tissue damage, while yeast cells are predominant in the commensal stage. Here, we described interactions of C. albicans with its human host in a game theoretic model. In the game, players are fungal cells. Each fungal cell can adopt one of the two strategies: to exist as a yeast or hyphal cell. We characterized the ranges of model parameters in which the coexistence of both yeast and hyphal forms is plausible. Stability analysis of the system showed that, in theory, a reduced ability of the host to specifically recognize yeast and hyphal cells can result in bi-stability of the microbial populations’ profile. Inspired by the model analysis we reasoned that the types of microbial interactions can change during invasive candidiasis. We found that positive cooperation among fungal cells occurs in mild infections and an enhanced tendency to invade the host is associated with negative cooperation. The model can easily be extended to multi-player systems with direct application to identifying individuals that enhance either positive or negative cooperation. Results of the modelling approach have potential application in developing treatment strategies.

  18. Assessing the advantage of morphological changes in Candida albicans: a game theoretical study

    Science.gov (United States)

    Tyc, Katarzyna M.; Kühn, Clemens; Wilson, Duncan; Klipp, Edda

    2014-01-01

    A range of attributes determines the virulence of human pathogens. During interactions with their hosts, pathogenic microbes often undergo transitions between distinct stages, and the ability to switch between these can be directly related to the disease process. Understanding the mechanisms and dynamics of these transitions is a key factor in understanding and combating infectious diseases. The human fungal pathogen Candida albicans exhibits different morphotypes at different stages during the course of infection (candidiasis). For example, hyphae are considered to be the invasive form, which causes tissue damage, while yeast cells are predominant in the commensal stage. Here, we described interactions of C. albicans with its human host in a game theoretic model. In the game, players are fungal cells. Each fungal cell can adopt one of the two strategies: to exist as a yeast or hyphal cell. We characterized the ranges of model parameters in which the coexistence of both yeast and hyphal forms is plausible. Stability analysis of the system showed that, in theory, a reduced ability of the host to specifically recognize yeast and hyphal cells can result in bi-stability of the microbial populations' profile. Inspired by the model analysis we reasoned that the types of microbial interactions can change during invasive candidiasis. We found that positive cooperation among fungal cells occurs in mild infections and an enhanced tendency to invade the host is associated with negative cooperation. The model can easily be extended to multi-player systems with direct application to identifying individuals that enhance either positive or negative cooperation. Results of the modeling approach have potential application in developing treatment strategies. PMID:24567730

  19. Bmh1p (14-3-3) mediates pathways associated with virulence in Candida albicans.

    Science.gov (United States)

    Kelly, Michelle N; Johnston, Douglas A; Peel, Bethany A; Morgan, Timothy W; Palmer, Glen E; Sturtevant, Joy E

    2009-05-01

    The ability of the pathogenic fungus Candida albicans to cause disease requires rapid adaptation to changes in the host environment and to an evolving host immune response. The identification of 'virulence factors' using in vitro characterization of mutant strains has traditionally relied on a common set of phenotypic and biochemical assays (most often performed at 30 degrees C) and the subsequent correlation with their corresponding virulence in mouse models of disease. Utilizing a panel of isogenic mutants for the multifunctional signal-modulating 14-3-3 protein (Bmh1p), we have found that specific mutations affect a variety of different pathways currently associated with virulence, including those involved with the formation of filaments, as well as interaction with host immune cells. Surprisingly, our studies revealed that deficiencies in many of these pathways do not always correlate with virulence in a mouse model of disseminated infection. Mutations within the binding pocket of Bmh1p that affect the ability of the protein to efficiently bind ligand had varying effects on the results of a number of in vitro and in vivo assays. The capability, in vitro, to filament in embedment conditions, and to filament and form chlamydospores under microaerophilic conditions on cornmeal agar, does not correlate with virulence. It is likely that only a subset of hyphal signalling pathways is actually required for the establishment of infection in the disseminated mouse model. Most importantly, our results suggest that the delayed onset of log-phase [corrected] growth in vitro at 37 degrees C, and not at 30 degrees C, results in an inability of these mutants to rapidly adjust to environmental changes in vivo and may be responsible for their increased clearance and reduced virulence. It is critical, therefore, that future in vitro studies of putative virulence factors in C. albicans include careful characterization at physiological temperatures.

  20. Non-albicans Candida Vulvovaginitis: Treatment Experience at a Tertiary Care Vaginitis Center.

    Science.gov (United States)

    Powell, Anna M; Gracely, Edward; Nyirjesy, Paul

    2016-01-01

    The aims of this study are to analyze a cohort of women with vulvovaginal symptoms and positive cultures for non-albicans Candida (NAC) to determine whether yeast was responsible for their symptoms and to evaluate the mycological effectiveness of various regimens. This observational study was performed from retrospective chart review of patients with positive NAC cultures between April 1, 2008, and January 31, 2011, at a tertiary care vaginitis center. Patient intake demographics were entered into a database. Follow-up visits were analyzed for data about patient treatments and outcomes. Patients were considered a clinical cure if their symptoms were significantly improved and mycologic cure (MC) if later yeast cultures were negative. If clinical symptoms improved at the same time as MC, the isolate was considered the proximate cause for the symptoms. One hundred eight patients meeting entry criteria were analyzed. Boric acid was effective at obtaining MC in 32 (78%) of 41 patients with C. glabrata, 3 of 3 patients with C. tropicalis, and 3 of 3 patients with C. lusitaniae. Fluconazole was effective as initial treatment for 3 (60%) of 5 patients with C. glabrata and 13 (81%) of 16 patients with C. parapsilosis. In 52.7% of C. glabrata, 66.7% of C. parapsilosis, and 57.1% of C. tropicalis cases, effective antifungal therapy led to symptom improvement. In a tertiary care vaginitis center, NAC, when isolated on culture, caused clinically significant infections in approximately half of symptomatic patients. A majority of infections can be effectively treated with boric acid or fluconazole regardless of the non-albicans Candida species.

  1. Genomic and Phenotypic Variation in Morphogenetic Networks of Two Candida albicans Isolates Subtends Their Different Pathogenic Potential

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    Duccio Cavalieri

    2018-01-01

    Full Text Available The transition from commensalism to pathogenicity of Candida albicans reflects both the host inability to mount specific immune responses and the microorganism’s dimorphic switch efficiency. In this study, we used whole genome sequencing and microarray analysis to investigate the genomic determinants of the phenotypic changes observed in two C. albicans clinical isolates (YL1 and YQ2. In vitro experiments employing epithelial, microglial, and peripheral blood mononuclear cells were thus used to evaluate C. albicans isolates interaction with first line host defenses, measuring adhesion, susceptibility to phagocytosis, and induction of secretory responses. Moreover, a murine model of peritoneal infection was used to compare the in vivo pathogenic potential of the two isolates. Genome sequence and gene expression analysis of C. albicans YL1 and YQ2 showed significant changes in cellular pathways involved in environmental stress response, adhesion, filamentous growth, invasiveness, and dimorphic transition. This was in accordance with the observed marked phenotypic differences in biofilm production, dimorphic switch efficiency, cell adhesion, invasion, and survival to phagocyte-mediated host defenses. The mutations in key regulators of the hyphal growth pathway in the more virulent strain corresponded to an overall greater number of budding yeast cells released. Compared to YQ2, YL1 consistently showed enhanced pathogenic potential, since in vitro, it was less susceptible to ingestion by phagocytic cells and more efficient in invading epithelial cells, while in vivo YL1 was more effective than YQ2 in recruiting inflammatory cells, eliciting IL-1β response and eluding phagocytic cells. Overall, these results indicate an unexpected isolate-specific variation in pathways important for host invasion and colonization, showing how the genetic background of C. albicans may greatly affect its behavior both in vitro and in vivo. Based on this approach, we

  2. Probiotic Bacteria Alter Pattern-Recognition Receptor Expression and Cytokine Profile in a Human Macrophage Model Challenged with Candida albicans and Lipopolysaccharide

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    Victor H. Matsubara

    2017-11-01

    Full Text Available Probiotics are live microorganisms that confer benefits to the host health. The infection rate of potentially pathogenic organisms such as Candida albicans, the most common agent associated with mucosal candidiasis, can be reduced by probiotics. However, the mechanisms by which the probiotics interfere with the immune system are largely unknown. We evaluated the effect of probiotic bacteria on C. albicans challenged human macrophages. Macrophages were pretreated with lactobacilli alone (Lactobacillus rhamnosus LR32, Lactobacillus casei L324m, or Lactobacillus acidophilus NCFM or associated with Escherichia coli lipopolysaccharide (LPS, followed by the challenge with C. albicans or LPS in a co-culture assay. The expression of pattern-recognition receptors genes (CLE7A, TLR2, and TLR4 was determined by RT-qPCR, and dectin-1 reduced levels were confirmed by flow cytometry. The cytokine profile was determined by ELISA using the macrophage cell supernatant. Overall probiotic lactobacilli down-regulated the transcription of CLEC7A (p < 0.05, resulting in the decreased expression of dectin-1 on probiotic pretreated macrophages. The tested Lactobacillus species down-regulated TLR4, and increased TLR2 mRNA levels in macrophages challenged with C. albicans. The cytokines profile of macrophages challenged with C. albicans or LPS were altered by the probiotics, which generally led to increased levels of IL-10 and IL-1β, and reduction of IL-12 production by macrophages (p < 0.05. Our data suggest that probiotic lactobacilli impair the recognition of PAMPs by macrophages, and alter the production of pro/anti-inflammatory cytokines, thus modulating inflammation.

  3. ERG2 and ERG24 Are Required for Normal Vacuolar Physiology as Well as Candida albicans Pathogenicity in a Murine Model of Disseminated but Not Vaginal Candidiasis.

    Science.gov (United States)

    Luna-Tapia, Arturo; Peters, Brian M; Eberle, Karen E; Kerns, Morgan E; Foster, Timothy P; Marrero, Luis; Noverr, Mairi C; Fidel, Paul L; Palmer, Glen E

    2015-10-01

    Several important classes of antifungal agents, including the azoles, act by blocking ergosterol biosynthesis. It was recently reported that the azoles cause massive disruption of the fungal vacuole in the prevalent human pathogen Candida albicans. This is significant because normal vacuolar function is required to support C. albicans pathogenicity. This study examined the impact of the morpholine antifungals, which inhibit later steps of ergosterol biosynthesis, on C. albicans vacuolar integrity. It was found that overexpression of either the ERG2 or ERG24 gene, encoding C-8 sterol isomerase or C-14 sterol reductase, respectively, suppressed C. albicans sensitivity to the morpholines. In addition, both erg2Δ/Δ and erg24Δ/Δ mutants were hypersensitive to the morpholines. These data are consistent with the antifungal activity of the morpholines depending upon the simultaneous inhibition of both Erg2p and Erg24p. The vacuoles within both erg2Δ/Δ and erg24Δ/Δ C. albicans strains exhibited an aberrant morphology and accumulated large quantities of the weak base quinacrine, indicating enhanced vacuolar acidification compared with that of control strains. Both erg mutants exhibited significant defects in polarized hyphal growth and were avirulent in a mouse model of disseminated candidiasis. Surprisingly, in a mouse model of vaginal candidiasis, both mutants colonized mice at high levels and induced a pathogenic response similar to that with the controls. Thus, while targeting Erg2p or Erg24p alone could provide a potentially efficacious therapy for disseminated candidiasis, it may not be an effective strategy to treat vaginal infections. The potential value of drugs targeting these enzymes as adjunctive therapies is discussed. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  4. Low virulent oral Candida albicans strains isolated from smokers.

    Science.gov (United States)

    de Azevedo Izidoro, Ana Claudia Santos; Semprebom, Andressa Marafon; Baboni, Fernanda Brasil; Rosa, Rosimeire Takaki; Machado, Maria Angela Naval; Samaranayake, Lakshman Perera; Rosa, Edvaldo Antonio Ribeiro

    2012-02-01

    It is widely accepted that tabagism is a predisposing factor to oral candidosis and cumulate data suggest that cigarette compounds may increase candidal virulence. To verify if enhanced virulence occurs in Candida albicans from chronic smokers, a cohort of 42 non-smokers and other of 58 smokers (all with excellent oral conditions and without signs of candidosis) were swabbed on tong dorsum and jugal mucosa. Results showed that oral candidal loads do not differ between smoker and non-smokers. Activities of secreted aspartyl-protease (Sap), phospholipase, chondroitinase, esterase-lipase, and haemolysin secretions were screened for thirty-two C. albicans isolates. There were detected significant increments in phospholipasic and chondroitinasic activities in isolates from non-smokers. For other virulence factors, no differences between both cohorts were achieved. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Genoma de Candida albicans y resistencia a las drogas

    OpenAIRE

    Cruz Quintana, Sandra; Díaz Sjostrom, Pedro; Mazón Baldeón, Gloria; Arias Socarrás, Dunier; Calderón Paz, María; Herrera Molina, Angélica

    2017-01-01

    Resumen Candida albicans es un importante patógeno fúngico en los humanos tanto por su importancia clínica como por su uso como un modelo experimental para la investigación científica. La comprensión de la biología de este patógeno es un requisito importante para la identificación de nuevas dianas de medicamentos para la terapia antifúngica. En esta revisión nos proponemos profundizar en las características del genoma de Candida albicans, su relación con la virulencia y cómo influye en la res...

