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Sample records for candida albicans infection

  1. Adaptive immune responses to Candida albicans infection.

    Science.gov (United States)

    Richardson, Jonathan P; Moyes, David L

    2015-01-01

    Fungal infections are becoming increasingly prevalent in the human population and contribute to morbidity and mortality in healthy and immunocompromised individuals respectively. Candida albicans is the most commonly encountered fungal pathogen of humans, and is frequently found on the mucosal surfaces of the body. Host defense against C. albicans is dependent upon a finely tuned implementation of innate and adaptive immune responses, enabling the host to neutralise the invading fungus. Central to this protection are the adaptive Th1 and Th17 cellular responses, which are considered paramount to successful immune defense against C. albicans infections, and enable tissue homeostasis to be maintained in the presence of colonising fungi. This review will highlight the recent advances in our understanding of adaptive immunity to Candida albicans infections.

  2. Innate immune cell response upon Candida albicans infection.

    Science.gov (United States)

    Qin, Yulin; Zhang, Lulu; Xu, Zheng; Zhang, Jinyu; Jiang, Yuan-Ying; Cao, Yongbing; Yan, Tianhua

    2016-07-01

    Candida albicans is a polymorphic fungus which is the predominant cause of superficial and deep tissue fungal infections. This microorganism has developed efficient strategies to invade the host and evade host defense systems. However, the host immune system will be prepared for defense against the microbe by recognition of receptors, activation of signal transduction pathways and cooperation of immune cells. As a consequence, C. albicans could either be eliminated by immune cells rapidly or disseminate hematogenously, leading to life-threatening systemic infections. The interplay between Candida albicans and the host is complex, requiring recognition of the invaded pathogens, activation of intricate pathways and collaboration of various immune cells. In this review, we will focus on the effects of innate immunity that emphasize the first line protection of host defense against invaded C. albicans including the basis of receptor-mediated recognition and the mechanisms of cell-mediated immunity. PMID:27078171

  3. Rat indwelling urinary catheter model of Candida albicans biofilm infection.

    Science.gov (United States)

    Nett, Jeniel E; Brooks, Erin G; Cabezas-Olcoz, Jonathan; Sanchez, Hiram; Zarnowski, Robert; Marchillo, Karen; Andes, David R

    2014-12-01

    Indwelling urinary catheters are commonly used in the management of hospitalized patients. Candida can adhere to the device surface and propagate as a biofilm. These Candida biofilm communities differ from free-floating Candida, exhibiting high tolerance to antifungal therapy. The significance of catheter-associated candiduria is often unclear, and treatment may be problematic considering the biofilm drug-resistant phenotype. Here we describe a rodent model for the study of urinary catheter-associated Candida albicans biofilm infection that mimics this common process in patients. In the setting of a functioning, indwelling urinary catheter in a rat, Candida proliferated as a biofilm on the device surface. Characteristic biofilm architecture was observed, including adherent, filamentous cells embedded in an extracellular matrix. Similar to what occurs in human patients, animals with this infection developed candiduria and pyuria. Infection progressed to cystitis, and a biofilmlike covering was observed over the bladder surface. Furthermore, large numbers of C. albicans cells were dispersed into the urine from either the catheter or bladder wall biofilm over the infection period. We successfully utilized the model to test the efficacy of antifungals, analyze transcriptional patterns, and examine the phenotype of a genetic mutant. The model should be useful for future investigations involving the pathogenesis, diagnosis, therapy, prevention, and drug resistance of Candida biofilms in the urinary tract.

  4. Endoftalmite por Candida albicans Candida albicans endophthalmitis

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    Pedro Duraes Serracarbassa

    2003-10-01

    Full Text Available O autor descreve os aspectos epidemiológicos, histopatológicos e clínicos da endoftalmite endógena por Candida albicans. Apresenta ainda novos métodos diagnósticos e opções terapêuticas utilizadas no tratamento das infecções fúngicas intra-oculares, por meio de revisão bibliográfica.The author describes epidemiological, histopathological and clinical aspects of endogenous Candida albicans endophthalmitis. He also presents new diagnostic methods and therapeutical options to treat intraocular fungal infections, based on literature review.

  5. 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

  6. Zebrafish Egg Infection Model for Studying Candida albicans Adhesion Factors.

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    Yin-Zhi Chen

    Full Text Available Disseminated candidiasis is associated with 30-40% mortality in severely immunocompromised patients. Among the causal agents, Candida albicans is the dominant one. Various animal models have been developed for investigating gene functions in C. albicans. Zebrafish injection models have increasingly been applied in elucidating C. albicans pathogenesis because of the conserved immunity, prolific fecundity of the zebrafish and the low costs of care systems. In this study, we established a simple, noninvasive zebrafish egg bath infection model, defined its optimal conditions, and evaluated the model with various C. albicans mutant strains. The deletion of SAP6 did not have significant effect on the virulence. By contrast, the deletion of BCR1, CPH1, EFG1, or TEC1 significantly reduced the virulence under current conditions. Furthermore, all embryos survived when co-incubated with bcr1/bcr1, cph1/cph1 efg1/efg1, efg1/efg1, or tec1/tec1 mutant cells. The results indicated that our novel zebrafish model is time-saving and cost effective.

  7. Prevalence of non-albican candida infection in Maharashtrian women with leucorrhea

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    Seema M Bankar

    2012-01-01

    Full Text Available Background: Candida is the most common agent causing leucorrhea affecting the women of all strata. It is becoming difficult to completely eradicate the infection mainly due to recurrence caused by non-albican species of Candida. Most of the non-albican species of Candida are resistant to commonly used antifungal agent - azole. Therefore, studying the prevalence of Candida species in vaginal secretion is of great significance. Objective: To study the prevalence of different species of Candida and the efficiency of different Candida detection methods in women from low socio-economic setup of Miraj and Sangli, Maharashtra, India. Materials and Methods: The study was conducted on 150 patients with specific complaints of leucorrhea. In the control group, 50 asymptomatic women were included for comparison. Results: In 33% of the women the leucorrhea was due to Candida infection with highest incidence in women of sexually active age (20-40 years. Sabouraud′s culture was the most efficient method (100% efficiency to detect the Candida compared to wet mount, KOH and gram stain method. Candida albicans was the most common strain identified and Candida krusei was the least common one. Conclusion: Candida infection is the commonest reason for leucorrhea and non-albican candida species significantly contribute to candidiasis in women of Miraj and Sangli.

  8. Candida albicans interface infection after deep anterior lamellar keratoplasty

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    Mohammad Reza Sedaghat

    2012-01-01

    Full Text Available The clinical features of interface Candida keratitis after deep anterior lamellar keratoplasty (DALK, may imitate rejection or crystalline keratopathy. We report here an 18-year-old woman presented with red eye, 4 months after undergoing DALK. Slit lamp examination revealed keratic precipitates (KPs and cojunctival injection. She was prescribed corticosteroid treatment for endothelial rejection by another ophthalmologist because of misdiagnosis, but suffered a recurrence of symptoms after reduction of the corticosteroid treatment. At that time, she was referred to our office. The recurrence persisted despite antibiotic and antifungal therapies. Ten days after treatment with interface irrigation with amphotericin, the infiltration and hypopyon were resolved. Topical steroid was added after 3 months of antifungal monotherapy. Irrigant cultures confirmed the presence of Candida albicans. The corneal graft appeared semi-clear with no signs of infection at 17-month follow-up. We recommend a close follow-up and a timely intervention to prevent the need for more invasive treatment such as penetrating keratoplasty.

  9. Host defence against disseminated and invasive Candida albicans infections

    NARCIS (Netherlands)

    Vonk, Alouise Gabrielle

    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 disseminat

  10. Synthesis of Melanin Pigment by Candida albicans In Vitro and during Infection

    OpenAIRE

    Morris-Jones, Rachael; Gomez, Beatriz L.; Diez, Soraya; Uran, Martha; Morris-Jones, Stephen D.; Casadevall, Arturo; Nosanchuk, Joshua D.; Hamilton, Andrew J.

    2005-01-01

    Melanins are implicated in the pathogenesis of several important human diseases. This study confirmed the presence of melanin particles in Candida albicans in vitro and during infection. Dark particles were isolated from the digestion of C. albicans cultures and from infected tissue, as established by electron microscopy and immunofluorescence techniques.

  11. Systemic Staphylococcus aureus infection mediated by Candida albicans hyphal invasion of mucosal tissue

    NARCIS (Netherlands)

    L.M. Schlecht; B.M. Peters; B.P. Krom; J.A. Freiberg; G.M. Hänsch; S.G. Filler; M.A. Jabra-Rizk; M.E. Shirtliff

    2015-01-01

    Candida albicans and Staphylococcus aureus are often co-isolated in cases of biofilm-associated infections. C. albicans can cause systemic disease through morphological switch from the rounded yeast to the invasive hyphal form. Alternatively, systemic S. aureus infections arise from seeding through

  12. 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

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

    International Nuclear Information System (INIS)

    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 Ca2+–Mg2+ ATPase in C. albicans. • Baicalin increases the endocytic free Ca2+ 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 3H-UdR, 3H-TdR and 3H-leucine incorporation into C. albicans using the isotope incorporation technology. The activities of Succinate Dehydrogenase (SDH), cytochrome oxidase (CCO) and Ca2+–Mg2+ ATPase, cytosolic Ca2+ concentration, the cell cycle and apoptosis, as well as the ultrastructure of C.albicans were also tested. We found that baicalin inhibited 3H-UdR, 3H-TdR and 3H-leucine incorporation into C.albicans (P < 0.005). The activities of the SDH and Ca2+–Mg2+ ATPase of C.albicans in baicalin groups were lower than those in control group (P < 0.05). Ca2+ 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 Ca2+–Mg2+ ATPase, increasing cytosolic Ca2+ content and damaging the ultrastructure of C. albicans

  14. Humoral immunity links Candida albicans infection and celiac disease.

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    Marion Corouge

    Full Text Available The protein Hwp1, expressed on the pathogenic phase of Candida albicans, presents sequence analogy with the gluten protein gliadin and is also a substrate for transglutaminase. This had led to the suggestion that C. albicans infection (CI may be a triggering factor for Celiac disease (CeD onset. We investigated cross-immune reactivity between CeD and CI.Serum IgG levels against recombinant Hwp1 and serological markers of CeD were measured in 87 CeD patients, 41 CI patients, and 98 healthy controls (HC. IgA and IgG were also measured in 20 individuals from each of these groups using microchips sensitized with 38 peptides designed from the N-terminal of Hwp1.CI and CeD patients had higher levels of anti-Hwp1 (p=0.0005 and p=0.004 and anti-gliadin (p=0.002 and p=0.0009 antibodies than HC but there was no significant difference between CeD and CI patients. CeD and CI patients had higher levels of anti-transglutaminase IgA than HC (p=0.0001 and p=0.0039. During CI, the increase in anti-Hwp1 paralleled the increase in anti-gliadin antibodies. Microchip analysis showed that CeD patients were more reactive against some Hwp1 peptides than CI patients, and that some deamidated peptides were more reactive than their native analogs. Binding of IgG from CeD patients to Hwp1 peptides was inhibited by γIII gliadin peptides.Humoral cross-reactivity between Hwp1 and gliadin was observed during CeD and CI. Increased reactivity to Hwp1 deamidated peptide suggests that transglutaminase is involved in this interplay. These results support the hypothesis that CI may trigger CeD onset in genetically-susceptible individuals.