  6. Genoma de Candida albicans y resistencia a las drogas

    OpenAIRE

    Sandra Cruz Quintana; Pedro Díaz Sjostrom; Gloria Mazón Baldeón; Dunier Arias Socarrás; María Calderón Paz; Angélica Herrera Molina

    2017-01-01

    Candida albicans es un importante patógeno fúngico en los humanos tanto por su importan - cia clínica como por su uso como un modelo experimental para la investigación científica. La comprensión de la biología de este patógeno es un requisito importante para la identificación de nuevas dianas de medicamentos para la terapia antifúngica. En esta revisión nos proponemos profundizar en las características del genoma de Candida albicans, su relación con la virulen - cia y cómo influye en la re...

  7. Deoxyribonucleic acid-deficient strains of Candida albicans.

    Science.gov (United States)

    Olaiya, A F; Steed, J R; Sogin, S J

    1980-03-01

    We analyzed a series of germ tube-negative variants isolated from Candida albicans 3153A for deoxyribonucleic acid content. As analyzed by flow microfluorometry, the deoxyribonucleic acid level in these variant strains was 50% of that of the parental strain and equivalent to that of haploid Saccharomyces cerevisiae. This finding was confirmed by comparison of survival rates when exposed to the mutagens ultraviolet light, ethyl methane sulfonate, and methyl methane sulfonate. The diameter of the variant cells as compared to the diameter of the parental 3153A strain showed a relationship similar to that of the diameters of haploid versus diploid S. cerevisiae. These results indicate that those strains may be representative of the imperfect stage of C. albicans.

  8. Candida species isolated from different body sites and their antifungal susceptibility pattern: Cross-analysis of Candida albicans and Candida glabrata biofilms.

    Science.gov (United States)

    Cataldi, Valentina; Di Campli, Emanuela; Fazii, Paolo; Traini, Tonino; Cellini, Luigina; Di Giulio, Mara

    2017-08-01

    Candida species are regular commensal in humans, but-especially in immunocompromised patients-they represent opportunistic pathogens giving rise to systemic infection. The aim of the present work was to isolate and characterize for their antifungal profile Candida species from different body sites and to analyze the biofilms produced by C. albicans and C. glabrata isolates. Eighty-one strains of Candida species from 77 patients were identified. Epidemiological study showed that the most isolated species were C. albicans (44), C. glabrata (13) and C. parapsilosis (13) mainly from Hematology, Infectious Diseases, Medicine, Neonatology and Oncology Divisions, the majority of the biological samples were swabs (44) and blood cultures (16). The analysis of the biofilm formation was performed at 24 and 48-hours comparing resistant and susceptible strains of C. albicans to resistant and susceptible strains of C. glabrata. Candida albicans has a greater ability to form biofilm compared to C. glabrata, both in the susceptible and resistant strains reaching maturity after 24 hours with a complex structure composed of blastospores, pseudohyphae, and hyphae embedded in a matrix. On the contrary, C. glabrata biofilm was composed exclusively of blastospores that in the resistant strain, after 24 hours, were organized in a compact multilayer different to the discontinuous structure observed in the susceptible analyzed strains. In conclusion, the increasing of the incidence of Candida species infection together with their emerging drug resistance also related to the biofilm forming capability underline the need to monitor their distribution and susceptibility patterns for improving the surveillance and for a correct management of the infection. © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. Candida albicans in patients with oronasal communication and obturator prostheses

    OpenAIRE

    MATTOS, Beatriz Silva Câmara; SOUSA, Andréa Alves de; MAGALHÃES, Marina Helena C. G. de; ANDRÉ, Marcia; BRITO E DIAS, Reinaldo

    2009-01-01

    Patients using obturator prostheses often present denture-induced stomatitis. In order to detect the presence of oral Candida albicans in patients with oronasal communications and to evaluate the effectiveness of a topical antifungal treatment, cytological smears obtained from the buccal and palatal mucosa of 10 adult patients, and from the nasal acrylic surface of their obturator prostheses were examined. A therapeutic protocol comprising the use of oral nystatin (Mycostatin®) and prosthesis...

  10. Limonene inhibits Candida albicans growth by inducing apoptosis.

    Science.gov (United States)

    Thakre, Archana; Zore, Gajanan; Kodgire, Santosh; Kazi, Rubina; Mulange, Shradha; Patil, Rajendra; Shelar, Amruta; Santhakumari, Bayitigeri; Kulkarni, Mahesh; Kharat, Kiran; Karuppayil, Sankunny Mohan

    2018-07-01

    Anti-Candida potential of limonene was evaluated against planktonic growth, biofilm (adhesion, development and maturation) and morphogenesis of Candida albicans in this study. Limonene is a major constituent of citrus oil and most frequently used terpene in food and beverage industry due to its pleasant fragrance, nontoxic, and is generally recognized as safe (GRAS) flavoring agent as well as treatment option in many gastrointestinal diseases.Limonene exhibited excellent anti-Candida activity and was equally effective against planktonic growth of C. albicans isolates differentially susceptible to FLC (N = 35). Limonene inhibited morphogenesis significantly at low concentration. However, it showed stage dependent activity against biofilm formation, that is, it was more effective against adhesion followed by development and maturation. Limonene also exhibited excellent synergy with FLC against planktonic and biofilm growth. SWATH-MS analysis led to identification of limonene responsive proteins that provided molecular insight of its anti-Candida activity. Proteomic analysis revealed upregulation of proteins involved in cell wall glucan synthesis (Kre6); oxidative stress (Rhr2, Adh7 and Ebp1); DNA damage stress (Mbf1 and Npl3); nucleolar stress (Rpl11, Rpl7, Rpl29, Rpl15) and down regulation of cytoskeleton organization (Crn1, Pin3, Cct8, Rbl2), and so forth, in response to limonene. Limonene mediated down regulation of Tps3 indicates activation of caspase (CaMca1) and induction of apoptosis in C. albicans. These results suggest that limonene inhibits C. albicans growth by cell wall/membrane damage induced oxidative stress that leads to DNA damage resulting into modulation of cell cycle and induction of apoptosis through nucleolar stress and metacaspase dependent pathway.

  11. Competitive Fitness of Fluconazole-Resistant Clinical Candida albicans Strains.

    Science.gov (United States)

    Popp, Christina; Hampe, Irene A I; Hertlein, Tobias; Ohlsen, Knut; Rogers, P David; Morschhäuser, Joachim

    2017-07-01

    The pathogenic yeast Candida albicans can develop resistance to the widely used antifungal agent fluconazole, which inhibits ergosterol biosynthesis. Resistance is often caused by gain-of-function mutations in the transcription factors Mrr1 and Tac1, which result in constitutive overexpression of multidrug efflux pumps, and Upc2, which result in constitutive overexpression of ergosterol biosynthesis genes. However, the deregulated gene expression that is caused by hyperactive forms of these transcription factors also reduces the fitness of the cells in the absence of the drug. To investigate whether fluconazole-resistant clinical C. albicans isolates have overcome the fitness costs of drug resistance, we assessed the relative fitness of C. albicans isolates containing resistance mutations in these transcription factors in competition with matched drug-susceptible isolates from the same patients. Most of the fluconazole-resistant isolates were outcompeted by the corresponding drug-susceptible isolates when grown in rich medium without fluconazole. On the other hand, some resistant isolates with gain-of-function mutations in MRR1 did not exhibit reduced fitness under these conditions. In a mouse model of disseminated candidiasis, three out of four tested fluconazole-resistant clinical isolates did not exhibit a significant fitness defect. However, all four fluconazole-resistant isolates were outcompeted by the matched susceptible isolates in a mouse model of gastrointestinal colonization, demonstrating that the effects of drug resistance on in vivo fitness depend on the host niche. Collectively, our results indicate that the fitness costs of drug resistance in C. albicans are not easily remediated, especially when proper control of gene expression is required for successful adaptation to life within a mammalian host. Copyright © 2017 American Society for Microbiology.

  12. ANTAGONISTIC EFFECT OF EDIBLE MUSHROOM EXTRACT ON CANDIDA ALBICANS GROWTH

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    Paccola Edneia A. de Souza

    2001-01-01

    Full Text Available Five species of edible mushrooms, Lentinula edodes, Pleurotus ostreatus, Pholiota nameko, Macrolepiota bonaerensis and Agaricus blazei, were tested for their potential to inhibit the in vitro growth of the pathogenic yeast Candida albicans. Only L. edodes had a fungistatic effect on this human pathogen. The inhibitory compound was produced intra and extracellularly in submersed L. edodes culture, and was also present in fresh and dehydrated mushroom basidiocarps. The fungistatic compound was heat sensitive and lost activity after 72 hours.

  13. Deoxyribonucleic acid-deficient strains of Candida albicans.

    OpenAIRE

    Olaiya, A F; Steed, J R; Sogin, S J

    1980-01-01

    We analyzed a series of germ tube-negative variants isolated from Candida albicans 3153A for deoxyribonucleic acid content. As analyzed by flow microfluorometry, the deoxyribonucleic acid level in these variant strains was 50% of that of the parental strain and equivalent to that of haploid Saccharomyces cerevisiae. This finding was confirmed by comparison of survival rates when exposed to the mutagens ultraviolet light, ethyl methane sulfonate, and methyl methane sulfonate. The diameter of t...

  14. Studies on effect of Microbial Iron Chelators on Candida Albican

    International Nuclear Information System (INIS)

    Rehmani, Fouzia S.; Milicent, S.; Zaheer-Uddin

    2005-01-01

    Iron is an essential for the life of all microbe cells. It generally exists in the oxidized form Fe(III). Even under anaerobic reducing condition the metal appear to be taken up as Fe(III). Thus free-living microorganisms require specific and effective ferric ion transport system to cope with low availability of the metal. In iron deficient environment they produce a low molecular weight specific chelators called siderphores or microbial iron chelators. Siderphores compete for limited supplied of iron. These compounds came out of the cell but can not re-enter without iron due to high affinity of these siderphores often have more than one catechol/hydroxamate functions and are multidentate (usually hexadentate ligands). The aim of the present research is to check the effect of iron chelators, namely gallic acid and salisyl hydroxamate on the growth of Candida albican in vitro. C. albican is the opportunistic paltogen present as the normal flora inside human body. In vivo the growth of C. albican is distributed by the use of antibiotics and immuno suppressers. In cases of iron over-dosage in human being, the patients are treated with certain a-iron chelators. Hence an attempt is made to notice the effect that might be inhibition or enhancement of the organism in vitro. (author)

  15. Anti-Candida albicans biofilm effect of novel heterocyclic compounds.

    Science.gov (United States)

    Kagan, Sarah; Jabbour, Adel; Sionov, Edward; Alquntar, Abed A; Steinberg, Doron; Srebnik, Morris; Nir-Paz, Ran; Weiss, Aryeh; Polacheck, Itzhack

    2014-02-01

    The aims of this study were to develop new anti-biofilm drugs, examine their activity against Candida albicans biofilm and investigate their structure-activity relationship and mechanism of action. A series of thiazolidinedione and succinimide derivatives were synthesized and their ability to inhibit C. albicans biofilm formation and destroy pre-formed biofilm was tested. The biofilms' structure, metabolic activity and viability were determined by XTT assay and propidium iodide and SYTO 9 live/dead stains combined with confocal microscopic analysis. The effect of the most active compounds on cell morphology, sterol distribution and cell wall morphology and composition was then determined by specific fluorescent stains and transmission electron microscopy. Most of the compounds were active at sub-MICs. Elongation of the aliphatic side chain resulted in reduced anti-biofilm activity and the sulphur atom contributed to biofilm killing, indicating a structure-activity relationship. The compounds differed in their effects on biofilm viability, yeast-to-hyphal form transition, hyphal morphology, cell wall morphology and composition, and sterol distribution. The most effective anti-biofilm compounds were the thiazolidinedione S8H and the succinimide NA8. We developed novel anti-biofilm agents that both inhibited and destroyed C. albicans biofilm. With some further development, these agents might be suitable for therapeutic purposes.

  16. A randomized, double-blind trial comparing combinations of nevirapine, didanosine, and zidovudine for HIV-infected patients: the INCAS Trial. Italy, The Netherlands, Canada and Australia Study.