  15. Humoral Immunity Links Candida albicans Infection and Celiac Disease

    Science.gov (United States)

    Fradin, Chantal; Salleron, Julia; Damiens, Sébastien; Moragues, Maria Dolores; Souplet, Vianney; Jouault, Thierry; Robert, Raymond; Dubucquoi, Sylvain; Sendid, Boualem; Colombel, Jean Fréderic; Poulain, Daniel

    2015-01-01

    Objective The protein Hwp1, expressed on the pathogenic phase of Candida albicans, presents sequence analogy with the gluten protein gliadin and is also a substrate for transglutaminase. This had led to the suggestion that C. albicans infection (CI) may be a triggering factor for Celiac disease (CeD) onset. We investigated cross-immune reactivity between CeD and CI. Methods Serum IgG levels against recombinant Hwp1 and serological markers of CeD were measured in 87 CeD patients, 41 CI patients, and 98 healthy controls (HC). IgA and IgG were also measured in 20 individuals from each of these groups using microchips sensitized with 38 peptides designed from the N-terminal of Hwp1. Results CI and CeD patients had higher levels of anti-Hwp1 (p=0.0005 and p=0.004) and anti-gliadin (p=0.002 and p=0.0009) antibodies than HC but there was no significant difference between CeD and CI patients. CeD and CI patients had higher levels of anti-transglutaminase IgA than HC (p=0.0001 and p=0.0039). During CI, the increase in anti-Hwp1 paralleled the increase in anti-gliadin antibodies. Microchip analysis showed that CeD patients were more reactive against some Hwp1 peptides than CI patients, and that some deamidated peptides were more reactive than their native analogs. Binding of IgG from CeD patients to Hwp1 peptides was inhibited by γIII gliadin peptides. Conclusions Humoral cross-reactivity between Hwp1 and gliadin was observed during CeD and CI. Increased reactivity to Hwp1 deamidated peptide suggests that transglutaminase is involved in this interplay. These results support the hypothesis that CI may trigger CeD onset in genetically-susceptible individuals. PMID:25793717

  16. Th17 cells confer long term adaptive immunity to oral mucosal Candida albicans infections

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    Hernández-Santos, Nydiaris; Huppler, Anna R; Peterson, Alanna C.; Khader, Shabaana A.; McKenna, Kyle C.; Sarah L Gaffen

    2012-01-01

    Oropharyngeal candidiasis (OPC) is an opportunistic infection caused by Candida albicans. Despite its prevalence, little is known about C. albicans-specific immunity in the oral mucosa. Vaccines against Candida generate both Th1 and Th17 responses, and considerable evidence implicates IL-17 in immunity to OPC. However, IL-17 is also produced by innate immune cells that are remarkably similar to Th17 cells, expressing the same markers and localizing to similar mucosal sites. To date, the relat...

  17. Intra-amniotic Candida albicans infection induces mucosal injury and inflammation in the ovine fetal intestine.

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    Nikiforou, Maria; Jacobs, Esmee M R; Kemp, Matthew W; Hornef, Mathias W; Payne, Matthew S; Saito, Masatoshi; Newnham, John P; Janssen, Leon E W; Jobe, Alan H; Kallapur, Suhas G; Kramer, Boris W; Wolfs, Tim G A M

    2016-01-01

    Chorioamnionitis is caused by intrauterine infection with microorganisms including Candida albicans (C.albicans). Chorioamnionitis is associated with postnatal intestinal pathologies including necrotizing enterocolitis. The underlying mechanisms by which intra-amniotic C.albicans infection adversely affects the fetal gut remain unknown. Therefore, we assessed whether intra-amniotic C.albicans infection would cause intestinal inflammation and mucosal injury in an ovine model. Additionally, we tested whether treatment with the fungistatic fluconazole ameliorated the adverse intestinal outcome of intra-amniotic C.albicans infection. Pregnant sheep received intra-amniotic injections with 10(7) colony-forming units C.albicans or saline at 3 or 5 days before preterm delivery at 122 days of gestation. Fetuses were given intra-amniotic and intra-peritoneal fluconazole treatments 2 days after intra-amniotic administration of C.albicans. Intra-amniotic C.albicans caused intestinal colonization and invasive growth within the fetal gut with mucosal injury and intestinal inflammation, characterized by increased CD3(+) lymphocytes, MPO(+) cells and elevated TNF-α and IL-17 mRNA levels. Fluconazole treatment in utero decreased intestinal C.albicans colonization, mucosal injury but failed to attenuate intestinal inflammation. Intra-amniotic C.albicans caused intestinal infection, injury and inflammation. Fluconazole treatment decreased mucosal injury but failed to ameliorate C.albicans-mediated mucosal inflammation emphasizing the need to optimize the applied antifungal therapeutic strategy. PMID:27411776

  18. Imaging morphogenesis of Candida albicans during infection in a live animal

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    Mitra, Soumya; Dolan, Kristy; Foster, Thomas H.; Wellington, Melanie

    2010-01-01

    Candida albicans is an opportunistic human fungal pathogen that requires an intact host immune response to prevent disease. Thus, studying host-pathogen interactions is critical to understanding and preventing this disease. We report a new model infection system in which ongoing C. albicans infections can be imaged at high spatial resolution in the ears of living mice. Intradermal inoculation into mouse ears with a C. albicans strain expressing green fluorescent protein results in systemic C. albicans infection that can be imaged in vivo using confocal microscopy. We observed filamentous growth of the organism in vivo as well as formation of microabscesses. This model system will allow us to gain significant new information about C. albicans pathogenesis through studies of host-C. albicans interactions in the native environment.

  19. Antimicrobial blue light therapy for Candida albicans burn infection in mice

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    Zhang, Yunsong; Wang, Yucheng; Murray, Clinton K.; Hamblin, Michael R.; Gu, Ying; Dai, Tianhong

    2015-05-01

    In this preclinical study, we investigated the utility of antimicrobial blue light therapy for Candida albicans infection in acutely burned mice. A bioluminescent strain of C. albicans was used. The susceptibilities to blue light inactivation were compared between C. albicans and human keratinocyte. In vitro serial passaging of C. albicans on blue light exposure was performed to evaluate the potential development of resistance to blue light inactivation. A mouse model of acute thermal burn injury infected with the bioluminescent strain of C. albicans was developed. Blue light (415 nm) was delivered to mouse burns for decolonization of C. albicans. Bioluminescence imaging was used to monitor in real time the extent of fungal infection in mouse burns. Experimental results showed that C. albicans was approximately 42-fold more susceptible to blue light inactivation in vitro than human keratinocyte (P=0.0022). Serial passaging of C. albicans on blue light exposure implied a tendency for the fungal susceptibility to blue light inactivation to decrease with the numbers of passages. Blue light reduced fungal burden by over 4-log10 (99.99%) in acute mouse burns infected with C. albicans in comparison to infected mouse burns without blue light therapy (P=0.015).

  20. 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.

  1. Investigation of minor species Candida africana, Candida stellatoidea and Candida dubliniensis in the Candida albicans complex among Yaoundé (Cameroon) HIV-infected patients.

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    Ngouana, Thierry K; Krasteva, Donika; Drakulovski, Pascal; Toghueo, Rufin K; Kouanfack, Charles; Ambe, Akaba; Reynes, Jacques; Delaporte, Eric; Boyom, Fabrice F; Mallié, Michèle; Bertout, Sébastien

    2015-01-01

    Minor species of the Candida albicans complex may cause overestimation of the epidemiology of C. albicans, and misidentifications could mask their implication in human pathology. Authors determined the occurrence of minor species of the C. albicans complex (C. africana, C. dubliniensis and C. stellatoidea) among Yaoundé HIV-infected patients, Cameroon. Stool, vaginal discharge, urine and oropharyngeal samples were analysed by mycological diagnosis. Isolates were identified by conventional methods and mass spectrometry (MS; carried out by the matrix-assisted laser desorption-ionisation time-of-flight MS protocol). Candida albicans isolates were thereafter submitted to the PCR amplification of the Hwp1 gene. The susceptibility of isolates to antifungal drugs was tested using the Clinical and Laboratory Standards Institute M27-A3 protocol. From 115 C. albicans obtained isolates, neither C. dubliniensis nor C. stellatoidea was observed; two strains of C. africana (422PV and 448PV) were identified by PCR electrophoretic profiles at 700 bp. These two C. africana strains were vaginal isolates. The isolate 448PV was resistant to ketoconazole at the minimal inhibitory concentration of 2 μg ml(-1), and showed reduced susceptibility to amphotericin B at 1 μg ml(-1). This first report on C. africana occurrence in Cameroon brings clues for the understanding of the global epidemiology of this yeast as well as that of minor species of the C. albicans complex.

  2. Association of KPC-producing Klebsiella pneumoniae colonization or infection with Candida isolation and selection of non-albicans species.

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    Papadimitriou-Olivgeris, Matthaios; Spiliopoulou, Anastasia; Fligou, Fotini; Manolopoulou, Patroula; Spiliopoulou, Iris; Vrettos, Theofanis; Dodou, Vasiliki; Filos, Kriton S; Anastassiou, Evangelos D; Marangos, Markos; Christofidou, Myrto

    2014-11-01

    Clinical specimens from 565 patients hospitalized in 2 intensive care units (ICUs A and B) during a 28-month period were cultured on appropriate media for isolation of Candida. Forty-nine (9%) patients had at least a Candida spp.-positive sample. Candida albicans was the predominant species isolated from 26 (53%) patients. Seventeen patients (3%) developed candidemia. Multivariate analysis showed that obesity, female gender, hospitalization during summer months, admission at ICU B, parenteral nutrition, administration of metronidazole, transplantation, and KPC-producing Klebsiella pneumoniae (KPC-Kp) infection were independently associated with Candida spp. isolation. Candidemia was associated with cortisone administration, KPC-Kp infection, and presence of colostomy or abdominal catheter. Administration of fluconazole was a protective factor for both Candida spp. isolation and infection, leading to selection of Candida non-albicans species. Among several risk factors, KPC-Kp infection and colonization are identified as statistically significant factors associated with Candida isolation, especially of non-albicans species.

  3. Analysis of genital Candida albicans infection by rapid microsatellite markers genotyping

    Institute of Scientific and Technical Information of China (English)

    SHI Wei-min; MEI Xing-yu; GAO Fei; HUO Ke-ke; SHEN Liang-liang; QIN Hai-hong; WU Zhou-wei; ZHENG Jie

    2007-01-01

    Background Candida albicans (C. albicans) infection, often occurring in genital candidiasis, has increased dramatically recently. Developing an efficient C. albicans typing method may contribute to understanding its epidemiological characteristics and guiding efficient treatment. We used rapid microsatellite genotyping assay for interstrain differentiation of C. albicans isolates and explored some characteristics of its spread.Methods DNA was extracted from C. albicans isolates from gentalia, recta and mouths of 39 female cases and 27 male cases of genital candidiasis. Three fluorescent primers for the microsatellite markers in conserved genes (CDC3, EF3and HIS3) of C. albicans were used to amplify the isolates DNA by PCR. Fluorescent signals were read with an automatic sequencer and analyzed with GeneScan software.Results Analysis of the three microsatellites markers showed 18 gene allelic associations in genital C. albicans infected patients: 10 allelic associations in female and 11 allelic associations in male, of which 3 allelic associations shared by both genders covered 71% of infections. The most dominant allele association of pathogenic strains for both genders was 116:124, 122:131,160:200 that covered about 50% of infection. Gentalia and recta shared the same strains in 80%of female patients, but in only 3.8% of male patients. There were 2.7% female patients, but no males, with same strain in both gentalia and mouths. Five of seven genital C. albicans infected couples had the same allelic associations of which 4were the dominant pathogenic C. albicans susceptible for both genders.Conclusions The predominant allelic association of the pathogenic strain in genital C. albicans infection is 116:124,122:131, 160:200. Vaginal pathogenic strains are probably maintained from the rectal reservoir. Pathogenic strains of male patients are probably from frequent sexual intercourse. The aggressiveness of some strains varies with gender.

  4. 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.

  5. 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.

  6. Analysis of the relationship between fluconazole consumption and non-C. albicans Candida infections.

    Science.gov (United States)

    Tyczkowska-Sieron, E; Gaszynski, W; Tyczkowski, J; Glowacka, A

    2014-10-01

    The effect of fluconazole consumption on the incidence of nosocomial non-C. albicans Candida infections remains unclear. In this study we investigated such a relationship in an intensive care unit (Poland) over an 11-year period (2002-2012). Statistics relating to the number of candidiasis cases and the number of defined daily doses of fluconazole showed that only a very weak and not statistically significant linear correlation existed between these two variables (r(2) = 0.36, P = 0.052). However, the assumption of a 1-year delay in the infection response to changes in fluconazole concentrations resulted in a strong and statistically significant linear correlation (r(2) = 0.64, P = 0.0053). To more accurately determine the nature of this relationship, a simple epidemiological model was proposed that provided a better than linear correlation (r(2) = 0.78, P = 0.00077). We successfully used this approach to analyze results from the literature that were interpreted as evidence that fluconazole use is not a risk factor for development of non-C. albicans Candida infections. If a time delay in the infection response was assumed, a strong and statistically significant correlation was obtained. These findings suggest the need for a closer look at fluconazole therapy as a possible risk factor for development of non-C. albicans Candida infections.

  7. Mixed Fungal Lung Infection with Aspergillus Fumigatus and Candida Albicans in a Immunocomprimised Patient: Case Report

    OpenAIRE

    S., Jaya; Vipparti, Haritha

    2014-01-01

    The frequency of invasive, opportunistic mycoses has increased significantly over the past 2 decades. In the immune-compromised host, many fungi, including species of fungi typically considered non-pathogenic, have the potential to cause serious morbidity and mortality. Here we report a rare case of mixed fungal infection of the lung with Candida albicans and Aspergillus fumigatus in a patient on prolonged steroid therapy.

  8. 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

  9. Skin Immunity to Candida albicans.

    Science.gov (United States)

    Kashem, Sakeen W; Kaplan, Daniel H

    2016-07-01

    Candida albicans is a dimorphic commensal fungus that colonizes healthy human skin, mucosa, and the reproductive tract. C. albicans is also a predominantly opportunistic fungal pathogen, leading to disease manifestations such as disseminated candidiasis and chronic mucocutaneous candidiasis (CMC). The differing host susceptibilities for the sites of C. albicans infection have revealed tissue compartmentalization with tailoring of immune responses based on the site of infection. Furthermore, extensive studies of host genetics in rare cases of CMC have identified conserved genetic pathways involved in immune recognition and the response to the extracellular pathogen. We focus here on human and mouse skin as a site of C. albicans infection, and we review established and newly discovered insights into the cellular pathways that promote cutaneous antifungal immunity. PMID:27178391

  10. Candida albicans skin abscess Abscesso de pele por Candida albicans

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    Felipe Francisco Tuon

    2006-10-01

    Full Text Available Subcutaneous candidal abscess is a very rare infection even in immunocompromised patients. Some cases are reported when breakdown in the skin occurs, as bacterial cellulites or abscess, iatrogenic procedures, trauma and parenteral substance abuse. We describe a case of Candida albicans subcutaneous abscess without fungemia, which can be associated with central venous catheter.Abscesso subcutâneo por Candida é infecção muito rara mesmo em pacientes imunocomprometidos. Alguns casos são relatados quando ocorre dano na pele, como celulite bacteriana ou abscesso, procedimentos iatrogênicos, trauma e abuso de substância parenteral. Relatamos caso de abscesso subcutâneo por Candida albicans sem fungemia, que pode estar associado com cateter venoso central.

  11. IL-12 and Related Cytokines: Function and Regulatory Implications in Candida albicans Infection

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    Robert B. Ashman

    2011-01-01

    Full Text Available IL-12 is a cytokine with links to both innate and adaptive immunity systems. In mice, its deletion leads to acute susceptibility to oral infection with the yeast Candida albicans, whereas such mice are resistant to systemic disease. However, it is an essential component of the adaptive response that leads to the generation of Th1-type cytokine responses and protection against disseminated disease. This paper presents an overview of the role of IL-12 in models of systemic and mucosal infection and the possible relationships between them.

  12. Th17 cells confer long-term adaptive immunity to oral mucosal Candida albicans infections.

    Science.gov (United States)

    Hernández-Santos, N; Huppler, A R; Peterson, A C; Khader, S A; McKenna, K C; Gaffen, S L

    2013-09-01

    Oropharyngeal candidiasis (OPC) is an opportunistic infection caused by Candida albicans. Despite its prevalence, little is known about C. albicans-specific immunity in the oral mucosa. Vaccines against Candida generate both T helper type 1 (Th1) and Th17 responses, and considerable evidence implicates interleukin (IL)-17 in immunity to OPC. However, IL-17 is also produced by innate immune cells that are remarkably similar to Th17 cells, expressing the same markers and localizing to similar mucosal sites. To date, the relative contribution(s) of Th1, Th17, and innate IL-17-producing cells in OPC have not been clearly defined. Here, we sought to determine the nature and function of adaptive T-cell responses to OPC, using a new recall infection model. Mice subjected to infection and re-challenge with Candida mounted a robust and stable antigen-specific IL-17 response in CD4+ but not CD8+ T cells. There was little evidence for Th1 or Th1/Th17 responses. The Th17 response promoted accelerated fungal clearance, and Th17 cells could confer protection in Rag1-/- mice upon adoptive transfer. Surprisingly, CD4 deficiency did not cause OPC but was instead associated with compensatory IL-17 production by Tc17 and CD3+CD4-CD8- cells. Therefore, classic CD4+Th17 cells protect from OPC but can be compensated by other IL-17-producing cells in CD4-deficient hosts. PMID:23250275

  13. Divergent responses of different endothelial cell types to infection with Candida albicans and Staphylococcus aureus.

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    Kati Seidl

    Full Text Available Endothelial cells are important in the pathogenesis of bloodstream infections caused by Candida albicans and Staphylococcus aureus. Numerous investigations have used human umbilical vein endothelial cells (HUVECs to study microbial-endothelial cell interactions in vitro. However, the use of HUVECs requires a constant supply of umbilical cords, and there are significant donor-to-donor variations in these endothelial cells. The use of an immortalized endothelial cell line would obviate such difficulties. One candidate in this regard is HMEC-1, an immortalized human dermal microvascular endothelial cell line. To determine if HMEC-1 cells are suitable for studying the interactions of C. albicans and S. aureus with endothelial cells in vitro, we compared the interactions of these organisms with HMEC-1 cells and HUVECs. We found that wild-type C. albicans had significantly reduced adherence to and invasion of HMEC-1 cells as compared to HUVECs. Although wild-type S. aureus adhered to and invaded HMEC-1 cells similarly to HUVECs, an agr mutant strain had significantly reduced invasion of HMEC-1 cells, but not HUVECs. Furthermore, HMEC-1 cells were less susceptible to damage induced by C. albicans, but more susceptible to damage caused by S. aureus. In addition, HMEC-1 cells secreted very little IL-8 in response to infection with either organism, whereas infection of HUVECs induced substantial IL-8 secretion. This weak IL-8 response was likely due to the anatomic site from which HMEC-1 cells were obtained because infection of primary human dermal microvascular endothelial cells with C. albicans and S. aureus also induced little increase in IL-8 production above basal levels. Thus, C. albicans and S. aureus interact with HMEC-1 cells in a substantially different manner than with HUVECs, and data obtained with one type of endothelial cell cannot necessarily be extrapolated to other types.

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

    Science.gov (United States)

    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.

  15. Acetylcholine Protects against Candida albicans Infection by Inhibiting Biofilm Formation and Promoting Hemocyte Function in a Galleria mellonella Infection Model.

    Science.gov (United States)

    Rajendran, Ranjith; Borghi, Elisa; Falleni, Monica; Perdoni, Federica; Tosi, Delfina; Lappin, David F; O'Donnell, Lindsay; Greetham, Darren; Ramage, Gordon; Nile, Christopher

    2015-08-01

    Both neuronal acetylcholine and nonneuronal acetylcholine have been demonstrated to modulate inflammatory responses. Studies investigating the role of acetylcholine in the pathogenesis of bacterial infections have revealed contradictory findings with regard to disease outcome. At present, the role of acetylcholine in the pathogenesis of fungal infections is unknown. Therefore, the aim of this study was to determine whether acetylcholine plays a role in fungal biofilm formation and the pathogenesis of Candida albicans infection. The effect of acetylcholine on C. albicans biofilm formation and metabolism in vitro was assessed using a crystal violet assay and phenotypic microarray analysis. Its effect on the outcome of a C. albicans infection, fungal burden, and biofilm formation were investigated in vivo using a Galleria mellonella infection model. In addition, its effect on modulation of host immunity to C. albicans infection was also determined in vivo using hemocyte counts, cytospin analysis, larval histology, lysozyme assays, hemolytic assays, and real-time PCR. Acetylcholine was shown to have the ability to inhibit C. albicans biofilm formation in vitro and in vivo. In addition, acetylcholine protected G. mellonella larvae from C. albicans infection mortality. The in vivo protection occurred through acetylcholine enhancing the function of hemocytes while at the same time inhibiting C. albicans biofilm formation. Furthermore, acetylcholine also inhibited inflammation-induced damage to internal organs. This is the first demonstration of a role for acetylcholine in protection against fungal infections, in addition to being the first report that this molecule can inhibit C. albicans biofilm formation. Therefore, acetylcholine has the capacity to modulate complex host-fungal interactions and plays a role in dictating the pathogenesis of fungal infections.

  16. Modulation of macrophage cytokine profiles during solid tumor progression: susceptibility to Candida albicans infection

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    Venturini James

    2009-06-01

    Full Text Available Abstract Background In order to attain a better understanding of the interactions between opportunist fungi and their hosts, we investigated the cytokine profile associated with the inflammatory response to Candida albicans infection in mice with solid Ehrlich tumors of different degrees. Methods Groups of eight animals were inoculated intraperitoneally with 5 × 106 C. albicans 7, 14 or 21 days after tumor implantation. After 24 or 72 hours, the animals were euthanized and intraperitoneal lavage fluid was collected. Peritoneal macrophages were cultivated and the levels of IFN-γ, TNF-α, IL-12, IL-10 and IL-4 released into the supernatants were measured by ELISA. Kidney, liver and spleen samples were evaluated for fungal dissemination. Tumor-free animals and animals that had only been subjected to C. albicans infection were used as control groups. Results Our results demonstrated that the mice produced more IFN-γ and TNF-α and less IL-10, and also exhibited fungal clearance, at the beginning of tumor evolution. With the tumor progression, this picture changed: IL-10 production increased and IFN-γ and TNF-α release decreased; furthermore, there was extensive fungal dissemination. Conclusion Our results indicate that solid tumors can affect the production of macrophage cytokines and, in consequence, affect host resistance to opportunistic infections.

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

    Science.gov (United States)

    Whibley, Natasha; Gaffen, Sarah L

    2015-11-01

    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 Candida 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.

  18. 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.

  19. Autophagy is redundant for the host defense against systemic Candida albicans infections

    NARCIS (Netherlands)

    Smeekens, S.P.; Malireddi, R.K.; Plantinga, T.S.; Buffen, K.; Oosting, M.; Joosten, L.A.B.; Kullberg, B.J.; Perfect, J.R.; Scott, W.K.; Veerdonk, F.L. van de; Xavier, R.J.; Vosse, E. van de; Kanneganti, T.D.; Johnson, M.D.; Netea, M.G.

    2014-01-01

    Autophagy has been demonstrated to play an important role in the immunity against intracellular pathogens, but very little is known about its role in the host defense against fungal pathogens such as Candida albicans. Therefore, the role of autophagy for the host defense against C. albicans was asse

  20. 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. PMID:25009452

  1. Commensal enteric bacteria lipopolysaccharide impairs host defense against disseminated Candida albicans fungal infection.

    Science.gov (United States)

    Jiang, T T; Chaturvedi, V; Ertelt, J M; Xin, L; Clark, D R; Kinder, J M; Way, S S

    2015-07-01

    Commensal enteric bacteria maintain systemic immune responsiveness that protects against disseminated or localized infection in extra-intestinal tissues caused by pathogenic microbes. However, as shifts in infection susceptibility after commensal bacteria eradication have primarily been probed using viruses, the broader applicability to other pathogen types remains undefined. In sharp contrast to diminished antiviral immunity, we show commensal bacteria eradication bolsters protection against disseminated Candida albicans fungal infection. Enhanced antifungal immunity reflects more robust systemic expansion of Ly6G(hi)Ly6C(int) neutrophils, and their mobilization into infected tissues among antibiotic-treated compared with commensal bacteria-replete control mice. Reciprocally, depletion of neutrophils from expanded levels or intestinal lipopolysaccharide reconstitution overrides the antifungal protective benefits conferred by commensal bacteria eradication. This discordance in antifungal compared with antiviral immunity highlights intrinsic differences in how commensal bacteria control responsiveness for specific immune cell subsets, because pathogen-specific CD8(+) T cells that protect against viruses were suppressed similarly after C. albicans and influenza A virus infection. Thus, positive calibration of antiviral immunity by commensal bacteria is counterbalanced by restrained activation of other immune components that confer antifungal immunity.