    Science.gov (United States)

    Montaner, J S; Reiss, P; Cooper, D; Vella, S; Harris, M; Conway, B; Wainberg, M A; Smith, D; Robinson, P; Hall, D; Myers, M; Lange, J M

    1998-03-25

    Current guidelines recommend that individuals infected with the human immunodeficiency virus type 1 (HIV-1) be treated using combinations of antiretroviral agents to achieve sustained suppression of viral replication as measured by the plasma HIV-1 RNA assay, in the hopes of achieving prolonged remission of the disease. However, until recently, many drug combinations have not led to sustained suppression of HIV-1 RNA. To compare the virologic effects of various combinations of nevirapine, didanosine, and zidovudine. Double-blind, controlled, randomized trial. University-affiliated ambulatory research clinics in Italy, the Netherlands, Canada and Australia (INCAS). Antiretroviral therapy-naive adults free of the acquired immunodeficiency syndrome with CD4 cell counts between 0.20 and 0.60x10(9)/L (200-600/microL). Patients received zidovudine plus nevirapine (plus didanosine placebo), zidovudine plus didanosine (plus nevirapine placebo), or zidovudine plus didanosine plus nevirapine. Plasma HIV-1 RNA. Of the 153 enrolled patients, 151 were evaluable. At week 8, plasma HIV-1 RNA levels had decreased by log 2.18, 1.55, and 0.90 in the triple drug therapy, zidovudine plus didanosine, and zidovudine plus nevirapine groups, respectively (P<.05). The proportions of patients with plasma HIV-1 RNA levels below 20 copies per milliliter at week 52 were 51%, 12%, and 0% in the triple drug therapy, zidovudine plus didanosine, and zidovudine plus nevirapine groups, respectively (P<.001). Viral amplification was attempted in 59 patients at 6 months. Viral isolation was unsuccessful in 19 (79%) of 24, 10 (53%) of 19, and 5 (31%) of 16 patients in the triple drug therapy, zidovudine plus didanosine, and zidovudine plus nevirapine groups, respectively. Among patients from whom virus could be amplified, resistance to nevirapine was found in all 11 patients receiving zidovudine plus nevirapine and in all 5 patients receiving triple drug therapy. Rates of disease progression or death

  17. The MARVEL domain protein Nce102 regulates actin organization and invasive growth of Candida albicans.

    Science.gov (United States)

    Douglas, Lois M; Wang, Hong X; Konopka, James B

    2013-11-26

    Invasive growth of the fungal pathogen Candida albicans into tissues promotes disseminated infections in humans. The plasma membrane is essential for pathogenesis because this important barrier mediates morphogenesis and invasive growth, as well as secretion of virulence factors, cell wall synthesis, nutrient import, and other processes. Previous studies showed that the Sur7 tetraspan protein that localizes to MCC (membrane compartment occupied by Can1)/eisosome subdomains of the plasma membrane regulates a broad range of key functions, including cell wall synthesis, morphogenesis, and resistance to copper. Therefore, a distinct tetraspan protein found in MCC/eisosomes, Nce102, was investigated. Nce102 belongs to the MARVEL domain protein family, which is implicated in regulating membrane structure and function. Deletion of NCE102 did not cause the broad defects seen in sur7Δ cells. Instead, the nce102Δ mutant displayed a unique phenotype in that it was defective in forming hyphae and invading low concentrations of agar but could invade well in higher agar concentrations. This phenotype was likely due to a defect in actin organization that was observed by phalloidin staining. In support of this, the invasive growth defect of a bni1Δ mutant that mislocalizes actin due to lack of the Bni1 formin was also reversed at high agar concentrations. This suggests that a denser matrix provides a signal that compensates for the actin defects. The nce102Δ mutant displayed decreased virulence and formed abnormal hyphae in mice. These studies identify novel ways that Nce102 and the physical environment surrounding C. albicans regulate morphogenesis and pathogenesis. The plasma membrane promotes virulence of the human fungal pathogen Candida albicans by acting as a protective barrier around the cell and mediating dynamic activities, such as morphogenesis, cell wall synthesis, secretion of virulence factors, and nutrient uptake. To better understand how the plasma membrane

  18. Oral prenylation inhibition with lonafarnib in chronic hepatitis D infection: a proof-of-concept randomised, double-blind, placebo-controlled phase 2A trial

    Science.gov (United States)

    Koh, Christopher; Canini, Laetitia; Dahari, Harel; Zhao, Xiongce; Uprichard, Susan L; Haynes-Williams, Vanessa; Winters, Mark A; Subramanya, Gitanjali; Cooper, Stewart L; Pinto, Peter; Wolff, Erin F; Bishop, Rachel; Han, Ma Ai Thanda; Cotler, Scott J; Kleiner, David E; Keskin, Onur; Idilman, Ramazan; Yurdaydin, Cihan; Glenn, Jeffrey S; Heller, Theo

    2015-01-01

    Summary Background Therapies for chronic hepatitis delta virus (HDV) infection are unsatisfactory. Prenylation is essential for HDV and inhibition abrogates HDV production in experimental models. In a proof-of-concept study, we aimed to assess the effect on HDV RNA levels, safety, and tolerability of the prenylation inhibitor lonafarnib in patients with chronic delta hepatitis. Methods In this phase 2A double-blind, randomised, placebo-controlled study, patients aged 18 years or older with chronic HDV infection were randomly assigned (3:1 in group 1 and 2:1 in group 2) to receive lonafarnib 100 mg (group 1) or lonafarnib 200 mg (group 2) twice daily for 28 days with 6 months’ follow-up. Participants were randomised by random-number tables blocked in groups of four without stratification. Both groups enrolled six treatment participants and two placebo participants. Group 1 placebo patients received open-label lonafarnib as group 2 participants. The primary therapeutic endpoint was a decrease in HDV RNA viral titre in serum and the primary safety endpoint was the ability to tolerate the drug at the prescribed dose for the full 4-week duration, defined as drug discontinuation due to intolerance or grade 3/4 adverse events. This trial is registered with ClinicalTrials.gov, number NCT01495585. Findings Between Jan 19, 2012, and April 28, 2014, 14 patients were enrolled, of whom eight were assigned to group 1 and six were assigned to group 2. At day 28, compared with placebo, mean log HDV RNA declines from baseline were −0.73 log IU/mL in group 1 (95% CI 0.17–1.31; p=0.03) and −1.54 log IU/mL in group 2 (1.21–1.93; p<0.0001). Lonafarnib serum concentrations correlated with HDV RNA change (r2=0.78, p<0.0001). Model fits show that hepatitis B surface antigen (HBsAg) remained stable after a short pharmacological delay (0.75 days [SE 0.24]), lonafarnib effectiveness in blocking HDV production was greater in group 2 than in group 1 (0.952 [SE 0.06] vs 0.739 [0

  19. SDS-Page and numerical analysis of Candida albicans from human oral cavity and other anatomical sites Eletroforese de proteínas totais e análise numérica de Candida albicans isolada da cavidade oral e outros sítios anatômicos de humanos

    Directory of Open Access Journals (Sweden)

    Cristina Crespo Rodrigues

    2004-06-01

    Full Text Available The aim of the present research was to evaluate the protein polymorphism degrees among forty-eight C. albicans isolates from fourteen anatomical sites of clinical patients by polyacrylamide gel electrophoresis (SDS-PAGE and numerical analyzes, in order to identify subspecies and their similarities in some infectious niches. Cell cultures were grown in YEPD medium, collected by centrifugation, and washed in cold saline solution. The whole-cell proteins were extracted by cell disruption using glass beads and submitted to SDS-PAGE technique. After electrophoresis, the protein bands were stained with coomassie-blue and analyzed by statistics package NTSYS-pc version 1.70 software. Similarity matrixes and dendrograms were generated by application of similarity coefficient of simple matching and UPGMA algorithm, respectively. The results obtained showed several C. albicans subtypes and their similarity degrees (80% to 100%. Such data showed that same patients may be infected by two or more C. albicans subtypes in certain anatomical sites (i.e. only in oral cavity of immunocompromised patients, blood, or tracheal secretion, or yet, two or more patients can be infected in identical anatomical sites (i.e. bronchial washing, urine, oral cavity, tracheal secretion, vaginal secretion, and healthy saliva with a same C. albicans subtype. However, two or more patients also can show infections in corresponding sites (i.e. oral cavity of immunocompromised patients, blood, oropharyngeal secretion, oral cavity, tracheal secretion, vaginal secretion, and healthy saliva by different C. albicans subtypes. Besides, two or more patients also can be infected with identical or different C. albicans subtypes in different anatomical sites (i.e.1. identical subtypes in vaginal secretion, tracheal secretion, and urine; abdominal secretion and spittle; drainage and oral cavity; catheter and healthy saliva - i.e.2. subtypes different in bronchial washing, oropharyngeal

  20. Antifungal Effect of Lavender Essential Oil (Lavandula angustifolia and Clotrimazole on Candida albicans: An In Vitro Study

    Directory of Open Access Journals (Sweden)

    Fereshteh Behmanesh

    2015-01-01

    Full Text Available Background. The treatment of candidiasis infections is an important problem in the health care system. This study aimed to investigate the in vitro effect of lavender essential oil and clotrimazole on isolated C. albicans from vaginal candidiasis. Materials and Methods. In this clinical trial, C. albicans isolated from the vaginal discharge samples was obtained. Results. The pairwise comparison showed that lavender and clotrimazole had a significant difference; this difference in the lavender group was lower than clotrimazole. But, after 48 hours, there was no difference seen between groups. There was a significant difference between clotrimazole and DMSO groups. Comparing the changes between groups based on the same dilution, at 24 h and 48 h in clotrimazole group, showed a significant difference two times in the fungal cell count that its average during 48 h was less than 24 h. A significant difference was observed between the two periods in lavender group, only at the dilutions of 1/20 and 1/80. The average fungal cell count after 48 h was also lower in lavender group. Conclusions. Given that the lavender has antifungal activity, this can be used as an antifungal agent. However, more clinical studies are necessary to validate its use in candida infection.

  1. Adaptation of Candida albicans to environmental pH induces cell wall remodelling and enhances innate immune recognition.

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    Sarah L Sherrington

    2017-05-01

    Full Text Available Candida albicans is able to proliferate in environments that vary dramatically in ambient pH, a trait required for colonising niches such as the stomach, vaginal mucosal and the GI tract. Here we show that growth in acidic environments involves cell wall remodelling which results in enhanced chitin and β-glucan exposure at the cell wall periphery. Unmasking of the underlying immuno-stimulatory β-glucan in acidic environments enhanced innate immune recognition of C. albicans by macrophages and neutrophils, and induced a stronger proinflammatory cytokine response, driven through the C-type lectin-like receptor, Dectin-1. This enhanced inflammatory response resulted in significant recruitment of neutrophils in an intraperitoneal model of infection, a hallmark of symptomatic vaginal colonisation. Enhanced chitin exposure resulted from reduced expression of the cell wall chitinase Cht2, via a Bcr1-Rim101 dependent signalling cascade, while increased β-glucan exposure was regulated via a non-canonical signalling pathway. We propose that this "unmasking" of the cell wall may induce non-protective hyper activation of the immune system during growth in acidic niches, and may attribute to symptomatic vaginal infection.

  2. Adaptation of Candida albicans to environmental pH induces cell wall remodelling and enhances innate immune recognition

    Science.gov (United States)

    Sorsby, Eleanor; Mahtey, Nabeel; Brown, Ian

    2017-01-01

    Candida albicans is able to proliferate in environments that vary dramatically in ambient pH, a trait required for colonising niches such as the stomach, vaginal mucosal and the GI tract. Here we show that growth in acidic environments involves cell wall remodelling which results in enhanced chitin and β-glucan exposure at the cell wall periphery. Unmasking of the underlying immuno-stimulatory β-glucan in acidic environments enhanced innate immune recognition of C. albicans by macrophages and neutrophils, and induced a stronger proinflammatory cytokine response, driven through the C-type lectin-like receptor, Dectin-1. This enhanced inflammatory response resulted in significant recruitment of neutrophils in an intraperitoneal model of infection, a hallmark of symptomatic vaginal colonisation. Enhanced chitin exposure resulted from reduced expression of the cell wall chitinase Cht2, via a Bcr1-Rim101 dependent signalling cascade, while increased β-glucan exposure was regulated via a non-canonical signalling pathway. We propose that this “unmasking” of the cell wall may induce non-protective hyper activation of the immune system during growth in acidic niches, and may attribute to symptomatic vaginal infection. PMID:28542528

  3. Effect of Xylitol on Candida albicans resistance in serum (in vitro study

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    Ria Puspitawati

    2013-07-01

    Full Text Available Xylitol is reported to inhibit the growth of C. albicans. Objectives: Investigating serum factor role in inhibiting the growth of C. albicans and the effect of 1%, 5%, 10% xylitol on C. albicans resistance in serum in vitro. Methods: Identification of C. albicans (oral swab of candidiasis patient was conducted using CHROMAgar, confirmed by germ tube test. The cultures were serially diluted, inoculated in Saburoud Dextrose Broth (SDB contained 0% (control, 1%, 5%, or 10% xylitol, and kept for 3 or 7 days. These inoculations were then exposed to either active or inactive serum (Fetal Bovine Serum heated in 65ºC for 30 minutes for 2 hours in 37ºC. The colony forming unit (CFU of C. albicans in Saburoud Dextrose Agar (SDA were counted after 2 days. C. albicans ATCC 10231 strain was used as a comparison. One-way ANOVA with 0.05 was used. Results: After 3 days cultured in media with or without xylitol, the CFU of C. albicans exposed to active serum were significantly lower than those exposed to inactive serum (p=0.032. Although not statistically significant (p=0.689, increased concentration of xylitol lead to increased resistance of C. albicans in active serum. Only 7 day exposure of 10% xylitol resulted in significantly higher growth of C. albicans (p=0.034. No significant difference of C. albicans CFU in active or inactive serum (p=0.404. Conclusion: Serum factor has role in inhibiting C. albicans growth in vitro. Exposure of 1%, 5%, or 10% xylitol for 3 or 7 days has no significant effect on C. albicans resistance in serum.DOI: 10.14693/jdi.v16i2.98

  4. Antibiofilm and Antihyphal Activities of Cedar Leaf Essential Oil, Camphor, and Fenchone Derivatives against Candida albicans

    OpenAIRE

    Manoharan, Ranjith Kumar; Lee, Jin-Hyung; Lee, Jintae

    2017-01-01

    Candida albicans can form biofilms composed of yeast, hyphal, and pseudohyphal elements, and C. albicans cells in the hyphal stage could be a virulence factor. The present study describes the chemical composition, antibiofilm, and antihyphal activities of cedar leaf essential oil (CLEO), which was found to possess remarkable antibiofilm activity against C. albicans but not to affect its planktonic cell growth. Nineteen components were identified in CLEO by gas chromatography/mass spectrometry...