  2. 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.

  3. Host-Imposed Copper Poisoning Impacts Fungal Micronutrient Acquisition during Systemic Candida albicans Infections.

    Science.gov (United States)

    Mackie, Joanna; Szabo, Edina K; Urgast, Dagmar S; Ballou, Elizabeth R; Childers, Delma S; MacCallum, Donna M; Feldmann, Joerg; Brown, Alistair J P

    2016-01-01

    Nutritional immunity is a process whereby an infected host manipulates essential micronutrients to defend against an invading pathogen. We reveal a dynamic aspect of nutritional immunity during infection that involves copper assimilation. Using a combination of laser ablation inductively coupled mass spectrometry (LA-ICP MS) and metal mapping, immunohistochemistry, and gene expression profiling from infected tissues, we show that readjustments in hepatic, splenic and renal copper homeostasis accompany disseminated Candida albicans infections in the mouse model. Localized host-imposed copper poisoning manifests itself as a transient increase in copper early in the kidney infection. Changes in renal copper are detected by the fungus, as revealed by gene expression profiling and fungal virulence studies. The fungus responds by differentially regulating the Crp1 copper efflux pump (higher expression during early infection and down-regulation late in infection) and the Ctr1 copper importer (lower expression during early infection, and subsequent up-regulation late in infection) to maintain copper homeostasis during disease progression. Both Crp1 and Ctr1 are required for full fungal virulence. Importantly, copper homeostasis influences other virulence traits-metabolic flexibility and oxidative stress resistance. Our study highlights the importance of copper homeostasis for host defence and fungal virulence during systemic disease. PMID:27362522

  4. Host-Imposed Copper Poisoning Impacts Fungal Micronutrient Acquisition during Systemic Candida albicans Infections.

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    Joanna Mackie

    Full Text Available Nutritional immunity is a process whereby an infected host manipulates essential micronutrients to defend against an invading pathogen. We reveal a dynamic aspect of nutritional immunity during infection that involves copper assimilation. Using a combination of laser ablation inductively coupled mass spectrometry (LA-ICP MS and metal mapping, immunohistochemistry, and gene expression profiling from infected tissues, we show that readjustments in hepatic, splenic and renal copper homeostasis accompany disseminated Candida albicans infections in the mouse model. Localized host-imposed copper poisoning manifests itself as a transient increase in copper early in the kidney infection. Changes in renal copper are detected by the fungus, as revealed by gene expression profiling and fungal virulence studies. The fungus responds by differentially regulating the Crp1 copper efflux pump (higher expression during early infection and down-regulation late in infection and the Ctr1 copper importer (lower expression during early infection, and subsequent up-regulation late in infection to maintain copper homeostasis during disease progression. Both Crp1 and Ctr1 are required for full fungal virulence. Importantly, copper homeostasis influences other virulence traits-metabolic flexibility and oxidative stress resistance. Our study highlights the importance of copper homeostasis for host defence and fungal virulence during systemic disease.

  5. Host-Imposed Copper Poisoning Impacts Fungal Micronutrient Acquisition during Systemic Candida albicans Infections

    Science.gov (United States)

    Mackie, Joanna; Ballou, Elizabeth R.; Childers, Delma S.; MacCallum, Donna M.; Feldmann, Joerg; Brown, Alistair J. P.

    2016-01-01

    Nutritional immunity is a process whereby an infected host manipulates essential micronutrients to defend against an invading pathogen. We reveal a dynamic aspect of nutritional immunity during infection that involves copper assimilation. Using a combination of laser ablation inductively coupled mass spectrometry (LA-ICP MS) and metal mapping, immunohistochemistry, and gene expression profiling from infected tissues, we show that readjustments in hepatic, splenic and renal copper homeostasis accompany disseminated Candida albicans infections in the mouse model. Localized host-imposed copper poisoning manifests itself as a transient increase in copper early in the kidney infection. Changes in renal copper are detected by the fungus, as revealed by gene expression profiling and fungal virulence studies. The fungus responds by differentially regulating the Crp1 copper efflux pump (higher expression during early infection and down-regulation late in infection) and the Ctr1 copper importer (lower expression during early infection, and subsequent up-regulation late in infection) to maintain copper homeostasis during disease progression. Both Crp1 and Ctr1 are required for full fungal virulence. Importantly, copper homeostasis influences other virulence traits—metabolic flexibility and oxidative stress resistance. Our study highlights the importance of copper homeostasis for host defence and fungal virulence during systemic disease. PMID:27362522

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

    International Nuclear Information System (INIS)

    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)

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  8. Candida albicans OPI1 regulates filamentous growth and virulence in vaginal infections, but not inositol biosynthesis.

    Directory of Open Access Journals (Sweden)

    Ying-Lien Chen

    Full Text Available ScOpi1p is a well-characterized transcriptional repressor and master regulator of inositol and phospholipid biosynthetic genes in the baker's yeast Saccharomyces cerevisiae. An ortholog has been shown to perform a similar function in the pathogenic fungus Candida glabrata, but with the distinction that CgOpi1p is essential for growth in this organism. However, in the more distantly related yeast Yarrowia lipolytica, the OPI1 homolog was not found to regulate inositol biosynthesis, but alkane oxidation. In Candida albicans, the most common cause of human candidiasis, its Opi1p homolog, CaOpi1p, has been shown to complement a S. cerevisiae opi1∆ mutant for inositol biosynthesis regulation when heterologously expressed, suggesting it might serve a similar role in this pathogen. This was tested in the pathogen directly in this report by disrupting the OPI1 homolog and examining its phenotypes. It was discovered that the OPI1 homolog does not regulate INO1 expression in C. albicans, but it does control SAP2 expression in response to bovine serum albumin containing media. Meanwhile, we found that CaOpi1 represses filamentous growth at lower temperatures (30 °C on agar, but not in liquid media. Although, the mutant does not affect virulence in a mouse model of systemic infection, it does affect virulence in a rat model of vaginitis. This may be because Opi1p regulates expression of the SAP2 protease, which is required for rat vaginal infections.

  9. A new model of vaginal infection by Candida albicans in rats.

    Science.gov (United States)

    Carrara, Márcia A; Donatti, Lucélia; Damke, Edílson; Svidizinski, Terezinha I E; Consolaro, Márcia E L; Batista, Márcia R

    2010-11-01

    Vulvovaginal candidiasis (VVC) is regarded as an important public health issue, and several aspects of its pathogenesis are not yet sufficiently clear. Experimental in vivo models of vaginal infection with Candida albicans have been extremely useful in the identification of factors concerning hormonal influences on the infection, the virulence of the yeasts, the susceptibility, and the treatment of the infection. The development of easily manageable, reproducible, and economically viable animal models of VVC is highly important. We describe a simple experimental model of VVC in rats, using a pharmaceutical brand of estradiol hexa-hydrobenzoate for human treatment. All the steps of this model were standardized; and after the experiments, the rats were euthanized for further examination of their tissues by scanning and transmission electron microscopy. Standardized features included the use of non-ovariectomized rats, sterile distilled water as the hormone vehicle, estradiol hexa-hydrobenzoate administered at 0.20 mg/week/rat fractionated three times/week, and a yeast suspension of 5 × 10(8) yeasts/ml in a single vaginal administration 1 week after hormone induction. In this way, 100% of the rats were in pseudo-estrus and developed and maintained the infection until the third week of the experiment. Electron microscopy observation of the vagina of the rats confirmed the presence of both pseudo-estrus and vaginal infection. The standardized experimental model proved inexpensive, reproducible, and easily feasible for the induction of vaginal infection with C. albicans and may help to clarify important aspects of the pathogenesis and treatment of VVC.

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

    International Nuclear Information System (INIS)

    The aim of this study was to investigate whether technetium-99m labelled fluconazole can distinguish fungal from bacterial infections. Fluconazole was labelled with 99mTc 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 99mTc. 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 99mTc-fluconazole and 99mTc-labelled peptides/IgG at affected sites was determined scintigraphically. 99mTc-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 99mTc-fluconazole (T/NT ratio=3.1±0.2). A good correlation (R2=0.864; P99mTc-UBI 29-41 and 99mTc-hLF 1-11 were able to distinguish C. albicans infections from sterile inflammatory processes in mice, these 99mTc-labelled peptides did not distinguish these fungal infections from bacterial infections. It is concluded that 99mTc-fluconazole distinguishes infections with C. albicans from bacterial infections and sterile inflammations. (orig.)

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

    Directory of Open Access Journals (Sweden)

    Fengliang Liu

    2016-06-01

    Full Text Available 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.

  12. Epidemiology of Candida infection. II. Application of biochemical methods for typing of Candida albicans strains.

    Science.gov (United States)

    Budak, A

    1990-01-01

    Biochemical profiles of 350 C. albicans isolates from five towns in Poland and from Freiburg in Germany were determined on the basis of nine biochemical tests of Odds and Abbott method. API 20 C AUX system and additionally a resistogram. The analysis of the strains according to Odds' and Abbotts's system showed that investigated strains can be typed into 9 profile codes of common biochemical patterns. There were some differences among the profiles according to their geographical origin and anatomical sources of the isolation. On the basis of the ability C. albicans strains to assimilate of carbon sources, 350 isolates were categorised into 13 separate auxotrophic profiles with the major one: 2,576,174 accounting for 81% of the total. The majority of the investigated isolates were susceptible to antifungal agents (83%). A disproportionate distribution of auxotrophic profiles limited the use of resistogram method and API 20 C AUX as systems for typing C. albicans strains. On the other hand, the method of Odds and Abbott provides valuable criteria for typing of C. albicans. PMID:2130802

  13. 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 (PALCA, ACCA, 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.

  14. Elimination of Bloodstream Infections Associated with Candida albicans Biofilm in Intravascular Catheters

    Directory of Open Access Journals (Sweden)

    Freshta Akbari

    2015-06-01

    Full Text Available Intravascular catheters are among the most commonly inserted medical devices and they are known to cause a large number of catheter related bloodstream infections (BSIs. Biofilms are associated with many chronic infections due to the aggregation of microorganisms. One of these organisms is the fungus Candida albicans. It has shown to be one of the leading causes of catheter-related BSIs. The presence of biofilm on intravascular catheters provide increased tolerance against antimicrobial treatments, thus alternative treatment strategies are sought. Traditionally, many strategies, such as application of combined antimicrobials, addition of antifungals, and removal of catheters, have been practiced, but they were not successful in eradicating BSIs. Since these fungal infections can result in significant morbidity, mortality, and increased healthcare cost, other promising preventive strategies, including antimicrobial lock therapy, chelating agents, alcohol, and biofilm disruptors, have been applied. In this review, current success and failure of these new approaches, and a comparison with the previous strategies are discussed in order to understand which preventative treatment is the most effective in controlling the catheter-related BSIs.

  15. Proteolytic activity and cytokine up-regulation by non-albicans Candida albicans.

    Science.gov (United States)

    Nawaz, Ali; Pärnänen, Pirjo; Kari, Kirsti; Meurman, Jukka H

    2015-05-01

    Mouth is an important source of infections and oral infections such as Candida infections increase the risk of mortality. Our purpose was to investigate differences in proteolytic activity of non-albicans Candida albicans (non-albicans Candida) between clinical isolates and laboratory samples. The second aim was to assess the concentration of pro- and anti-inflammatory cytokine levels IL-1β, IL-10, and TNF-α in saliva of patients with the non-albicans Candida and Candida-negative saliva samples. Clinical yeast samples from our laboratory were used for analyses. Candida strains were grown in YPG at 37 °C for 24 h in water bath with shaking. The activity of Candida proteinases of cell and cell-free fractions were analyzed by MDPF-gelatin zymography. The levels of IL-1β, IL-10, and TNF-α were measured from saliva with ELISA. The study showed differences in the proteolytic activity among the non-albicans Candida strains. C. tropicalis had higher proteolytic activity when compared to the other strains. Significant difference was found in salivary IL-1β levels between the non-albicans Candida and control strains (P albicans Candida strains. The increased IL-1β concentration may be one of the host response components associated with non-albicans Candida infection.