  5. Whole Saliva has a Dual Role on the Adherence of Candida albicans to Polymethylmetacrylate

    OpenAIRE

    Elguezabal, N; Maza, J.L.; Dorronsoro, S.; Pont?n, J.

    2008-01-01

    Adhesion of Candida albicans to acrylic of dental prostheses or to salivary macromolecules adsorbed on their surface is believed to be a critical event in the development of denture stomatitis. In previous studies our group has shown that adhesion of C. albicans germ tubes to polystyrene is decreased by saliva whereas C. albicans yeast cells adhesion to the same material is enhanced. The results presented in this study confirm this dual role played by whole saliva, since it decreased the adhe...

  6. Sputum Candida albicans presages FEV₁ decline and hospital-treated exacerbations in cystic fibrosis.

    LENUS (Irish Health Repository)

    Chotirmall, Sanjay H

    2010-11-01

    The role of Candida albicans in the cystic fibrosis (CF) airway is underexplored. Considered a colonizer, few question its pathogenic potential despite high isolation frequencies from sputum culture. We evaluated the frequency and identified the strongest predictors of C albicans colonization in CF. Independent associations of colonization with clinical outcomes were determined, and the longitudinal effects of C albicans acquisition on BMI and FEV₁ were evaluated.

  7. Molecular mechanisms of action of herbal antifungal alkaloid berberine, in Candida albicans.

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    Sanjiveeni Dhamgaye

    Full Text Available Candida albicans causes superficial to systemic infections in immuno-compromised individuals. The concomitant use of fungistatic drugs and the lack of cidal drugs frequently result in strains that could withstand commonly used antifungals, and display multidrug resistance (MDR. In search of novel fungicidals, in this study, we have explored a plant alkaloid berberine (BER for its antifungal potential. For this, we screened an in-house transcription factor (TF mutant library of C. albicans strains towards their susceptibility to BER. Our screen of TF mutant strains identified a heat shock factor (HSF1, which has a central role in thermal adaptation, to be most responsive to BER treatment. Interestingly, HSF1 mutant was not only highly susceptible to BER but also displayed collateral susceptibility towards drugs targeting cell wall (CW and ergosterol biosynthesis. Notably, BER treatment alone could affect the CW integrity as was evident from the growth retardation of MAP kinase and calcineurin pathway null mutant strains and transmission electron microscopy. However, unlike BER, HSF1 effect on CW appeared to be independent of MAP kinase and Calcineurin pathway genes. Additionally, unlike hsf1 null strain, BER treatment of Candida cells resulted in dysfunctional mitochondria, which was evident from its slow growth in non-fermentative carbon source and poor labeling with mitochondrial membrane potential sensitive probe. This phenotype was reinforced with an enhanced ROS levels coinciding with the up-regulated oxidative stress genes in BER-treated cells. Together, our study not only describes the molecular mechanism of BER fungicidal activity but also unravels a new role of evolutionary conserved HSF1, in MDR of Candida.

  8. Cushing's syndrome complicated by multiple opportunistic infections

    NARCIS (Netherlands)

    Bakker, R. C.; Gallas, P. R.; Romijn, J. A.; Wiersinga, W. M.

    1998-01-01

    The case history of a 56-year-old man is described who suffered from severe adrenocorticotrophic hormone (ACTH)-dependent Cushing's syndrome. The clinical course was complicated by simultaneous infections with Pneumocystis carinii, Staphylococcus aureus, Candida albicans, Aspergillus fumigatus and

  9. A novel role for the NLRC4 inflammasome in mucosal defenses against the fungal pathogen Candida albicans.

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    Jeffrey Tomalka

    2011-12-01

    Full Text Available Candida sp. are opportunistic fungal pathogens that colonize the skin and oral cavity and, when overgrown under permissive conditions, cause inflammation and disease. Previously, we identified a central role for the NLRP3 inflammasome in regulating IL-1β production and resistance to dissemination from oral infection with Candida albicans. Here we show that mucosal expression of NLRP3 and NLRC4 is induced by Candida infection, and up-regulation of these molecules is impaired in NLRP3 and NLRC4 deficient mice. Additionally, we reveal a role for the NLRC4 inflammasome in anti-fungal defenses. NLRC4 is important for control of mucosal Candida infection and impacts inflammatory cell recruitment to infected tissues, as well as protects against systemic dissemination of infection. Deficiency in either NLRC4 or NLRP3 results in severely attenuated pro-inflammatory and antimicrobial peptide responses in the oral cavity. Using bone marrow chimeric mouse models, we show that, in contrast to NLRP3 which limits the severity of infection when present in either the hematopoietic or stromal compartments, NLRC4 plays an important role in limiting mucosal candidiasis when functioning at the level of the mucosal stroma. Collectively, these studies reveal the tissue specific roles of the NLRP3 and NLRC4 inflammasome in innate immune responses against mucosal Candida infection.

  10. Polymer multilayers loaded with antifungal β-peptides kill planktonic Candida albicans and reduce formation of fungal biofilms on the surfaces of flexible catheter tubes.

    Science.gov (United States)

    Raman, Namrata; Lee, Myung-Ryul; Palecek, Sean P; Lynn, David M

    2014-10-10

    Candida albicans is the most common fungal pathogen responsible for hospital-acquired infections. Most C. albicans infections are associated with the implantation of medical devices that act as points of entry for the pathogen and as substrates for the growth of fungal biofilms that are notoriously difficult to eliminate by systemic administration of conventional antifungal agents. In this study, we report a fill-and-purge approach to the layer-by-layer fabrication of biocompatible, nanoscale 'polyelectrolyte multilayers' (PEMs) on the luminal surfaces of flexible catheters, and an investigation of this platform for the localized, intraluminal release of a cationic β-peptide-based antifungal agent. We demonstrate that polyethylene catheter tubes with luminal surfaces coated with multilayers ~700nm thick fabricated from poly-l-glutamic acid (PGA) and poly-l-lysine (PLL) can be loaded, post-fabrication, by infusion with β-peptide, and that this approach promotes extended intraluminal release of this agent (over ~4months) when incubated in physiological media. The β-peptide remained potent against intraluminal inoculation of the catheters with C. albicans and substantially reduced the formation of C. albicans biofilms on the inner surfaces of film-coated catheters. Finally, we report that these β-peptide-loaded coatings exhibit antifungal activity under conditions that simulate intermittent catheter use and microbial challenge for at least three weeks. We conclude that β-peptide-loaded PEMs offer a novel and promising approach to kill C. albicans and prevent fungal biofilm formation on surfaces, with the potential to substantially reduce the incidence of device-associated infections in indwelling catheters. β-Peptides comprise a promising new class of antifungal agents that could help address problems associated with the use of conventional antifungal agents. The versatility of the layer-by-layer approach used here thus suggests additional opportunities to

  11. PKC signaling regulates drug resistance of the fungal pathogen Candida albicans via circuitry comprised of Mkc1, calcineurin, and Hsp90.

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    Shantelle L LaFayette

    2010-08-01

    Full Text Available Fungal pathogens exploit diverse mechanisms to survive exposure to antifungal drugs. This poses concern given the limited number of clinically useful antifungals and the growing population of immunocompromised individuals vulnerable to life-threatening fungal infection. To identify molecules that abrogate resistance to the most widely deployed class of antifungals, the azoles, we conducted a screen of 1,280 pharmacologically active compounds. Three out of seven hits that abolished azole resistance of a resistant mutant of the model yeast Saccharomyces cerevisiae and a clinical isolate of the leading human fungal pathogen Candida albicans were inhibitors of protein kinase C (PKC, which regulates cell wall integrity during growth, morphogenesis, and response to cell wall stress. Pharmacological or genetic impairment of Pkc1 conferred hypersensitivity to multiple drugs that target synthesis of the key cell membrane sterol ergosterol, including azoles, allylamines, and morpholines. Pkc1 enabled survival of cell membrane stress at least in part via the mitogen activated protein kinase (MAPK cascade in both species, though through distinct downstream effectors. Strikingly, inhibition of Pkc1 phenocopied inhibition of the molecular chaperone Hsp90 or its client protein calcineurin. PKC signaling was required for calcineurin activation in response to drug exposure in S. cerevisiae. In contrast, Pkc1 and calcineurin independently regulate drug resistance via a common target in C. albicans. We identified an additional level of regulatory control in the C. albicans circuitry linking PKC signaling, Hsp90, and calcineurin as genetic reduction of Hsp90 led to depletion of the terminal MAPK, Mkc1. Deletion of C. albicans PKC1 rendered fungistatic ergosterol biosynthesis inhibitors fungicidal and attenuated virulence in a murine model of systemic candidiasis. This work establishes a new role for PKC signaling in drug resistance, novel circuitry through which

  12. Patterns of soil-transmitted helminth infection and impact of four-monthly albendazole treatments in preschool children from semi-urban communities in Nigeria: a double-blind placebo-controlled randomised trial

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    Jackson Andrew L

    2009-02-01

    Full Text Available Abstract Background Children aged between one and five years are particularly vulnerable to disease caused by soil-transmitted helminths (STH. Periodic deworming has been shown to improve growth, micronutrient status (iron and vitamin A, and motor and language development in preschool children and justifies the inclusion of this age group in deworming programmes. Our objectives were to describe the prevalence and intensity of STH infection and to investigate the effectiveness of repeated four-monthly albendazole treatments on STH infection in children aged one to four years. Methods The study was carried out in four semi-urban villages situated near Ile-Ife, Osun State, Nigeria. The study was a double-blind placebo-controlled randomised trial. Children aged one to four years were randomly assigned to receive either albendazole or placebo every four months for 12 months with a follow-up at 14 months. Results The results presented here revealed that 50% of the preschool children in these semi-urban communities were infected by one or more helminths, the most prevalent STH being Ascaris lumbricoides (47.6%. Our study demonstrated that repeated four-monthly anthelminthic treatments with albendazole were successful in reducing prevalence and intensity of A. lumbricoides infections. At the end of the follow-up period, 12% and 43% of the children were infected with A. lumbricoides and mean epg was 117 (S.E. 50 and 1740 (S.E. 291 in the treatment and placebo groups respectively compared to 45% and 45% of the children being infected with Ascaris and mean epg being 1095 (S.E. 237 and 1126 (S.E. 182 in the treatment and placebo group respectively at baseline. Conclusion Results from this study show that the moderate prevalence and low intensity of STH infection in these preschool children necessitates systematic treatment of the children in child health programmes. Trial Registration Current controlled trials ISRCTN44215995.

  13. An in vivo evaluation of antimicrobial effects of Persica herbal mouthwash on Candida albicans and Enterococcus faecalis

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    Leila Shafiei Bafti

    2013-11-01

    Full Text Available BACKGROUND AND AIM: Due to their antimicrobial and dental plaque control activity, mouthwashes lead to an improvement in oral health. Although chemical mouthwashes have demonstrated the greatest antimicrobial and anti-inflammatory effects, their usage has been limited because of their numerous side effects. This study was conducted in vivo to determine the antibacterial and antifungal effects of Persica herbal mouthwash containing Salvadore persica, mint, and yarrow in comparison with a placebo. METHODS: In this experimental, single-blind study, 80 dentistry students, who were eager to participate in the study, were randomly allocated into two groups of forty. One group was given Persica while the other group received a placebo. They were asked to apply the mouthwash twice a day for four weeks. The participants were unaware of the mouthwash type. Saliva sampling was conducted in all cases before and after mouthwash application and the samples were dispatched to a laboratory for microbial culture (Sabouraud and Clark-Kenner media culture. After two weeks, the washout times in groups were swapped with each other and the sampling was conducted just like before. Finally, the data were analyzed using independent and paired t-test. P values of less than 0.05 were considered significant. RESULTS: The mean age of participants was 23.20 ± 4.14. Persica mouthwash significantly decreased the count of Candida albicans (1.43 ± 0.15 to 0.8 ± 0.35 (P < 0.001 and Enterococcus faecalis (0.93 ± 1.76 to 0.71 ± 2.10 (P = 0.008. CONCLUSION: The statistical tests revealed that applying Persica mouthwash would result in a significant decrease in the Candida albicans and Enterococcus faecalis count. Regarding the significant and desirable effect of Persica on Candida albicans and Enterococcus faecalis, and its herbal origin, its application could be suggested to reduce oral microbes and infections from fungi and enterococci.

  14. Differentiation of Candida albicans, Candida glabrata, and Candida krusei by FT-IR and chemometrics by CHROMagar™ Candida.

    Science.gov (United States)

    Wohlmeister, Denise; Vianna, Débora Renz Barreto; Helfer, Virginia Etges; Calil, Luciane Noal; Buffon, Andréia; Fuentefria, Alexandre Meneghello; Corbellini, Valeriano Antonio; Pilger, Diogo André

    2017-10-01

    Pathogenic Candida species are detected in clinical infections. CHROMagar™ is a phenotypical method used to identify Candida species, although it has limitations, which indicates the need for more sensitive and specific techniques. Infrared Spectroscopy (FT-IR) is an analytical vibrational technique used to identify patterns of metabolic fingerprint of biological matrixes, particularly whole microbial cell systems as Candida sp. in association of classificatory chemometrics algorithms. On the other hand, Soft Independent Modeling by Class Analogy (SIMCA) is one of the typical algorithms still little employed in microbiological classification. This study demonstrates the applicability of the FT-IR-technique by specular reflectance associated with SIMCA to discriminate Candida species isolated from vaginal discharges and grown on CHROMagar™. The differences in spectra of C. albicans, C. glabrata and C. krusei were suitable for use in the discrimination of these species, which was observed by PCA. Then, a SIMCA model was constructed with standard samples of three species and using the spectral region of 1792-1561cm -1 . All samples (n=48) were properly classified based on the chromogenic method using CHROMagar™ Candida. In total, 93.4% (n=45) of the samples were correctly and unambiguously classified (Class I). Two samples of C. albicans were classified correctly, though these could have been C. glabrata (Class II). Also, one C. glabrata sample could have been classified as C. krusei (Class II). Concerning these three samples, one triplicate of each was included in Class II and two in Class I. Therefore, FT-IR associated with SIMCA can be used to identify samples of C. albicans, C. glabrata, and C. krusei grown in CHROMagar™ Candida aiming to improve clinical applications of this technique. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. AFM force spectroscopy reveals how subtle structural differences affect the interaction strength between Candida albicans and DC-SIGN.

    Science.gov (United States)

    te Riet, Joost; Reinieren-Beeren, Inge; Figdor, Carl G; Cambi, Alessandra

    2015-11-01

    The fungus Candida albicans is the most common cause of mycotic infections in immunocompromised hosts. Little is known about the initial interactions between Candida and immune cell receptors, such as the C-type lectin dendritic cell-specific intracellular cell adhesion molecule-3 (ICAM-3)-grabbing non-integrin (DC-SIGN), because a detailed characterization at the structural level is lacking. DC-SIGN recognizes specific Candida-associated molecular patterns, that is, mannan structures present in the cell wall of Candida. The molecular recognition mechanism is however poorly understood. We postulated that small differences in mannan-branching may result in considerable differences in the binding affinity. Here, we exploit atomic force microscope-based dynamic force spectroscopy with single Candida cells to gain better insight in the carbohydrate recognition capacity of DC-SIGN. We demonstrate that slight differences in the N-mannan structure of Candida, that is, the absence or presence of a phosphomannan side chain, results in differences in the recognition by DC-SIGN as follows: (i) it contributes to the compliance of the outer cell wall of Candida, and (ii) its presence results in a higher binding energy of 1.6 kB T. The single-bond affinity of tetrameric DC-SIGN for wild-type C. albicans is ~10.7 kB T and a dissociation constant kD of 23 μM, which is relatively strong compared with other carbohydrate-protein interactions described in the literature. In conclusion, this study shows that DC-SIGN specifically recognizes mannan patterns on C. albicans with high affinity. Knowledge on the binding pocket of DC-SIGN and its pathogenic ligands will lead to a better understanding of how fungal-associated carbohydrate structures are recognized by receptors of the immune system and can ultimately contribute to the development of new anti-fungal drugs. Copyright © 2015 John Wiley & Sons, Ltd.

  16. Effect of salivary secretory IgA on the adhesion of Candida albicans to polystyrene.

    Science.gov (United States)

    San Millán, R; Elguezabal, N; Regúlez, P; Moragues, M D; Quindós, G; Pontón, J

    2000-09-01

    Attachment of Candida albicans to plastic materials of dental prostheses or to salivary macromolecules adsorbed on their surface is believed to be a critical event in the development of denture stomatitis. In an earlier study, it was shown that adhesion of C. albicans to polystyrene, a model system to study the adhesion of C. albicans to plastic materials, can be partially inhibited with an mAb directed against cell wall polysaccharides of C. albicans. In the present study, the role of whole saliva in the adhesion of C. albicans to polystyrene has been investigated, and three mAbs directed against epitopes of cell wall mannoproteins have been used to mimic the inhibitory effect observed with salivary secretory IgA (sIgA) on the adhesion of C. albicans to polystyrene. In the absence of whole saliva, adherence of C. albicans 3153 increased with germination. However, the presence of whole saliva enhanced the adhesion to polystyrene of C. albicans 3153 yeast cells but decreased the adhesion of germinated cells. The enhancement of adhesion of yeast cells to polystyrene mediated by saliva was confirmed with an agerminative mutant of C. albicans 3153. The inhibition of the adhesion of C. albicans 3153 germ tubes to polystyrene was due to the salivary sIgA since sIgA-depleted saliva enhanced the adhesion of C. albicans 3153 to polystyrene. The inhibitory effect mediated by sIgA was not related to the inhibition of germination but to the blockage of adhesins expressed on the cell wall surface of the germ tubes. The three mAbs studied reduced the adhesion of C. albicans 3153 to polystyrene at levels equivalent to those for purified sIgA. The highest reduction in the adhesion was obtained with the IgA mAb N3B. The best results were obtained when the three mAbs were combined. The results suggest that whole saliva plays a different role in the adhesion of C. albicans to polystyrene depending on the morphological phase of C. albicans. These results may give new insights into the

  17. Live Candida albicans Suppresses Production of Reactive Oxygen Species in Phagocytes▿ †

    Science.gov (United States)

    Wellington, Melanie; Dolan, Kristy; Krysan, Damian J.

    2009-01-01

    Production of reactive oxygen species (ROS) is an important aspect of phagocyte-mediated host responses. Since phagocytes play a crucial role in the host response to Candida albicans, we examined the ability of Candida to modulate phagocyte ROS production. ROS production was measured in the murine macrophage cell line J774 and in primary phagocytes using luminol-enhanced chemiluminescence. J774 cells, murine polymorphonuclear leukocytes (PMN), human monocytes, and human PMN treated with live C. albicans produced significantly less ROS than phagocytes treated with heat-killed C. albicans. Live C. albicans also suppressed ROS production in murine bone marrow-derived macrophages from C57BL/6 mice, but not from BALB/c mice. Live C. albicans also suppressed ROS in response to external stimuli. C. albicans and Candida glabrata suppressed ROS production by phagocytes, whereas Saccharomyces cerevisiae stimulated ROS production. The cell wall is the initial point of contact between Candida and phagocytes, but isolated cell walls from both heat-killed and live C. albicans stimulated ROS production. Heat-killed C. albicans has increased surface exposure of 1,3-β-glucan, a cell wall component that can stimulate phagocytes. To determine whether surface 1,3-β-glucan exposure accounted for the difference in ROS production, live C. albicans cells were treated with a sublethal dose of caspofungin to increase surface 1,3-β-glucan exposure. Caspofungin-treated C. albicans was fully able to suppress ROS production, indicating that suppression of ROS overrides stimulatory signals from 1,3-β-glucan. These studies indicate that live C. albicans actively suppresses ROS production in phagocytes in vitro, which may represent an important immune evasion mechanism. PMID:18981256

  18. Double-Stranded RNA Mycovirus Infection of Aspergillus fumigatus Is Not Dependent on the Genetic Make-Up of the Host

    NARCIS (Netherlands)

    Refos, Jeannine M.; Vonk, Alieke G.; Eadie, Kimberly; Lo-Ten-Foe, Jerome R.; Verbrugh, Henri A.; van Diepeningen, Anne D.; van de Sande, Wendy W. J.

    2013-01-01

    Aspergillus fumigatus is a fungus that causes opportunistic infections in immunocompromised patients, with high morbidity and mortality. In its turn, A. fumigatus can become infected with mycoviruses. Most mycoviruses have a dsRNA genome and can cause fungal hypovirulence. For that reason,

  19. Double-stranded RNA mycovirus infection of Aspergillus fumigatus is not dependent on the genetic make-up of the host

    NARCIS (Netherlands)

    Refos, Jeannine M; Vonk, Alieke G; Eadie, Kimberly; Lo-Ten-Foe, Jerome R; Verbrugh, Henri A; van Diepeningen, Anne D; van de Sande, Wendy W J

    2013-01-01

    Aspergillus fumigatus is a fungus that causes opportunistic infections in immunocompromised patients, with high morbidity and mortality. In its turn, A. fumigatus can become infected with mycoviruses. Most mycoviruses have a dsRNA genome and can cause fungal hypovirulence. For that reason,

  20. Development of a high-throughput Candida albicans biofilm chip.

    Directory of Open Access Journals (Sweden)

    Anand Srinivasan

    2011-04-01

    Full Text Available We have developed a high-density microarray platform consisting of nano-biofilms of Candida albicans. A robotic microarrayer was used to print yeast cells of C. albicans encapsulated in a collagen matrix at a volume as low as 50 nL onto surface-modified microscope slides. Upon incubation, the cells grow into fully formed "nano-biofilms". The morphological and architectural complexity of these biofilms were evaluated by scanning electron and confocal scanning laser microscopy. The extent of biofilm formation was determined using a microarray scanner from changes in fluorescence intensities due to FUN 1 metabolic processing. This staining technique was also adapted for antifungal susceptibility testing, which demonstrated that, similar to regular biofilms, cells within the on-chip biofilms displayed elevated levels of resistance against antifungal agents (fluconazole and amphotericin B. Thus, results from structural analyses and antifungal susceptibility testing indicated that despite miniaturization, these biofilms display the typical phenotypic properties associated with the biofilm mode of growth. In its final format, the C. albicans biofilm chip (CaBChip is composed of 768 equivalent and spatially distinct nano-biofilms on a single slide; multiple chips can be printed and processed simultaneously. Compared to current methods for the formation of microbial biofilms, namely the 96-well microtiter plate model, this fungal biofilm chip has advantages in terms of miniaturization and automation, which combine to cut reagent use and analysis time, minimize labor intensive steps, and dramatically reduce assay costs. Such a chip should accelerate the antifungal drug discovery process by enabling rapid, convenient and inexpensive screening of hundreds-to-thousands of compounds simultaneously.

  1. Candida albicans biofilm on titanium: effect of peroxidase precoating

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    Mohamed Ahariz

    2010-08-01

    Full Text Available Mohamed Ahariz1, Philippe Courtois1,21Laboratory of Experimental Hormonology, Université Libre de Bruxelles, Brussels, 2UER de Biologie Médicale, Haute Ecole Francisco Ferrer, Brussels, BelgiumAbstract: The present study aimed to document Candida albicans biofilm development on titanium and its modulation by a peroxidase-precoated material which can generate antimicrobials, such as hypoiodite or hypothiocyanite, from hydrogen peroxide, iodide, or thiocyanate. For this purpose, titanium (powder or foil was suspended in Sabouraud liquid medium inoculated with C. albicans ATCC10231. After continuous stirring for 2–21 days at room temperature, the supernatant was monitored by turbidimetry at 600 nm and titanium washed three times in sterile Sabouraud broth. Using the tetrazolium salt MTT-formazan assay, the titanium-adherent fungal biomass was measured as 7.50 ± 0.60 × 106 blastoconidia per gram of titanium powder (n = 30 and 0.50 ± 0.04 × 106 blastoconidia per cm² of titanium foil (n = 12. The presence of yeast on the surface of titanium was confirmed by microscopy both on fresh preparations and after calcofluor white staining. However, in the presence of peroxidase systems (lactoperoxidase with substrates such as hydrogen peroxide donor, iodide, or thiocyanate, Candida growth in both planktonic and attached phases appeared to be inhibited. Moreover, this study demonstrates the possible partition of peroxidase systems between titanium material (peroxidase-precoated and liquid environment (containing peroxidase substrates to limit C. albicans biofilm formation.Keywords: adhesion, material, oral, yeast

  2. Genoma de Candida albicans y resistencia a las drogas

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    Sandra Cruz Quintana

    2017-01-01

    Full Text Available Candida albicans es un importante patógeno fúngico en los humanos tanto por su importan - cia clínica como por su uso como un modelo experimental para la investigación científica. La comprensión de la biología de este patógeno es un requisito importante para la identificación de nuevas dianas de medicamentos para la terapia antifúngica. En esta revisión nos proponemos profundizar en las características del genoma de Candida albicans, su relación con la virulen - cia y cómo influye en la resistencia a las drogas antifùngicas, que nos permita comprender los mecanismos por los cuales ejerce su acción patógena y desarrollar otros enfoques en la búsqueda de nuevos antifúngicos. La revisión se realizó a través de los buscadores y plataformas HINARI , SciELO y MEDLINE . Se revisaron 40 revistas de impacto de la Web of Science relacionadas con el tema. Los descriptores empleados fueron: “genome of Candida albicans”, “drug resistance genes”, “dimorphism”, “virulence” y la combinación entre ellos y sus equivalentes en español. El análisis de los genomas fúngicos hace posible predecir el rol de genes con potencial terapéu - tico, con la secuenciación del genoma de Candida albicans ha aumentado la información sobre la función de los genes, entre los que destacan los posibles objetivos farmacológicos. El estudio del genoma de Candida albicans resulta imprescindible para diseñar en el futuro protocolos diagnósticos seguros, así como hallar nuevas dianas antifúngicas que permitan formular te - rapias más efectivas.

  3. Double Trouble

    NARCIS (Netherlands)

    Elsaesser, Thomas; Kievit, Robert; Simons, Jan

    1994-01-01

    Double Trouble highlights the career of Dutch scriptwriter and television producer Chiem van Houweninge, well-known for his long-running TV comedy series and as author of episodes for TV detective series. Double Trouble gives Van Houweninge's own views on writing and filming in television prime

  4. Menadione 処理した Candida albicans ROS 生産機構の解析

    OpenAIRE

    上野, 将明; 小笠原, 綾子; 渡部, 俊彦; 三上, 健; 松本, 達二; ウエノ, ユキヒロ; オガサワラ, アヤコ; ワタナベ, トシユキ; ミカミ, タケシ; マツモト, タツジ; Yukihiro, UENO; Ayako, OGASAWARA; Toshihiko, WATANABE; Takeshi, MIKAMI; Tatsuji, MATSUMOTO

    2008-01-01

    Menadione shows anti Condida activity by promoting ROS production. However, the ROS production mechanism has not been clarifield. Thus, in this study, we studied thr relation between anti Candida activity of menadione and ROS production. Menadione inhibited the growth of C. albicans BWP17 strain, the growth of C. albicans JM02 strain was not inhibited. ROS production in C. albicans BWP17 strain was enhanced by addition of menadione. The ROS production in C. albicans JM02 strain was also enhan...