  16. 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...

  17. Differential association of fluconazole dose and dose/MIC ratio with mortality in patients with Candida albicans and non-albicans bloodstream infection.

    Science.gov (United States)

    Brosh-Nissimov, T; Ben-Ami, R

    2015-11-01

    Targeting fluconazole therapy to achieve predefined pharmacodynamic goals has been suggested as a means of optimizing the treatment of patients with candidaemia. However, data regarding species-specific dosing targets are inconclusive. We retrospectively analysed a cohort of 75 adult patients with Candida bloodstream infection (BSI) who received initial treatment with fluconazole for ≥48 h (36 Candida albicans and 39 non-albicans Candida (NAC)). Fluconazole dose, the dose/MIC ratio and the 24-h area under the concentration-time curve (AUC24)/MIC ratio were determined for each patient, and classification and regression tree analysis was used to determine breakpoints for significant interactions with 30-day survival. Both fluconazole exposure parameters and patient-related and disease-related variables were assessed in univariable and multivariable survival models. The crude 30-day mortality rate was 32% (44% and 21% for C. albicans and NAC, respectively). An average fluconazole dose of >200 mg/day, a dose/MIC ratio of >400 and an AUC24/MIC ratio of >400 were associated with a higher 30-day survival rate and better microbiological response in patients with C. albicans BSI but not in those with NAC BSI. Baseline chronic kidney disease was a risk factor for fluconazole underdosing and mortality. Severity of sepsis (Sequential Organ Failure Assessment score) was the only significant predictor of death in patients with NAC BSI. We conclude that, although pharmacodynamic target-directed fluconazole dosing may help to optimize outcomes for patients with C. albicans BSI, additional studies are needed to define the role of fluconazole in the treatment of NAC BSI.

  18. Differential association of fluconazole dose and dose/MIC ratio with mortality in patients with Candida albicans and non-albicans bloodstream infection.

    Science.gov (United States)

    Brosh-Nissimov, T; Ben-Ami, R

    2015-11-01

    Targeting fluconazole therapy to achieve predefined pharmacodynamic goals has been suggested as a means of optimizing the treatment of patients with candidaemia. However, data regarding species-specific dosing targets are inconclusive. We retrospectively analysed a cohort of 75 adult patients with Candida bloodstream infection (BSI) who received initial treatment with fluconazole for ≥48 h (36 Candida albicans and 39 non-albicans Candida (NAC)). Fluconazole dose, the dose/MIC ratio and the 24-h area under the concentration-time curve (AUC24)/MIC ratio were determined for each patient, and classification and regression tree analysis was used to determine breakpoints for significant interactions with 30-day survival. Both fluconazole exposure parameters and patient-related and disease-related variables were assessed in univariable and multivariable survival models. The crude 30-day mortality rate was 32% (44% and 21% for C. albicans and NAC, respectively). An average fluconazole dose of >200 mg/day, a dose/MIC ratio of >400 and an AUC24/MIC ratio of >400 were associated with a higher 30-day survival rate and better microbiological response in patients with C. albicans BSI but not in those with NAC BSI. Baseline chronic kidney disease was a risk factor for fluconazole underdosing and mortality. Severity of sepsis (Sequential Organ Failure Assessment score) was the only significant predictor of death in patients with NAC BSI. We conclude that, although pharmacodynamic target-directed fluconazole dosing may help to optimize outcomes for patients with C. albicans BSI, additional studies are needed to define the role of fluconazole in the treatment of NAC BSI. PMID:26183300

  19. Risk factors for pulmonary fungous infection caused by candida albicans versus non-albicans candida species%肺部白色念珠菌与非白色念珠菌感染危险因素的比较

    Institute of Scientific and Technical Information of China (English)

    黄睿; 辛建保

    2009-01-01

    目的 探讨肺部白色念珠菌与非白色念珠菌感染危险因素的差异.方法 对近5年我院176例侵袭性肺部真菌感染病例进行回顾性分析.结果 176例患者感染白色念珠菌120株(60.3%),非白色念珠菌79株(39.7%).除神经系统疾病分布倾向于非白色念珠菌组外,其他各系统疾病两组间分布比较无明显差异.年龄≥65岁患者趋向于感染白色念珠菌,年龄<65岁,入住ICU,接受各种医源性操作(气管插管/切开,机械通气,留置导尿管)的患者则趋向于感染非白色念珠菌.年龄≥65岁为白色念珠菌感染的独立危险因素,非白色念珠菌感染的危险因素为留置导尿管.结论 肺部白色念珠菌与非白色念珠菌感染危险因素的不同,有助于预防性抗真菌治疗药物的选择.%Objective This study we sought to identify differences in risk factors of invasive pulmonary fungous infection caused by Candida albicans and non-albicans candida species.Methods A retrospective chart review was conduct which including 176 patients with invasive pulmonary fungous infection during 2003-2005 in Wuhan Union Hospital.Results There were 176 patients to be infected with 120 strains of Candida albicans (60.3%) and 79 strains of non-albicans candida(39.7%).Except the nervous system disease,there was no significant different distribution of other underlaying diseases between the two groups.Patients whose age≥65 years were more likely to be infected with Candida albicans,while age<65years,in the intensive unit care and accept iatrogenic operations(tracheal intubation/incision, anical ventilation,urethral catheter in) were more likely to have non-albicans candida species infection.Multiple regression analysis showed the significant risk factor for Candida albicans was age≥65 years,and urethral catheter in was the significant risk factor for non-albicans candida species.Conclution The different in the risk factors between Candida albicans and non-albicans

  20. 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.

  1. Development of DNA probes for Candida albicans

    International Nuclear Information System (INIS)

    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 32P- 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. The adaptor CARD9 is required for adaptive but not innate immunity to oral mucosal Candida albicans infections.

    Science.gov (United States)

    Bishu, Shrinivas; Hernández-Santos, Nydiaris; Simpson-Abelson, Michelle R; Huppler, Anna R; Conti, Heather R; Ghilardi, Nico; Mamo, Anna J; Gaffen, Sarah L

    2014-03-01

    Oropharyngeal candidiasis (OPC [thrush]) is an opportunistic infection caused by the commensal fungus Candida albicans. OPC is common in individuals with HIV/AIDS, infants, patients on chemotherapy, and individuals with congenital immune defects. Immunity to OPC is strongly dependent on the interleukin-23 (IL-23)/IL-17R axis, as mice and humans with defects in IL-17R signaling (IL17F, ACT1, IL-17RA) or in genes that direct Th17 differentiation (STAT3, STAT1, CARD9) are prone to mucocutaneous candidiasis. Conventional Th17 cells are induced in response to C. albicans infection via signals from C-type lectin receptors, which signal through the adaptor CARD9, leading to production of Th17-inducing cytokines such as IL-6, IL-1β, and IL-23. Recent data indicate that IL-17 can also be made by numerous innate cell subsets. These innate "type 17" cells resemble conventional Th17 cells, but they can be activated without need for prior antigen exposure. Because C. albicans is not a commensal organism in rodents and mice are thus naive to this fungus, we had the opportunity to assess the role of CARD9 in innate versus adaptive responses using an OPC infection model. As expected, CARD9(-/-) mice failed to mount an adaptive Th17 response following oral Candida infection. Surprisingly, however, CARD9(-/-) mice had preserved innate IL-17-dependent responses to Candida and were almost fully resistant to OPC. Thus, CARD9 is important primarily for adaptive immunity to C. albicans, whereas alternate recognition systems appear to be needed for effective innate responses. PMID:24379290

  3. Candida albicans osteomyelitis of the cervical spine

    Energy Technology Data Exchange (ETDEWEB)

    Cha, Jang-Gyu; Hong, Hyun-Sook [Soonchunhyang University Bucheon Hospital, Department of Radiology, Bucheon-Si, Gyeonggi-Do (Korea); Koh, Yoon-Woo [Soonchunhyang University Bucheon Hospital, Department of Otolaryngology - Head and Neck Surgery, Bucheon-Si, Gyeonggi-Do (Korea); Kim, Hee-Kyung [Soonchunhyang University Bucheon Hospital, Department of Pathology, Bucheon-Si, Gyeonggi-Do (Korea); Park, Jung-Mi [Soonchunhyang University Bucheon Hospital, Department of Nuclear Medicine, Bucheon-Si, Gyeonggi-Do (Korea)

    2008-04-15

    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.)

  4. Candida albicans osteomyelitis of the cervical spine

    International Nuclear Information System (INIS)

    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.)

  5. Echinocandin to fluconazole step-down therapy in critically ill patients with invasive, susceptible Candida albicans infections.

    Science.gov (United States)

    van der Geest, Patrick J; Rijnders, Bart J A; Vonk, Alieke G; Groeneveld, A B Johan

    2016-03-01

    Invasive Candida spp. infections are increasingly diagnosed in critically ill patients. For initial treatment, an echinocandin is recommended with a possible step-down to fluconazole when the patients' condition is improving and the isolate appears susceptible, but there are no data to support such policy. We studied the safety and efficacy of step-down therapy in critically ill patients with culture proven deep seated or bloodstream infections by C. albicans susceptible to fluconazole. All patients admitted into the intensive care unit from January 2010 to December 2014, who had a culture proven invasive C. albicans infection and received initial treatment with an echinocandin for at least 4 days were included. Data on patient characteristics, treatment and vital outcomes were assessed. Of the 56 patients, 32 received step-down fluconazole therapy, at median day 5, whereas the echinocandin was continued in the other 24. No differences where seen in baseline characteristics or risk factors for invasive C. albicans infection between the two groups. Response rates were similar and no difference where seen in 28-day or 90-day mortality between the groups. Step-down therapy to fluconazole may be safe and effective in critically ill patients with invasive infections by C. albicans, susceptible to fluconazole, who have clinically improved as early as 4 days after start of treatment with an echinocandin.

  6. Novel nanoscale bacteriophage-based single-domain antibodies for the therapy of systemic infection caused by Candida albicans

    Science.gov (United States)

    Dong, Shuai; Shi, Hongxi; Cao, Donghui; Wang, Yicun; Zhang, Xintong; Li, Yan; Gao, Xiang; Wang, Li

    2016-01-01

    Candida albicans (C. albicans) is an important human commensal and opportunistic fungal pathogen. Secreted aspartyl proteinases (Saps) are a major virulence trait of C. albicans, and among these proteases Sap2 has the highest expression levels. It is possible that antibodies against Sap2 could provide an antifungal effect. In this study, two phages displaying anti-rSap2 single chain variable fragments (scFvs) were screened from human single fold scFv libraries, and their potential therapeutic roles were evaluated using a murine model infected by C. albicans. The in vivo efficacies were assessed by mortality rates, fungal burden and histological examination. Overall survival rates were significantly increased while the colony counts and infectious foci were significantly decreased after treatment with the scFv-phages relative to the control groups. In order to investigate the immune response provoked by scFv-phages, three kinds of cytokines (Th1, Th2 and Th17 types) were measured and a clear immune response was observed. These findings suggest that anti-rSap2 scFv-phages have potential in the therapy of systemic infection caused by C. albicans. PMID:27558409

  7. Novel nanoscale bacteriophage-based single-domain antibodies for the therapy of systemic infection caused by Candida albicans.

    Science.gov (United States)

    Dong, Shuai; Shi, Hongxi; Cao, Donghui; Wang, Yicun; Zhang, Xintong; Li, Yan; Gao, Xiang; Wang, Li

    2016-08-25

    Candida albicans (C. albicans) is an important human commensal and opportunistic fungal pathogen. Secreted aspartyl proteinases (Saps) are a major virulence trait of C. albicans, and among these proteases Sap2 has the highest expression levels. It is possible that antibodies against Sap2 could provide an antifungal effect. In this study, two phages displaying anti-rSap2 single chain variable fragments (scFvs) were screened from human single fold scFv libraries, and their potential therapeutic roles were evaluated using a murine model infected by C. albicans. The in vivo efficacies were assessed by mortality rates, fungal burden and histological examination. Overall survival rates were significantly increased while the colony counts and infectious foci were significantly decreased after treatment with the scFv-phages relative to the control groups. In order to investigate the immune response provoked by scFv-phages, three kinds of cytokines (Th1, Th2 and Th17 types) were measured and a clear immune response was observed. These findings suggest that anti-rSap2 scFv-phages have potential in the therapy of systemic infection caused by C. albicans.