  5. Antifungal activity of four honeys of different types from Algeria against pathogenic yeast: Candida albicans and Rhodotorula sp.

    OpenAIRE

    Ahmed Moussa; Djebli Noureddine; Aissat Saad; Meslem Abdelmelek; Benhalima Abdelkader

    2012-01-01

    Objective: To evaluate the antifungal activity of four honeys of different types from Algeria against pathogenic yeast i.e. Candida albicans (C. albicans) and Rhodotorula sp. Methods: Four Algeria honeys of different botanical origin were analyzed to test antifungal effect against C. albicans, and Rhodotorula sp. Different concentrations (undiluted, 10%, 30%, 50% and 70% w/v) of honey were studied in vitro for their antifugal activity using C. albicans and Rhodotorula sp. as fungal strains...

  6. Candida/Candida biofilms. First description of dual-species Candida albicans/C. rugosa biofilm.

    Science.gov (United States)

    Martins, Carlos Henrique Gomes; Pires, Regina Helena; Cunha, Aline Oliveira; Pereira, Cristiane Aparecida Martins; Singulani, Junya de Lacorte; Abrão, Fariza; Moraes, Thais de; Mendes-Giannini, Maria José Soares

    2016-04-01

    Denture liners have physical properties that favour plaque accumulation and colonization by Candida species, irritating oral tissues and causing denture stomatitis. To isolate and determine the incidence of oral Candida species in dental prostheses, oral swabs were collected from the dental prostheses of 66 patients. All the strains were screened for their ability to form biofilms; both monospecies and dual-species combinations were tested. Candida albicans (63 %) was the most frequently isolated microorganism; Candida tropicalis (14 %), Candida glabrata (13 %), Candida rugosa (5 %), Candida parapsilosis (3 %), and Candida krusei (2 %) were also detected. The XTT assay showed that C. albicans SC5314 possessed a biofilm-forming ability significantly higher (p biofilm was less than the total CFU of a monospecies C. albicans biofilm. In contrast to the profuse hyphae verified in monospecies C. albicans biofilms, micrographies showed that the C. albicans/non-albicans Candida biofilms consisted of sparse yeast forms and profuse budding yeast cells that generated a network. These results suggested that C. albicans and the tested Candida species could co-exist in biofilms displaying apparent antagonism. The study provide the first description of C. albicans/C. rugosa mixed biofilm. Copyright © 2016 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

  7. The efficacy of crude extract of Aloe secundiflora on Candida Albicans

    African Journals Online (AJOL)

    In- vitro studies on the efficacy of crude extracts of Aloe secundiflora on Candida albicans was conducted. Five mature leaves of Aloe secundiflora were collected and the crude extract was prepared, then autoclaved. The extract was then tested on Candida albicans grown on solid media. The results from these studies ...

  8. Efek Penambahan Glukosa pada Saburoud Dextrose Broth terhadap Pertumbuhan Candida albicans (Uji In Vitro

    Directory of Open Access Journals (Sweden)

    Lakshmi A. Leepel

    2012-10-01

    Full Text Available High carbohydrate intake is one of predisposing factors of oral candidiasis. Objective: Investigating the effect of 1%,5%,10% glucose addition on the growth of C.albicans in vitro. Method: C.albicans sample was taken from oral swab of a male oral candidiasis patient. Identification of C.albicans was conducted using CHROMagar and confirmed by germ tube formation in serum. As a comparison, C.albicans ATCC10231 was used. After 2 days the cultures were serially diluted and inoculated in SDB without glucose, and with 1%,5%,10% addditional glucose, kept for 3 and 7 days in room temperature, then inoculated in SDA. The CFU/ml were counted after 2 days. ANOVA with α0.05 was used. Result: Statisticaly, additional 1% glucose for 3 days lead to significant decreased of growth of both clinical strain and ATCC 10231 C. albicans. However, only additional 5% and 10% glucose in clinical isolate for 7 days increased the growth of C.albicans significantly. Conclusion: The effect of additional glucose on the increased growth of C.albicans in vitro is influenced by the concentration, exposure duration of glucose, and by the strain of C.albicans.DOI: 10.14693/jdi.v16i1.14

  9. Biochemical characterization of recombinant dihydroorotate dehydrogenase from the opportunistic pathogenic yeast Candida albicans

    DEFF Research Database (Denmark)

    Zameitat, E.; Gojkovic, Zoran; Knecht, Wolfgang

    2006-01-01

    Candida albicans is the most prevalent yeast pathogen in humans, and recently it has become increasingly resistant to the current antifungal agents. In this study we investigated C. albicans dihydroorotate dehydrogenase (DHODH, EC 1.3.99.11), which catalyzes the fourth step of de novo pyrimidine...

  10. The Mitochondrial GTPase Gem1 Contributes to the Cell Wall Stress Response and Invasive Growth of Candida albicans

    Directory of Open Access Journals (Sweden)

    Barbara Koch

    2017-12-01

    Full Text Available The interactions of mitochondria with the endoplasmic reticulum (ER are crucial for maintaining proper mitochondrial morphology, function and dynamics. This enables cells to utilize their mitochondria optimally for energy production and anabolism, and it further provides for metabolic control over developmental decisions. In fungi, a key mechanism by which ER and mitochondria interact is via a membrane tether, the protein complex ERMES (ER-Mitochondria Encounter Structure. In the model yeast Saccharomyces cerevisiae, the mitochondrial GTPase Gem1 interacts with ERMES, and it has been proposed to regulate its activity. Here we report on the first characterization of Gem1 in a human fungal pathogen. We show that in Candida albicans Gem1 has a dominant role in ensuring proper mitochondrial morphology, and our data is consistent with Gem1 working with ERMES in this role. Mitochondrial respiration and steady state cellular phospholipid homeostasis are not impacted by inactivation of GEM1 in C. albicans. There are two major virulence-related consequences of disrupting mitochondrial morphology by GEM1 inactivation: C. albicans becomes hypersusceptible to cell wall stress, and is unable to grow invasively. In the gem1Δ/Δ mutant, it is specifically the invasive capacity of hyphae that is compromised, not the ability to transition from yeast to hyphal morphology, and this phenotype is shared with ERMES mutants. As a consequence of the hyphal invasion defect, the gem1Δ/Δ mutant is drastically hypovirulent in the worm infection model. Activation of the mitogen activated protein (MAP kinase Cek1 is reduced in the gem1Δ/Δ mutant, and this function could explain both the susceptibility to cell wall stress and lack of invasive growth. This result establishes a new, respiration-independent mechanism of mitochondrial control over stress signaling and hyphal functions in C. albicans. We propose that ER-mitochondria interactions and the ER

  11. The Mitochondrial GTPase Gem1 Contributes to the Cell Wall Stress Response and Invasive Growth of Candida albicans.

    Science.gov (United States)

    Koch, Barbara; Tucey, Timothy M; Lo, Tricia L; Novakovic, Stevan; Boag, Peter; Traven, Ana

    2017-01-01

    The interactions of mitochondria with the endoplasmic reticulum (ER) are crucial for maintaining proper mitochondrial morphology, function and dynamics. This enables cells to utilize their mitochondria optimally for energy production and anabolism, and it further provides for metabolic control over developmental decisions. In fungi, a key mechanism by which ER and mitochondria interact is via a membrane tether, the protein complex ERMES (ER-Mitochondria Encounter Structure). In the model yeast Saccharomyces cerevisiae , the mitochondrial GTPase Gem1 interacts with ERMES, and it has been proposed to regulate its activity. Here we report on the first characterization of Gem1 in a human fungal pathogen. We show that in Candida albicans Gem1 has a dominant role in ensuring proper mitochondrial morphology, and our data is consistent with Gem1 working with ERMES in this role. Mitochondrial respiration and steady state cellular phospholipid homeostasis are not impacted by inactivation of GEM1 in C. albicans . There are two major virulence-related consequences of disrupting mitochondrial morphology by GEM1 inactivation: C. albicans becomes hypersusceptible to cell wall stress, and is unable to grow invasively. In the gem1 Δ / Δ mutant, it is specifically the invasive capacity of hyphae that is compromised, not the ability to transition from yeast to hyphal morphology, and this phenotype is shared with ERMES mutants. As a consequence of the hyphal invasion defect, the gem1 Δ / Δ mutant is drastically hypovirulent in the worm infection model. Activation of the mitogen activated protein (MAP) kinase Cek1 is reduced in the gem1 Δ / Δ mutant, and this function could explain both the susceptibility to cell wall stress and lack of invasive growth. This result establishes a new, respiration-independent mechanism of mitochondrial control over stress signaling and hyphal functions in C. albicans . We propose that ER-mitochondria interactions and the ER-Mitochondria Organizing

  12. Small but Crucial: The Novel Small Heat Shock Protein Hsp21 Mediates Stress Adaptation and Virulence in Candida albicans

    Science.gov (United States)

    Mayer, François L.; Wilson, Duncan; Jacobsen, Ilse D.; Miramón, Pedro; Slesiona, Silvia; Bohovych, Iryna M.; Brown, Alistair J. P.; Hube, Bernhard

    2012-01-01

    Small heat shock proteins (sHsps) have multiple cellular functions. However, the biological function of sHsps in pathogenic microorganisms is largely unknown. In the present study we identified and characterized the novel sHsp Hsp21 of the human fungal pathogen Candida albicans. Using a reverse genetics approach we demonstrate the importance of Hsp21 for resistance of C. albicans to specific stresses, including thermal and oxidative stress. Furthermore, a hsp21Δ/Δ mutant was defective in invasive growth and formed significantly shorter filaments compared to the wild type under various filament-inducing conditions. Although adhesion to and invasion into human-derived endothelial and oral epithelial cells was unaltered, the hsp21Δ/Δ mutant exhibited a strongly reduced capacity to damage both cell lines. Furthermore, Hsp21 was required for resisting killing by human neutrophils. Measurements of intracellular levels of stress protective molecules demonstrated that Hsp21 is involved in both glycerol and glycogen regulation and plays a major role in trehalose homeostasis in response to elevated temperatures. Mutants defective in trehalose and, to a lesser extent, glycerol synthesis phenocopied HSP21 deletion in terms of increased susceptibility to environmental stress, strongly impaired capacity to damage epithelial cells and increased sensitivity to the killing activities of human primary neutrophils. Via systematic analysis of the three main C. albicans stress-responsive kinases (Mkc1, Cek1, Hog1) under a range of stressors, we demonstrate Hsp21-dependent phosphorylation of Cek1 in response to elevated temperatures. Finally, the hsp21Δ/Δ mutant displayed strongly attenuated virulence in two in vivo infection models. Taken together, Hsp21 mediates adaptation to specific stresses via fine-tuning homeostasis of compatible solutes and activation of the Cek1 pathway, and is crucial for multiple stages of C. albicans pathogenicity. Hsp21 therefore represents the first

  13. Antimicrobial effects of Coleus amboinicus, Lour folium infusum towards Candida albicans and Streptococcus mutans

    Directory of Open Access Journals (Sweden)

    Devi Rianti

    2006-03-01

    Full Text Available A laboratory experimental study conducted on antimicrobial effects of Coleus amboinicus, Lour folium Infusum towards Candida albicans and Streptococcus mutans (S. mutans. Effective concentration of Coleus amboinicus, Lour to decrease the quantities Candida albicans and S. mutans colonies is expected to be found out in this study. This study was using Coleus Amboinicus, Lour folium infusum with 12.5%, 15%, 17.5%, 20%, and 22.5% concentrations. Sterilized aquadest used as a control. Candida albicans and S. mutans quantities was enumerated by counting the amount of Candida albicans and S. mutans growth in the Sabouraud ,s dextrose agar and Tryptone and yeast Agar media, using Colony Forming Unit per milliliter (CFU/ ml unit. Data analysis was using a One-Way ANOVA and LSD with 5% degree of significance. The result showed 22.5% concentration of CAL folium infusum was the most effective in decreasing the quantity Candida albicans and S. mutans colonies.

  14. Whole Saliva has a Dual Role on the Adherence of Candida albicans to Polymethylmetacrylate.

    Science.gov (United States)

    Elguezabal, N; Maza, J L; Dorronsoro, S; Pontón, J

    2008-01-01

    Adhesion of Candida albicans to acrylic of dental prostheses or to salivary macromolecules adsorbed on their surface is believed to be a critical event in the development of denture stomatitis. In previous studies our group has shown that adhesion of C. albicans germ tubes to polystyrene is decreased by saliva whereas C. albicans yeast cells adhesion to the same material is enhanced. The results presented in this study confirm this dual role played by whole saliva, since it decreased the adhesion of germ tubes but increased the adhesion of yeast cells to polymethylmetacrylate (PMMA). These effects mediated by whole saliva do not seem to be related to an inhibition of the germination of C. albicans, since similar levels of filamentation were observed in presence and absence of saliva. These results may give new insights into the conflicting role of saliva in the adhesion of C. albicans to acrylic resins of dental prostheses.