  8. 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.

  9. The Adaptor CARD9 Is Required for Adaptive but Not Innate Immunity to Oral Mucosal Candida albicans Infections

    OpenAIRE

    Bishu, Shrinivas; Hernández-Santos, Nydiaris; Simpson-Abelson, Michelle R.; Huppler, Anna R; Conti, Heather R.; Ghilardi, Nico; Mamo, Anna J.; Sarah L Gaffen

    2014-01-01

    Oropharyngeal candidiasis (OPC [thrush]) is an opportunistic infection caused by the commensal fungus Candida albicans. OPC is common in individuals with HIV/AIDS, infants, patients on chemotherapy, and individuals with congenital immune defects. Immunity to OPC is strongly dependent on the interleukin-23 (IL-23)/IL-17R axis, as mice and humans with defects in IL-17R signaling (IL17F, ACT1, IL-17RA) or in genes that direct Th17 differentiation (STAT3, STAT1, CARD9) are prone to mucocutaneous ...

  10. Separation and Identification of Candida Albicans for Canine Surgical Infection%犬外科感染中白色念珠菌的分离鉴定

    Institute of Scientific and Technical Information of China (English)

    常向彩; 刘凌颖; 马明

    2015-01-01

    犬外科感染多以革兰氏阴性菌、革兰氏阳性菌混合感染为主,但近年来混有念珠菌、霉菌等真菌感染的病例呈增多趋势。文章对18例外科感染宠物犬创口中可能存在的白色念珠菌进行了分离鉴定,结果表明,18株样本中分离到白色念珠菌5株,分离率达27•8%,说明白色念珠菌在犬外科感染中占有一定比例。%Canine surgical infections ,mainly caused by Gramənegative bacteria and Graməpositive bacteria ,are showing an in‐creasing trend that mixed with Candida ,mold and other fungal.In this study ,there are 18 pet dogs of surgical wound infection in Candida albicans were isolated and identified .The results showed that :5 strains of Candida albicans were separated from 18 sam‐ples ,Candida albicans isolation rate was 27 .8% ,thus it can be seen that Candida albicans infection account for certain of dogs sur‐gical infection ,for the future to provide an important reference for surgical diagnosis and appropriate treatment of infection .

  11. Separation and Identification of Candida Albicans for Canine Surgical Infection%犬外科感染中白色念珠菌的分离鉴定

    Institute of Scientific and Technical Information of China (English)

    常向彩; 刘凌颖; 马明

    2015-01-01

    Canine surgical infections ,mainly caused by Gramənegative bacteria and Graməpositive bacteria ,are showing an in‐creasing trend that mixed with Candida ,mold and other fungal.In this study ,there are 18 pet dogs of surgical wound infection in Candida albicans were isolated and identified .The results showed that :5 strains of Candida albicans were separated from 18 sam‐ples ,Candida albicans isolation rate was 27 .8% ,thus it can be seen that Candida albicans infection account for certain of dogs sur‐gical infection ,for the future to provide an important reference for surgical diagnosis and appropriate treatment of infection .%犬外科感染多以革兰氏阴性菌、革兰氏阳性菌混合感染为主,但近年来混有念珠菌、霉菌等真菌感染的病例呈增多趋势。文章对18例外科感染宠物犬创口中可能存在的白色念珠菌进行了分离鉴定,结果表明,18株样本中分离到白色念珠菌5株,分离率达27•8%,说明白色念珠菌在犬外科感染中占有一定比例。

  12. Tetracycline Effects on Candida Albicans Virulence Factors

    OpenAIRE

    Logan McCool; Hanh Mai; Michael Essmann; Bryan Larsen

    2008-01-01

    Object. To determine if tetracycline, previously reported to increase the probability of developing symptomatic vaginal yeast infections, has a direct effect on Candida albicans growth or induction of virulent phenotypes. Method. In vitro, clinical isolates of yeast were cultivated with sublethal concentrations of tetracycline and yeast cell counts, hyphal formation, drug efflux pump activity, biofilm production, and hemolysin production were determined by previously reported methods. Resul...

  13. 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

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

    OpenAIRE

    Issam Alshami; Alharbi, Ahmed E

    2014-01-01

    Objective: 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. Methods: 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 ...

  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. Case analysis of 255 patients with candida albicans infection%255份白假丝酵母菌感染患者的病历分析

    Institute of Scientific and Technical Information of China (English)

    胡伟; 刘如品; 徐金霞; 田泾; 田锋奇

    2014-01-01

    目的:分析255份白假丝酵母菌感染患者的病历,为临床治疗提供参考。方法对255份白假丝酵母菌感染患者的病历进行分析,讨论患者一般资料、标本来源及药敏实验结果。结果白假丝酵母菌来源依次为痰液、分泌物、尿液、粪便、血液及其他;抗菌药物对白假丝酵母菌的敏感性依次为两性霉素、制霉菌素、氟胞嘧啶、酮康唑、咪康唑、氟康唑、伊曲康唑。结论白假丝酵母菌感染以老年患者居多,其中痰液检出率较高,白假丝酵母菌对两性霉素的敏感性高,值得临床推广应用。%Objective To analyze the case history of 255 patients with candida albicans infections, in order to provide references for clinical treatment. Methods The case history of 255 cases with candida albicans infection was analyzed. General information, specimen source and susceptibility testing results were discussed. Results The sources of candida albicans were sputum, secretion, urine, feces, blood, etc. Sensibility of antibacterial agents to candida albicans were amphotericin, nystatin, flucytosine, ketoconazole, miconazole, fluconazole and itraconazole. Conclusion The majority of the patients with candida albicans are the elderly. The sputum detection rate is high and the sensibility of candida albicans to amphotericin is high. It is worth popularization and application in clinic.

  17. 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.

  18. Candida albicans commensalism in the gastrointestinal tract.

    Science.gov (United States)

    Neville, B Anne; d'Enfert, Christophe; Bougnoux, Marie-Elisabeth

    2015-11-01

    Candida albicans is a polymorphic yeast species that often forms part of the commensal gastrointestinal mycobiota of healthy humans. It is also an important opportunistic pathogen. A tripartite interaction involving C. albicans, the resident microbiota and host immunity maintains C. albicans in its commensal form. The influence of each of these factors on C. albicans carriage is considered herein, with particular focus on the mycobiota and the approaches used to study it, models of gastrointestinal colonization by C. albicans, the C. albicans genes and phenotypes that are necessary for commensalism and the host factors that influence C. albicans carriage.

  19. Integrin αXβ₂ is a leukocyte receptor for Candida albicans and is essential for protection against fungal infections.

    Science.gov (United States)

    Jawhara, Samir; Pluskota, Elzbieta; Verbovetskiy, Dmitriy; Skomorovska-Prokvolit, Olena; Plow, Edward F; Soloviev, Dmitry A

    2012-09-01

    The opportunistic fungus Candida albicans is one of the leading causes of infections in immunocompromised patients, and innate immunity provides a principal mechanism for protection from the pathogen. In the present work, the role of integrin α(X)β₂ in the pathogenesis of fungal infection was assessed. Both purified α(X)β₂ and α(X)β₂-expressing human epithelial kidney 293 cells recognized and bound to the fungal hyphae of SC5314 strain of C. albicans but not to the yeast form or to hyphae of a strain deficient in the fungal mannoprotein, Pra1. The binding of the integrin to the fungus was inhibited by β-glucans but not by mannans, implicating a lectin-like activity in recognition but distinct in specificity from that of α(M)β₂. Mice deficient in α(X)β₂ were more prone to systemic infection with the LD₅₀ fungal inoculum decreasing 3-fold in α(X)β₂-deficient mice compared with wild-type mice. After challenging i.v. with 1.5 × 10⁴ cell/g, 60% of control C57BL/6 mice died within 14 d compared with 100% mortality of α(X)β₂-deficient mice within 9 d. Organs taken from α(X)β₂-deficient mice 16 h postinfection revealed a 10-fold increase in fungal invasion into the brain and a 2-fold increase into the liver. These data indicate that α(X)β₂ is important for protection against systemic C. albicans infections and macrophage subsets in the liver, Kupffer cells, and in the brain, microglial cells use α(X)β₂ to control fungal invasion.

  20. Hyphal content determines the compression strength of Candida albicans biofilms

    NARCIS (Netherlands)

    Paramonova, Ekaterina; Krom, Bastiaan P.; van der Mei, Henny C.; Busscher, Henk J.; Sharma, Prashant K.

    2009-01-01

    Candida albicans is the most frequently isolated human fungal pathogen among species causing biofilm-related clinical infections. Mechanical properties of Candida biofilms have hitherto been given no attention, despite the fact that mechanical properties are important for selection of treatment or d

  1. Genetic Relationship between Human and Animal Isolates of Candida albicans

    OpenAIRE

    Edelmann, Anke; Krüger, Monika; SCHMID, JAN

    2005-01-01

    Analyzing Candida albicans isolates from different human and animal individuals by Ca3 fingerprinting, we obtained no evidence for host-specific genotypes and for the existence of species-specific lineages, even though a certain degree of separation between human and animal isolates was found. Therefore, animals could potentially serve as reservoirs for human Candida infection.

  2. Clinical and molecular characteristics of bloodstream infections caused by Candida albicans in children from 2003 to 2011.

    Science.gov (United States)

    Tsai, M-H; Wang, S-H; Hsu, J-F; Lin, L-C; Chu, S-M; Huang, H-R; Chiang, M-C; Fu, R-H; Lu, J-J; Huang, Y-C

    2015-11-01

    We investigated the clinical and molecular characteristics of Candida albicans bloodstream infection (BSI) in children from a tertiary-level medical centre in Taiwan over a 9-year period from January 2003 to December 2011. We performed multilocus sequence typing (MLST) to investigate the genetic relatedness of these C. albicans BSI isolates. A total of 79 episodes of C. albicans BSI in 76 paediatric patients were identified, including 41 (51.9%) from the paediatric intensive care unit, 24 (30.4%) from the neonatal intensive care unit and 14 (17.7%) from general wards. More than half (59.5%) of these patients had underlying chronic co-morbidities, and the majority (94.9%) had a catheter or some other artificial device. All the isolates were susceptible to the antifungal agents tested. Only 32.9% (26/79) received effective antifungal agents within 24 h of onset of candidaemia. Twenty-five (31.6%) patients had persistent candidaemia (>3 days after the start of antifungal treatment) and candidaemia-attributable mortality rate was 22.8% (18/79). The 72 isolates available for MLST yielded 53 unique diploid sequence types (DSTs). Forty-five DSTs were singletons and eight DSTs were shared by 27 (37.5%) isolates. Seventy-one (98.6%) isolates were clustered within previously known clades. Based on the definition of two or more strains with shared DST occurring within a period of 90 days, 10.1% of the infections were categorized as nosocomial clusters, most commonly identified in the intensive care units. Although cluster-associated candidaemia was not associated with a higher mortality rate, none of the clusters were identified by the hospital infection control team.

  3. ANALYSIS OF RISK FACTORS OF CANDIDA ALBICANS VERSUS NON-ALBICANS INFECTIONS%非白念珠菌和白念珠菌感染危险因素的对比研究

    Institute of Scientific and Technical Information of China (English)

    冯文莉; 王艳青; 奚志琴; 杨静; 张润梅; 冀英; 吴媛; 贾晓强

    2011-01-01

    [Objective] To identify differences in risk factors and outcomes in hospital patients with Candida albicans and non-albicans infections. [Methods] A prospective case-control study was conducted to compare risk factors of 834 cases of Candida albicans, 256 cases of non-albicans infections and 1 220 cases of non-IFI in hospital patients of the Second Hospital of Shanxi Medical University. The risk factors of Candida albicans and non-albicans infections were analyzed by method of SPSS13.0 model. [Results] Univariate analysis and multivariate logistic regression analysis showed that age, course of disease, length of hospitalization, leucocyte count reducing, neutrocyte count reducing, albumin reducing, basic disease, prophylactic antifungal drugs, antibiotics, glucocorticoids, immunosuppressante, invasive examination and treatment were the risk factors for Candida albicans and non-albicans infections. Suffering from diseases of the urinary system, using of glucocorticoidsmore easily lead to non-albicans infections, but using the immunodepressants was more vulnerable to infection caused by Candida albicans. [Conclusion] The epidemiology of Candida infections is complex and varies among the different patients in hospital. The risk factors ate different between Candida albicans and non-albicans infections. Non-albicans infection was important in hospital patients. To efficiently control the risk factors should be emphasized, including early diagnosis, treatment of basic diseases, appropriate examine, prudent drug use, and shortening hospitalization.%[目的]探讨住院患者非白念珠菌感染和白念珠菌感染的流行病学特点以及发生的相关危险因素.[方法]采用病例对照研究方法,对256例非白念珠菌感染者、834例白念珠菌感染者以及1220例无真菌感染者进行危险因素比较,应用SPSS 13.0统计软件进行统计学分析.[结果]年龄、病程、住院时闻、白细胞及中性粒细胞计数减少、白蛋白降低

  4. 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.

  5. 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.

  6. Thymol has antifungal activity against Candida albicans during infection and maintains the innate immune response required for function of the p38 MAPK signaling pathway in Caenorhabditis elegans.

    Science.gov (United States)

    Shu, Chengjie; Sun, Lingmei; Zhang, Weiming

    2016-08-01

    The Caenorhabditis elegans model can be used to study Candida albicans virulence and host immunity, as well as to identify plant-derived natural products to use against C. albicans. Thymol is a hydrophobic phenol compound from the aromatic plant thyme. In this study, the in vitro data demonstrated concentration-dependent thymol inhibition of both C. albicans growth and biofilm formation during different developmental phases. With the aid of the C. elegans system, we performed in vivo assays, and our results further showed the ability of thymol to increase C. elegans life span during infection, inhibit C. albicans colony formation in the C. elegans intestine, and increase the expression levels of host antimicrobial genes. Moreover, among the genes that encode the p38 MAPK signaling pathway, mutation of the pmk-1 or sek-1 gene decreased the beneficial effects of thymol's antifungal activity against C. albicans and thymol's maintenance of the innate immune response in nematodes. Western blot data showed the level of phosphorylation of pmk-1 was dramatically decreased against C. albicans. In nematodes, treatment with thymol recovered the dysregulation of pmk-1 and sek-1 gene expressions, the phosphorylation level of PMK-1 caused by C. albicans infection. Therefore, thymol may act, at least in part, through the function of the p38 MAPK signaling pathway to protect against C. albicans infection and maintain the host innate immune response to C. albicans. Our results indicate that the p38 MAPK signaling pathway plays a crucial role in regulating the beneficial effects observed after nematodes infected with C. albicans were treated with thymol. PMID:26783030

  7. 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.

  8. Functional genomics identifies type I interferon pathway as central for host defense against Candida albicans

    NARCIS (Netherlands)

    Smeekens, Sanne P.; Ng, Aylwin; Kumar, Vinod; Johnson, Melissa D.; Plantinga, Theo S.; van Diemen, Cleo; Arts, Peer; Verwiel, Eugene T. P.; Gresnigt, Mark S.; Fransen, Karin; van Sommeren, Suzanne; Oosting, Marije; Cheng, Shih-Chin; Joosten, Leo A. B.; Hoischen, Alexander; Kullberg, Bart-Jan; Scott, William K.; Perfect, John R.; van der Meer, Jos W. M.; Wijmenga, Cisca; Netea, Mihai G.; Xavier, Ramnik J.

    2013-01-01

    Candida albicans is the most common human fungal pathogen causing mucosal and systemic infections. However, human antifungal immunity remains poorly defined. Here by integrating transcriptional analysis and functional genomics, we identified Candida-specific host defence mechanisms in humans. Candid

  9. INCIDENCE OF NON-CANDIDA ALBICANS IN PATIENTS WITH URINARY TRACT INFECTION WITH SPECIAL REFERENCE TO SPECIATIO N AND ANTIFUNGAL SUSCEPTIBILITY

    Directory of Open Access Journals (Sweden)

    Ragini Ananth

    2012-10-01

    Full Text Available ABSTRACT: BACKGROUND AND OBJECTIVES: Fungal urinary tract infections have become frequent, as a result of increased use of broad spec trum antibiotics, corticosteroids, immunosuppressive drugs and bladder catheters in acut e care settings. The associated risk factors which are seen in cases of candiduria are: antibiotic therapy, female gender, urinary catheterization, surgical procedure and extended hos pitalization. Candiduria has become a potential source of morbidity and mortality if untre ated. We undertook a prospective study to note the incidence of non-Candida albicans in patien ts with urinary tract infection with special reference to speciation, antifungal susceptibility an d the associated risk factors. METHODS: Candida species isolated from urine samples of patient s with urinary tract infection were subjected to speciation using standard yeast identif ication protocol and CHROM agar. Antifungal Susceptibility testing was done by the disc diffusio n method to amphotericin B and fluconazole. Clinical details and risk factors of the patients we re noted down. RESULTS: Among the 60 culture positive cases, six Candida species which wer e isolated are : C.tropicalis (66.66%, C.albicans (13.33%, C.parapsilosis (8.33%, C.glabr ata (6.66%, C.kefyr (3.33% and C.guilliermondii (1.66% The susceptibility pattern s howed, that of the 60 isolates, 40% were resistant to fluconazole. No resistance was seen to amphotericin B. CONCLUSION: Isolation of non-Candida albicans species was more than Candida a lbicans. Candida tropicalis was the predominant isolate. The following risk factors were noted: 43.33 % of the patients had diabetes mellitus, 30%had history of prolonged antib iotics (cephalosporin and aminoglycosides, 16.66% had underlying renal pathol ogy, 3.33% had post –renal transplant status, 1.66% were on steroids, 1.66%had pregnancy a nd 3.33% had no identifiable risk factors.20% patients had an indwelling catheter in them. The antifungal

  10. Characterization of extracellular nucleotide metabolism in Candida albicans.

    Science.gov (United States)

    Rodrigues, Lisa; Russo-Abrahão, Thais; Cunha, Rodrigo A; Gonçalves, Teresa; Meyer-Fernandes, José Roberto

    2016-01-01

    Candida albicans is the most frequent agent of human disseminated fungal infection. Ectophosphatase and ectonucleotidase activities are known to influence the infectious potential of several microbes, including other non-albicans species of Candida. With the present work we aim to characterize these ecto-enzymatic activities in C. albicans. We found that C. albicans does not have a classical ecto-5'-nucleotidase enzyme and 5'AMP is cleaved by a phosphatase instead of exclusively by a nucleotidase that also can use 3'AMP as a substrate. Moreover, these enzymatic activities are not dependent on secreted soluble enzymes and change when the yeast cells are under infection conditions, including low pH, and higher temperature and CO2 content.

  11. Expression of surface hydrophobic proteins by Candida albicans in vivo.

    OpenAIRE

    Glee, P M; Sundstrom, P; Hazen, K C

    1995-01-01

    Candida albicans modulates cell surface hydrophobicity during growth and morphogenesis in vitro. To determine if surface hydrophobicity is expressed during pathogenesis, we generated a polyclonal antiserum against yeast hydrophobic proteins. The antiserum was then used for indirect immunofluorescence analysis of tissues from mice colonized and chronically infected with C. albicans. Results demonstrated that yeast hydrophobic proteins are exposed on fungal cells present in host tissues. The po...

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Interactions of Candida albicans with host epithelial surfaces

    Directory of Open Access Journals (Sweden)

    David W. Williams

    2013-10-01

    Full Text Available Candida albicans is an opportunistic, fungal pathogen of humans that frequently causes superficial infections of oral and vaginal mucosal surfaces of debilitated and susceptible individuals. The organism is however, commonly encountered as a commensal in healthy individuals where it is a component of the normal microflora. The key determinant in the type of relationship that Candida has with its host is how it interacts with the epithelial surface it colonises. A delicate balance clearly exists between the potentially damaging effects of Candida virulence factors and the nature of the immune response elicited by the host. Frequently, it is changes in host factors that lead to Candida seemingly changing from a commensal to pathogenic existence. However, given the often reported heterogeneity in morphological and biochemical factors that exist between Candida species and indeed strains of C. albicans, it may also be the fact that colonising strains differ in the way they exploit resources to allow persistence at mucosal surfaces and as a consequence this too may affect the way Candida interacts with epithelial cells. The aim of this review is to provide an overview of some of the possible interactions that may occur between C. albicans and host epithelial surfaces that may in turn dictate whether Candida removal, its commensal persistence or infection follows.

  14. Candida albicans infection leads to barrier breakdown and a MAPK/NF-κB mediated stress response in the intestinal epithelial cell line C2BBe1.

    Science.gov (United States)

    Böhringer, Michael; Pohlers, Susann; Schulze, Sylvie; Albrecht-Eckardt, Daniela; Piegsa, Judith; Weber, Michael; Martin, Ronny; Hünniger, Kerstin; Linde, Jörg; Guthke, Reinhard; Kurzai, Oliver

    2016-07-01

    Intestinal epithelial cells (IEC) form a tight barrier to the gut lumen. Paracellular permeability of the intestinal barrier is regulated by tight junction proteins and can be modulated by microorganisms and other stimuli. The polymorphic fungus Candida albicans, a frequent commensal of the human mucosa, has the capacity of traversing this barrier and establishing systemic disease within the host. Infection of polarized C2BBe1 IEC with wild-type C. albicans led to a transient increase of transepithelial electric resistance (TEER) before subsequent barrier disruption, accompanied by a strong decline of junctional protein levels and substantial, but considerably delayed cytotoxicity. Time-resolved microarray-based transcriptome analysis of C. albicans challenged IEC revealed a prominent role of NF-κB and MAPK signalling pathways in the response to infection. Hence, we inferred a gene regulatory network based on differentially expressed NF-κB and MAPK pathway components and their predicted transcriptional targets. The network model predicted activation of GDF15 by NF-κB was experimentally validated. Furthermore, inhibition of NF-κB activation in C. albicans infected C2BBe1 cells led to enhanced cytotoxicity in the epithelial cells. Taken together our study identifies NF-κB activation as an important protective signalling pathway in the response of epithelial cells to C. albicans. PMID:26752615

  15. Comparison of risk factors for non-albicans candida and candida albicans infections in the intensive care unit%重症监护病房非白色念珠菌和白色念珠菌感染危险因素的比较

    Institute of Scientific and Technical Information of China (English)

    黄磊; 赵令玺; 张卫星; 罗华; 陈映群; 张声

    2010-01-01

    Objective To determine the differences of risk factors for non-albicans candida and candida albicans infections among patients in the intensive care unit (ICU). Methods One hundred and three patients with ICU-acquired candida infections were retrospectively analyzed from February 2003 to April 2009. These patients were divided into non-albicans candida species group and candida albicans group.Multiple risk factors were analyzed between two groups. Results Of these patients, 46 patients (44.7%)had infections of non-albicans candida species and 57 patients (55.3%) had candida albicans infection.Among non-albicans candida species, candida glabrata, candida parapsilosis, candida tropicalis, candida krusei and others candida accounted for 19 patients (18.4%), 13 patients (12.6%), 10 patients (9.7%), 2 patients (1.9%) and 2 patients ( 1.9% ), respectively. Multivariate Logistic regression models revealed that central venous catheter (CVC) insertion time > 2 d (OR = 32.477,95% CI:4.905-215.035,P=0.000),total parenteral nutrition (OR =3.119,95% CI:1.214-8.015,P =0.018) and fluconazole prophylaxis therapy (OR = 5.084,95%CI: 1.319-19.596,P = 0.018) were highly correlated with non-albicans candida species infections. Conclusion CVC insertion time > 2 d, total parenteral nutrition and fluconazole prophylaxis therapy are independent risk factors of non-albicans candida species infections and can be used in empirical antifungal therapy.%目的 研究重症监护病房(ICU)患者非白色念珠菌和白色念珠菌感染危险因素的差异.方法 回顾性分析2003年2月至2009年4月ICU获得性念珠菌感染患者103例,其中非白色念珠菌感染46例,白色念珠菌感染57例,对其多个危险因素进行统计学分析.结果 非白色念珠菌中,光滑念珠菌19例(18.4%),近平滑念珠菌13例(12.6%),热带念珠菌10例(9.7%),克柔念珠菌2例(1.9%),其他念珠菌2例(1.9%).经Logistic多因素回归分析发现,中心静脉导管(CVC)留置>2 d(OR=32

  16. Performance comparison of phenotypic and molecular methods for detection and differentiation of Candida albicans and Candida dubliniensis

    OpenAIRE

    Ahmad Suhail; Khan Ziauddin; Asadzadeh Mohammad; Theyyathel Ajmal; Chandy Rachel

    2012-01-01

    Abstract Background Candida albicans is the most pathogenic Candida species but shares many phenotypic features with Candida dubliniensis and may, therefore, be misidentified in clinical microbiology laboratories. Candidemia cases due to C. dubliniensis are increasingly being reported in recent years. Accurate identification is warranted since mortality rates are highest for C. albicans infections, however, C. dubliniensis has the propensity to develop resistance against azoles more easily. W...