  15. Candida albicans orf19.3727 encodes phytase activity and is essential for human tissue damage

    Science.gov (United States)

    Fong, Wing-Ping; Samaranayake, Lakshman Perera

    2017-01-01

    Candida albicans is a clinically important human fungal pathogen. We previously identified the presence of cell-associated phytase activity in C. albicans. Here, we reveal for the first time, that orf19.3727 contributes to phytase activity in C. albicans and ultimately to its virulence potency. Compared with its wild type counterpart, disruption of C. albicans orf19.3727 led to decreased phytase activity, reduced ability to form hyphae, attenuated in vitro adhesion, and reduced ability to penetrate human epithelium, which are the major virulence attributes of this yeast. Thus, orf19.3727 of C. albicans plays a key role in fungal pathogenesis. Further, our data uncover a putative novel strategy for anti-Candidal drug design through inhibition of phytase activity of this common pathogen. PMID:29216308

  16. POTENSI ANTIMIKROBIA KRIM EKSTRAK RANTING PATAH TULANG (Euphorbia tirucalli Linn. TERHADAP Propionibacterium acnes ATCC 11827 DAN Candida albicans ATCC 24433

    Directory of Open Access Journals (Sweden)

    Melina Scandinovita Setiorini

    2016-04-01

    extracts with cream for testing Candida albicans.The final results were 10% test extract had MIC to Propionibacterium acnes and 6% test extract had MIC in cream to Candida albicans. Keywords: Euphorbia tirucalli L., DMSO, Thymol, antimicrobial potency, cream (o/w, Propionibacterium acnes, Candida albicans

  17. The role and relevance of phospholipase D1 during growth and dimorphism of Candida albicans.

    Science.gov (United States)

    Hube, B; Hess, D; Baker, C A; Schaller, M; Schäfer, W; Dolan, J W

    2001-04-01

    The phosphatidylcholine-specific phospholipase D1 (PLD1) in Saccharomyces cerevisiae is involved in vesicle transport and is essential for sporulation. The gene encoding the homologous phospholipase D1 from Candida albicans (PLD1) was used to study the role of PLD1 in this pathogenic fungus. In vitro and in vivo expression studies using Northern blots and reverse transcriptase-PCR showed low PLD1 mRNA levels in defined media supporting yeast growth and during experimental infection, while enhanced levels of PLD1 transcripts were detected during the yeast to hyphal transition. To study the relevance of PLD1 during yeast and hyphal growth, an essential part of the gene was deleted in both alleles of two isogenic strains. In vitro PLD1 activity assays showed that pld1 mutants produced no detectable levels of phosphatidic acid, the hydrolytic product of PLD1 activity, and strongly reduced levels of diacylglycerol, the product of lipid phosphate phosphohydrolase, suggesting no or a negligible background PLD1 activity in the pld1 mutants. The pld1 mutants showed no growth differences compared to the parental wild-type in liquid complex and minimal media, independent of the growth temperature. In addition, growth rates of pld1 mutants in media with protein as the sole source of nitrogen were similar to growth rates of the wild-type, indicating that secretion of proteinases was not reduced. Chlamydospore formation was normal in pld1 mutants. When germ tube formation was induced in liquid media, pld1 mutants showed similar rates of yeast to hyphal transition compared to the wild-type. However, no hyphae formation was observed on solid Spider medium, and cell growth on cornmeal/Tween 80 medium indicated aberrant morphogenesis. In addition, pld1 mutants growing on solid media had an attenuated ability to invade the agar. In a model of oral candidosis, pld1 mutants showed no attenuation of virulence. In contrast, the mutant was less virulent in two different mouse models

  18. An in vitro Model for Oral Mixed Biofilms of Candida albicans and Streptococcus gordonii in Synthetic Saliva

    Directory of Open Access Journals (Sweden)

    Daniel eMontelongo-Jauregui

    2016-05-01

    Full Text Available As a member of the normal human oral microbiota, the fungus C. albicans is often found in association with Streptococcus gordonii, a member of dental plaque forming bacteria. Evidence suggests that S. gordonii serves as a facilitator of C. albicans adherence to dental tissues, which represents a clinically relevant problem, particularly for immunocompromised individuals that could subsequently develop fungal infections. In this study we describe the development of a relatively simple and economical in vitro model that allows for the growth of mixed bacterial/fungal biofilms in 96-well microtiter plates. We have applied this method to test and compare the growth characteristics of single and dual species biofilms in traditional microbiological media versus a synthetic saliva medium (basal medium mucin, BMM that more closely resembles physiological conditions within the oral cavity. Results indicated a synergistic effect for the formation of biofilms when both microorganisms were seeded together under all conditions tested. The structural and architectural features of the resulting biofilms were further characterized using scanning electron microscopy (SEM and confocal scanning laser microscopy (CSLM. We also performed drug susceptibility assays against single and mixed species biofilms using commonly used antifungals and antibacterial antibiotics, both in monotherapy and in combination therapy, for a direct comparison of resistance against antimicrobial treatment. As expected, mixed species biofilms displayed higher levels of resistance to antimicrobial treatment at every dose tested in both traditional media and BMM synthetic saliva, as compared to single-species biofilms.

  19. Synergistic antifungal effect of chitosan-stabilized selenium nanoparticles synthesized by pulsed laser ablation in liquids against Candida albicans biofilms.

    Science.gov (United States)

    Lara, Humberto H; Guisbiers, Gregory; Mendoza, Jonathan; Mimun, Lawrence C; Vincent, Brandy A; Lopez-Ribot, Jose L; Nash, Kelly L

    2018-01-01

    Candida albicans is a major opportunistic fungal pathogen. One of the most important virulence factors that contribute to the pathogenesis of candidiasis is its ability to form biofilms. A key characteristic of Candida biofilms is their resistance to antifungal agents. Due to significant morbidity and mortality rates related to biofilm-associated drug resistance, there is an urgency to develop novel nanotechnology-based approaches preventing biofilm-related infections. In this study, we report, for the first time, the synthesis of selenium nanoparticles by irradiating selenium pellets by nanosecond pulsed laser ablation in liquid chitosan as a capping agent. Synergy of the fungicidal effect of selenium nanoparticles and chitosan was quantified by the combination index theorem of Chou-Talalay. This drug combination resulted in a potent fungicidal effect against a preformed C. albicans biofilm in a dose-response manner. By advanced electron microscopy techniques, we documented the adhesive and permeabilizing properties of chitosan, therefore allowing selenium nanoparticles to enter as the cell wall of the yeast became disrupted and distorted. Most importantly, we demonstrated a potent quantitative synergistic effect when compounds such as selenium and chitosan are combined. These chitosan-stabilized selenium nanoparticles could be used for ex vivo applications such as sterilizers for surfaces and biomedical devices.

  20. The Effect of Gold Nano Particles Compared to Dioxide Titanium Nano Particles on Vital Factors of Isolated Candida albicans in Patients with Oral Candidiasis in Vitro

    Directory of Open Access Journals (Sweden)

    Ladan Rahimzadeh Torabi

    2016-12-01

    Full Text Available Background Oral Candidiasis is fungal infection that affects the oral cavity. Oral infections caused by yeast of the genus Candida and particularly Candida albicans (oral candidiasis have been recognized throughout recorded history. Objectives The aim of this study was to compare the antifungal effects of gold nanoparticles and dioxide titanium nanoparticles on patients with Oral Candidiasis patients. This review is to give the reader a contemporary overview of oral candidiasis, the organisms involved, and the management strategies that are currently employed or could be utilized in the future. Methods This experimental study has been done in Isfahan city totally with 56 numbers of patients suffering from Candidiasis in groups of different ages from hospitals and laboratories The resulted from swap in Sabouraud Dexteros agar and finally with complementary experiments 56 isolated Candida albicans (oral Candidiasis detected and grew in culture milieu then gold nanoparticles (10 nanometers and titanium dioxide nanoparticles (10 - 15 nanometers in different consistencies add to this milieu and the least density of halting and the least density of killing fungi for different suspension thinness containing Candida albicans. The data were analyzed by spss 15 version software. Results The results showed that gold nanoparticles have a good anticandidial effects and can be used to treat infections of Candida, it is recommended that further research considered the effects of different infections candidiasis in In vitro condition. Conclusions Using gold nanoparticles with 10 nanometer diameters have high antifungal effect on oral candidiasis and its function has been proved. In current study halting effect of gold nanoparticles on micro-organisms experimented in different densities was observed.

  1. Female genital tract bacterial coisolates with Candida albicans in patients without clinical vaginitis.

    Science.gov (United States)

    Monif, G R; Carson, H J

    1998-01-01

    In vitro, Candida albicans has demonstrated the ability to inhibit replication of selected bacteria. Little information exists on the impact of C. albicans on the vaginal bacterial flora in vivo. The purpose of this study is to identify the coexisting bacterial flora when C. albicans is isolated from vaginal cultures submitted to a hospital-based testing facility for reasons other than vulvovaginitis. All specimens (240) received from ambulatory care clinics over a six-month period were cultured for aerobic and anaerobic bacteria and Candida species. Those specimens submitted for cervicitis, vaginitis, or vaginal discharge and those from which yeasts other than C. albicans were isolated were eliminated. To control for sample biases, a subgroup composed of all pregnant women for whom cultures were done as screening procedures was similarly studied. Chi-square analyses, comparing the prevalence of individual bacteria isolated with and without the presence of C. albicans, were done for all study populations using SPSS for Windows software (1994). Two hundred and forty consecutive specimens were bacteriologically analyzed. Of the 220 vaginal samples used in the study, C. albicans was isolated in 44 instances (20%). Neither the presence of the lactobacilli nor the presence of Gardnerella vaginalis markedly influenced the isolation rate of C. albicans. The group B streptococci had a greater probability of coisolation when C. albicans was present (27.3% verses 16%), but this was not statistically significant (P aerobic bacilli was reduced in the presence of C. albicans (30/176 [17.1%] versus 6/44 [13.6%]), this reduced incidence was not statistically significant. Isolation data of the subgroup of pregnant women supported these observations. Within the limitations of the study, statistically, the data suggests that an inverse relationship exists between the presence of C. albicans and recovery of Peptostreptococcus and anaerobic gram-positive cocci and bacilli.

  2. Decrease in Infection Rate Following Use of Povidone-Iodine During Transrectal Ultrasound Guided Biopsy of the Prostate: A Double Blind Randomized Clinical Trial

    International Nuclear Information System (INIS)

    Ghafoori, Mahyar; Shakiba, Madjid; Seifmanesh, Hamidreza; Hoseini, Kamal

    2012-01-01

    Infection after transrectal ultrasound (TRUS) guided biopsy of the prostate is a major and potentially life-threatening problem. Using antibiotic premedication can not completely eliminate infection after biopsy. We performed this study to determine the value of using povidone-iodine in prevention of post biopsy infection. Totally, 280 patients who were referred for TRUS guided biopsy of the prostate were divided randomly into two equal groups. The case group received an intrarectal mixture of povidone-iodine and lidocaine gel before performing biopsy, while the control group received only lidocaine gel. Patients were followed up for 30 days for possible signs of infection including fever, chills and dysuria. The mean age in the case group was 68.7 ± 7 years and 68.1 ± 7 years in the control group (P = 0.78). Overall, there were signs and symptoms of infection in 78 patients (27.9%), of which 27 (19.3%) were in the case group, while 51 (36.4%) were in the control group (P = 0.001, OR = 2.4, 95% CI = 1.4-4.1). Simple use of widely available povidone-iodine for cleaning the rectum before TRUS guided prostate biopsy can reduce the infection rate

  3. Morphology-Independent Virulence of Candida Species during Polymicrobial Intra-abdominal Infections with Staphylococcus aureus.

    Science.gov (United States)

    Nash, Evelyn E; Peters, Brian M; Fidel, Paul L; Noverr, Mairi C

    2016-01-01

    Intra-abdominal polymicrobial infections cause significant morbidity and mortality. An experimental mouse model of Candida albicans-Staphylococcus aureus intra-abdominal infection (IAI) results in 100% mortality by 48 to 72 h postinoculation, while monomicrobial infections are avirulent. Mortality is associated with robust local and systemic inflammation without a requirement for C. albicans morphogenesis. However, the contribution of virulence factors coregulated during the yeast-to-hypha transition is unknown. This also raised the question of whether other Candida species that are unable to form hyphae are as virulent as C. albicans during polymicrobial IAI. Therefore, the purpose of this study was to evaluate the ability of non-albicans Candida (NAC) species with various morphologies and C. albicans transcription factor mutants (efg1/efg1 and cph1/cph1) to induce synergistic mortality and the accompanying inflammation. Results showed that S. aureus coinoculated with C. krusei or C. tropicalis was highly lethal, similar to C. albicans, while S. aureus-C. dubliniensis, S. aureus-C. parapsilosis, and S. aureus-C. glabrata coinoculations resulted in little to no mortality. Local and systemic interleukin-6 (IL-6) and prostaglandin E2 (PGE2) levels were significantly elevated during symptomatic and/or lethal coinfections, and hypothermia strongly correlated with mortality. Coinoculation with C. albicans strains deficient in the transcription factor Efg1 but not Cph1 reversed the lethal outcome. These results support previous findings and demonstrate that select Candida species, without reference to any morphological requirement, induce synergistic mortality, with IL-6 and PGE2 acting as key inflammatory factors. Mechanistically, signaling pathways controlled by Efg1 are critical for the ability of C. albicans to induce mortality from an intra-abdominal polymicrobial infection. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  4. Profil des germes impliqués dans les infections cervicovaginales ...

    African Journals Online (AJOL)

    La prévalence des infections était de 70,59%. Les germes rencontrés étaient Candida albicans 32,35%, Gardnerella vaginalis 30,39%, Staphylococcus aureus 8,82%, Streptococcus spp 1,96%, les entérobactéries 11,78% et le trichomonas vaginalis 1%. C.albicans a montré une résistance à l'Amphotéricime B 41 ,94 % et ...

  5. Candida albicans menengitis in a newborn with classical galactosemia

    Directory of Open Access Journals (Sweden)

    Hüseyin Altunhan

    2012-12-01

    Full Text Available Classical galactosemia is a rarely seen carbohydrate metabolismdisorder. The frequency of sepsis significantlyincreases in patients with galactosemia. The most commonagent causing sepsis is E. coli. Sepsis due to fungusin patients with galactosemia is rarely reported. Candidais an important cause of sepsis in newborn intensive careunits especially in newborns with underlying risk factorssuch as prematurity and low birth weight. Although themost common etiologic agent of sepsis is E. coli in caseswith galactosemia, it should be kept in mind that candidamay also be causative agent of sepsis and meningitis inthese patients even though there is no underlying risk factor.Also the clinical and laboratory findings of candidiasismay be obscure. For this reason, especially in newborncandida meningitis, the index of suspicion should be kepthigh for early diagnosis and treatment. In such patientscerebrospinal fluid analysis, culture and brain imagingshould be done necessarily, because early diagnosis andtreatment will be life saving. In this article we reported agalactosemia case with the diagnosis of meningitis andCandida albicans grown in his blood culture derived onthe fourth day of admission to clinic.Key words: Candida albicans, galactosemia, meningitis,newborn, sepsis

  6. Mechanism of iron uptake by the pathogenic yeast, Candida albicans

    International Nuclear Information System (INIS)

    Ismail, A.

    1986-01-01

    C. albicans requires iron for growth and phenotypic development. When deprived of iron, mycelium and bud formation was suppressed. Survival of the organism was also reduced under iron-limiting conditions. The combination of elevated temperature and iron-deprivation further reduced phenotypic development and survival of the yeast. The combination of elevated temperature and iron starvation resulted in a decrease in both the growth rate and siderophore production. However, with time, the cells were able to show partial recovery in the growth rate which occurred concomitantly with an increase in siderophore production. In order for siderophores to be utilized, ferri-siderophore receptors must be produced. The receptor was shown to be located in the plasma membrane of the yeast. Scatchard analysis of the binding of ferri-siderophores to plasma membrane receptors showed an increase in receptor affinity and number of binding sites in iron-starved cells when compared to control cells. Autoradiograms of the 58 Fe-siderophore-protein complex following SDS-PAGE separation of candidal proteins revealed the presence of a ferri-siderophore receptor of approximately 10,000 daltons. C. albicans strains which lacked the ability to synthesize phenolate siderophore maintained a phenolate receptor and bound candidal phenolate siderophore better than non-candidal phenolate siderophores

  7. Prevalence of Candida albicans and Candida dubliniensis in caries-free and caries-active children in relation to the oral microbiota-a clinical study.

    Science.gov (United States)

    Al-Ahmad, A; Auschill, T M; Dakhel, R; Wittmer, A; Pelz, K; Heumann, C; Hellwig, E; Arweiler, N B

    2016-11-01

    The correlation between caries and the oral prevalence of Candida spp. in children is contradictory in literature. Thereby, authors focused on Candida albicans as the most isolated Candida species from the oral cavity. Therefore, the aim of the present study was to compare caries-free and caries-bearing children regarding their oral carriage of Candida spp. Twenty-six caries-free (CF group) and 26 caries-active children (CA group) were included into this study. Three different types of specimens were assessed, saliva and plaque, and in the case of caries, infected dentine samples were microbiologically analyzed for aerobic and anaerobic microorganisms and their counts. Special attention was given to the differentiation between C. albicans and Candida dubliniensis. Additionally, different biochemical tests, VITEK 2 (VITEK®2, bioMérieux, Marcy-l'Etoile, France) and 16S and 18S ribosomal DNA (rDNA) sequencing, were applied for identification. The detection of C. albicans did not differ between the CF and CA groups. C. dubliniensis was never detected in any specimen of the CF group, but occurred in one quarter of the CA group (27 % in plaque, 23 % in saliva), thus leading to a statistically significant difference between the two groups (p oral Candida species-is an important determinant for identifying etiological factors of dental caries in children.

  8. The European Confederation of Medical Mycology (ECMM) survey of candidaemia in Italy: in vitro susceptibility of 375 Candida albicans isolates and biofilm production.

    Science.gov (United States)

    Tortorano, Anna Maria; Prigitano, Anna; Biraghi, Emanuela; Viviani, Maria Anna

    2005-10-01

    To investigate the in vitro antifungal susceptibility pattern of 375 Candida albicans bloodstream isolates recovered during the European Confederation of Medical Mycology survey of candidaemia performed in Lombardia, Italy and to test the ability to form biofilm. In vitro susceptibility to flucytosine, fluconazole, itraconazole, posaconazole, voriconazole and caspofungin was performed by broth microdilution following the NCCLS guidelines. Biofilm production was measured using the XTT reduction assay in 59 isolates selected as representative of different patterns of susceptibility to flucytosine and azoles. MICs (mg/L) at which 90% of the strains were inhibited were < or =0.25 for flucytosine, 0.25 for caspofungin, 4 for fluconazole and 0.06 for itraconazole, voriconazole and posaconazole. Flucytosine resistance was detected in five isolates and was associated with serotype B in 2/29 and serotype A in 3/346. Resistance to fluconazole was detected in 10 isolates; nine of these exhibited reduced susceptibility to the other azoles. Among the 10 patients with fluconazole-resistant C. albicans bloodstream infection, only one, an AIDS patient, had been previously treated with fluconazole. Biofilm production was observed in 23 isolates (39%) and was significantly associated with serotype B. No relationship was detected with the pattern of antifungal susceptibility. Resistance is uncommon in C. albicans isolates recovered from blood cultures, while biofilm production is a relatively frequent event. Periodic surveillance is warranted to monitor the incidence of in vitro antifungal resistance as well as of biofilm production.

  9. Microbicidal activity of neutrophils is inhibited by isolates from recurrent vaginal candidiasis (RVVC) caused by Candida albicans through fungal thioredoxin reductase.

    Science.gov (United States)

    Ratti, Bianca Altrão; Godoy, Janine Silva Ribeiro; de Souza Bonfim Mendonça, Patrícia; Bidóia, Danielle Lazarin; Nakamura, Tânia Ueda; Nakamura, Celso Vataru; Lopes Consolaro, Marcia Edilaine; Estivalet Svidzinski, Terezinha Inez; de Oliveira Silva, Sueli

    2015-01-01

    Vulvovaginal candidiasis (VVC) is characterized by an infection of the vulva and vagina, mainly caused by Candida albicans, a commensal microorganism that inhabits the vaginal, digestive, and respiratory mucosae. Vulvovaginal candidiasis affects approximately 75% of women, and 5% develop the recurrent form (RVVC). The aim of the present study was to evaluate whether neutrophils microbicidal response is triggered when activated with RVVC isolates caused by C. albicans. Our results showed that RVVC isolates induced neutrophil migration but significantly decrease the microbicidal activity of neutrophils, compared with VVC and ASS isolates. The microbicidal activity of neutrophils is highly dependent on the production of reactive oxygen species/reactive nitrogen species (ROS/RNS). However, this isolate induced detoxification of ROS/RNS produced by neutrophils, reflected by the high level of thiol groups and by the oxygen consumption. Therefore, RVVC isolates induced biochemical changes in the inflammatory response triggered by neutrophils, and these effects were mainly related to the detoxification of ROS/RNS through the thioredoxin reductase (TR), a key antioxidant enzyme in fungi. This might be one of the resistance mechanisms triggered by RVVC caused by C. albicans. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Lipidomics of Candida albicans biofilms reveals phase-dependent production of phospholipid molecular classes and role for lipid rafts in biofilm formation.

    Science.gov (United States)

    Lattif, Ali Abdul; Mukherjee, Pranab K; Chandra, Jyotsna; Roth, Mary R; Welti, Ruth; Rouabhia, Mahmoud; Ghannoum, Mahmoud A

    2011-11-01

    Candida albicans-associated bloodstream infections are linked to the ability of this yeast to form biofilms. In this study, we used lipidomics to compare the lipid profiles of C. albicans biofilms and planktonic cells, in early and mature developmental phases. Our results showed that significant differences exist in lipid composition in both developmental phases. Biofilms contained higher levels of phospholipid and sphingolipids than planktonic cells (nmol per g biomass, Pbiofilms compared to planktonic cells (P≤0.05). The ratio of phosphatidylcholine to phosphatidylethanolamine was lower in biofilms compared to planktonic cells in both early (1.17 vs 2.52, P≤0.001) and late (2.34 vs 3.81, P≤0.001) developmental phases. The unsaturation index of phospholipids decreased with time, with this effect being particularly strong for biofilms. Inhibition of the biosynthetic pathway for sphingolipid [mannosyl diinositolphosphoryl ceramide, M(IP)₂C] by myriocin or aureobasidin A, and disruption of the gene encoding inositolphosphotransferase (Ipt1p), abrogated the ability of C. albicans to form biofilms. The differences in lipid profiles between biofilms and planktonic Candida cells may have important implications for the biology and antifungal resistance of biofilms.

  11. A randomized, double-blind, comparative study to assess the safety and efficacy of topical retapamulin ointment 1% versus oral linezolid in the treatment of secondarily infected traumatic lesions and impetigo due to methicillin-resistant Staphylococcus aureus.

    Science.gov (United States)

    Tanus, Tonny; Scangarella-Oman, Nicole E; Dalessandro, Marybeth; Li, Gang; Breton, John J; Tomayko, John F

    2014-12-01

    To evaluate the clinical and bacteriological efficacy of topical retapamulin ointment 1% versus oral linezolid in the treatment of patients with secondarily infected traumatic lesions (SITLs; excluding abscesses) or impetigo due to methicillin-resistant Staphylococcus aureus (MRSA). A randomized, double-blind, double-dummy, multicenter, comparative study (NCT00852540). Patients recruited from 36 study centers in the United States. Patients 2 months or older with SITL (including secondarily infected lacerations or sutured wounds) or impetigo (bullous and nonbullous) suitable for treatment with a topical antibiotic, with a total Skin Infection Rating Scale score of 8 or greater, including a pus/exudate score of 3 or greater. Patients received retapamulin ointment 1% (plus oral placebo), twice daily for 5 days or oral linezolid (plus placebo ointment) 2 or 3 times daily for 10 days. Primary end point: clinical response (success/failure) at follow-up in patients with MRSA at baseline (per-protocol population). Secondary efficacy end points: clinical and microbiologic response and outcome at follow-up and end of therapy; therapeutic response at follow-up. The majority of patients had SITL (70.4% [188/267] and 66.4% [91/137] in the retapamulin and linezolid groups, respectively; intent-to-treat clinical population). Clinical success rate at follow-up was significantly lower in the retapamulin versus the linezolid group (63.9% [39/61] vs 90.6% [29/32], respectively; difference in success rate -26.7%; 95% CI, -45.7 to -7.7). Clinical success rate at follow-up in the per-protocol MRSA population was significantly lower in the retapamulin versus the linezolid group. It could not be determined whether this was related to study design, bacterial virulence, or retapamulin activity.

  12. Sequence variations and protein expression levels of the two immune evasion proteins Gpm1 and Pra1 influence virulence of clinical Candida albicans isolates.

    Science.gov (United States)

    Luo, Shanshan; Hipler, Uta-Christina; Münzberg, Christin; Skerka, Christine; Zipfel, Peter F

    2015-01-01

    Candida albicans, the important human fungal pathogen uses multiple evasion strategies to control, modulate and inhibit host complement and innate immune attack. Clinical C. albicans strains vary in pathogenicity and in serum resistance, in this work we analyzed sequence polymorphisms and variations in the expression levels of two central fungal complement evasion proteins, Gpm1 (phosphoglycerate mutase 1) and Pra1 (pH-regulated antigen 1) in thirteen clinical C. albicans isolates. Four nucleotide (nt) exchanges, all representing synonymous exchanges, were identified within the 747-nt long GPM1 gene. For the 900-nt long PRA1 gene, sixteen nucleotide exchanges were identified, which represented synonymous, as well as non-synonymous exchanges. All thirteen clinical isolates had a homozygous exchange (A to G) at position 73 of the PRA1 gene. Surface levels of Gpm1 varied by 8.2, and Pra1 levels by 3.3 fold in thirteen tested isolates and these differences influenced fungal immune fitness. The high Gpm1/Pra1 expressing candida strains bound the three human immune regulators more efficiently, than the low expression strains. The difference was 44% for Factor H binding, 51% for C4BP binding and 23% for plasminogen binding. This higher Gpm1/Pra1 expressing strains result in enhanced survival upon challenge with complement active, Factor H depleted human serum (difference 40%). In addition adhesion to and infection of human endothelial cells was increased (difference 60%), and C3b surface deposition was less effective (difference 27%). Thus, variable expression levels of central immune evasion protein influences immune fitness of the human fungal pathogen C. albicans and thus contribute to fungal virulence.

  13. Exchange of adsorbed serum proteins during adhesion of Staphylococcus aureus to an abiotic surface and Candida