  17. Interactions Between Candida albicans and Host Interações entre Candida albicans e Hospedeiro

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    Tatiane De Rossi

    2011-06-01

    Full Text Available Candida albicans can cause grave infections in patients who are immunocompromised by diseases, by surgery, or by immunesupresive therapy. The high levels of morbidity and mortality resulting from those infections in hospitalized patients show that C. albicans became a prominent human pathogen. Although the host immune system is the major factor balancing the transition from commensalisms to pathogenicity, several virulence attributes expressed by C. albicans, such as adhesion factors, phenotypic switching, dimorphic behavior, and secretion of hydrolytic enzymes, might contribute to the persistence of colonization as well as the development of symptomatic episodes. Host defense against candidiasis relies mainly on the ingestion and elimination of C. albicans by phagocytic cells, which present receptors Toll-like 4, dectin–1 associated to receptors Toll-like2 and mannose receptors. The cytokine IL-10 (IL-10 produced by phagocytes has a crucial role on susceptibility of host fungal infection, whereas IL-10 produced by regulatory T cells is mainly responsible by commensalisms. In contrast, productions of tumour necrosis factor - α (TNF-α, interleukin–1 β (lL-1 β, (IL-6 and (Il-12 provided protective cell–mediated immunity. The interferon-γ produced by natural killer and TH1 cells stimulates migration of phagocytes and major efficacy on destruction of fungi. In epithelial cells from mucosas the NOD-like receptors and defensins-β cytoplasmatic prevent the translocation of C. albicans from microbiota to tissues, which are modulated by IL-1 β, Il-17 and Il-22 cytokines. to pathogenicity, several virulence attributes expressed by C. albicans, such as adhesion factors, phenotypic switching, dimorphic behavior, and secretion of hydrolytic enzymes, might contribute to the persistence of colonization as well as the development of symptomatic episodes. Host defense against candidiasis relies mainly on the ingestion and elimination of C. albicans

  18. 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.

  19. Sensitization of Candida albicans to terbinafine by berberine and berberrubine

    Science.gov (United States)

    LAM, PIKLING; KOK, STANTON HON LUNG; LEE, KENNETH KA HO; LAM, KIM HUNG; HAU, DESMOND KWOK PO; WONG, WAI YEUNG; BIAN, ZHAOXIANG; GAMBARI, ROBERTO; CHUI, CHUNG HIN

    2016-01-01

    Candida albicans (C. albicans) is an opportunistic fungal pathogen, particularly observed in immunocompromised patients. C. albicans accounts for 50–70% of cases of invasive candidiasis in the majority of clinical settings. Terbinafine, an allylamine antifungal drug, has been used to treat fungal infections previously. It has fungistatic activity against C. albicans. Traditional Chinese medicines can be used as complementary medicines to conventional drugs to treat a variety of ailments and diseases. Berberine is a quaternary alkaloid isolated from the traditional Chinese herb, Coptidis Rhizoma, while berberrubine is isolated from the medicinal plant Berberis vulgaris, but is also readily derived from berberine by pyrolysis. The present study demonstrates the possible complementary use of berberine and berberrubine with terbinafine against C. albicans. The experimental findings assume that the potential application of these alkaloids together with reduced dosage of the standard drug would enhance the resulting antifungal potency. PMID:27073630

  20. Neutrophil activation by Candida glabrata but not Candida albicans promotes fungal uptake by monocytes.

    Science.gov (United States)

    Duggan, Seána; Essig, Fabian; Hünniger, Kerstin; Mokhtari, Zeinab; Bauer, Laura; Lehnert, Teresa; Brandes, Susanne; Häder, Antje; Jacobsen, Ilse D; Martin, Ronny; Figge, Marc Thilo; Kurzai, Oliver

    2015-09-01

    Candida albicans and Candida glabrata account for the majority of candidiasis cases worldwide. Although both species are in the same genus, they differ in key virulence attributes. Within this work, live cell imaging was used to examine the dynamics of neutrophil activation after confrontation with either C. albicans or C. glabrata. Analyses revealed higher phagocytosis rates of C. albicans than C. glabrata that resulted in stronger PMN (polymorphonuclear cells) activation by C. albicans. Furthermore, we observed differences in the secretion of chemokines, indicating chemotactic differences in PMN signalling towards recruitment of further immune cells upon confrontation with Candida spp. Supernatants from co-incubations of neutrophils with C. glabrata primarily attracted monocytes and increased the phagocytosis of C. glabrata by monocytes. In contrast, PMN activation by C. albicans resulted in recruitment of more neutrophils. Two complex infection models confirmed distinct targeting of immune cell populations by the two Candida spp.: In a human whole blood infection model, C. glabrata was more effectively taken up by monocytes than C. albicans and histopathological analyses of murine model infections confirmed primarily monocytic infiltrates in C. glabrata kidney infection in contrast to PMN-dominated infiltrates in C. albicans infection. Taken together, our data demonstrate that the human opportunistic fungi C. albicans and C. glabrata are differentially recognized by neutrophils and one outcome of this differential recognition is the preferential uptake of C. glabrata by monocytes.

  1. 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

  2. Principles of a New Protocol for Prediction of Azole Resistance in Candida albicans Infections on the Basis of ERG11 Polymorphisms.

    Science.gov (United States)

    Caban, Monika; Strapagiel, Dominik; Dziadek, Jarosław; Korycka-Machała, Małgorzata; Grzelak, Agnieszka

    2016-08-01

    In recent years, Candida albicans infections treatment has become a growing problem because, among others, pathogenic strains are capable to develop resistance to the administered drugs. The elaboration of rapid and accurate method of resistance assessment is an important goal of many studies. They aim to avoid inappropriate dosage or drug choice, which may be life threatening in case of severe candidiasis. Here we propose a new protocol to predict C. albicans infections. The resistance prediction is based on high-resolution melt (HRM) analysis of ERG11 gene, especially, at the particularly unstable regions. Two statistically significant nucleotide polymorphisms were detected among twenty-seven strains isolated from saliva, one of which was silent mutation (Glu266Asp, Leu480Leu). We propose also HRM analysis as a convenient, simple and inexpensive method of preliminary selection of C. albicans DNA samples that vary in ERG11 nucleotide sequence within presumed region. Taken together, our study provides firm basis for the development of fast, simple and reliable methodology for diagnosis of C. albicans infections. PMID:27107760

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

    Science.gov (United States)

    Gil-Alonso, Sandra; Jauregizar, Nerea; Eraso, Elena; Quindós, Guillermo

    2015-01-01

    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.

  4. Gymnemic acids inhibit hyphal growth and virulence in Candida albicans.

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    Govindsamy Vediyappan

    Full Text Available Candida albicans is an opportunistic and polymorphic fungal pathogen that causes mucosal, disseminated and invasive infections in humans. Transition from the yeast form to the hyphal form is one of the key virulence factors in C. albicans contributing to macrophage evasion, tissue invasion and biofilm formation. Nontoxic small molecules that inhibit C. albicans yeast-to-hypha conversion and hyphal growth could represent a valuable source for understanding pathogenic fungal morphogenesis, identifying drug targets and serving as templates for the development of novel antifungal agents. Here, we have identified the triterpenoid saponin family of gymnemic acids (GAs as inhibitor of C. albicans morphogenesis. GAs were isolated and purified from Gymnema sylvestre leaves, the Ayurvedic traditional medicinal plant used to treat diabetes. Purified GAs had no effect on the growth and viability of C. albicans yeast cells but inhibited its yeast-to-hypha conversion under several hypha-inducing conditions, including the presence of serum. Moreover, GAs promoted the conversion of C. albicans hyphae into yeast cells under hypha inducing conditions. They also inhibited conidial germination and hyphal growth of Aspergillus sp. Finally, GAs inhibited the formation of invasive hyphae from C. albicans-infected Caenorhabditis elegans worms and rescued them from killing by C. albicans. Hence, GAs could be useful for various antifungal applications due to their traditional use in herbal medicine.

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

    Institute of Scientific and Technical Information of China (English)

    Issam Alshami; Ahmed E Alharbi

    2014-01-01

    Objective: 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.Methods: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. Results: 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. Conclusions: 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.

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

    OpenAIRE

    Sunitha Jagalur Doddanna; Shilpa Patel; Madhusudan Astekar Sundarrao; Ravindra Setru Veerabhadrappa

    2013-01-01

    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 additio...

  7. Multi-Step Pathogenesis and Induction of Local Immune Response by Systemic Candida Albicans Infection in an Intravenous Challenge Mouse Model

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    Voon-Kin Chin

    2014-08-01

    Full Text Available Different murine species differ in their susceptibility to systemic infection with Candida albicans, giving rise to varied host immune responses, and this is compounded by variations in virulence of the different yeast strains used. Hence, this study was aimed at elucidating the pathogenesis of a clinical C. albicans isolate (HVS6360 in a murine intravenous challenge model by examining the different parameters which included the counts of red blood cells and associated components as well as the organ-specific expression profiles of cytokines and chemokines. Kidneys and brains of infected mice have higher fungal recovery rates as compared to other organs and there were extensive yeast infiltration with moderate to severe inflammation seen in kidney and brain tissues. Red blood cells (RBCs and haemoglobin (Hb counts were reduced throughout the infection period. Pattern recognition receptors (PRRs, chemokines and cytokine transcription profiles were varied among the different organs (kidney, spleen and brain over 72 h post infections. Transcription of most of the PRRs, cytokines and chemokines were suppressed at 72 h post infection in spleen while continuous expression of PRRs, cytokines and chemokines genes were seen in brain and kidney. Reduction in red blood cells and haemoglobin counts might be associated with the action of extracellular haemolysin enzyme and haeme oxygenase of C. albicans in conjunction with iron scavenging for the fungal growth. Renal cells responsible for erythropoietin production may be injured by the infection and hence the combined effect of haemolysis plus lack of erythropoietin-induced RBC replenishment leads to aggravated reduction in RBC numbers. The varied local host immune profiles among target organs during systemic C. albicans infection could be of importance for future work in designing targeted immunotherapy through immunomodulatory approaches.

  8. Emergence of non-albicans candida species in neonatal candidemia

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    Deepak Juyal

    2013-01-01

    Full Text Available Background: Candida species are one of the most common causes of blood stream infections among neonates and account for 9-13% of such infections. Although Candida albicans remains the most common fungal isolate from neonatal candidemia, longitudinal studies have detected a shift towards non-albicans Candida (NAC species. Aim: To examine the prevalence and epidemiology of candidemia among infants admitted to our hospital. Materials and Methods: Blood samples were collected from 548 neonates and only those which yielded pure growth of Candida spp. were included in the study. The isolates were identified as per standard mycological techniques and antifungal susceptibility (AFS was done by disc diffusion method. Results: Of the total 132 neonates included in the study, NAC species were responsible for 80.30% cases with C. parapsilosis (25.0% and C. tropicalis (21.97% as the most predominant species; whereas 19.70% of cases were caused by C. albicans. AFS results revealed that 65.91, 73.49, and 96.21% isolates were sensitive to fluconazole (FLK, itraconazole (ITR, and amphotericin B (AMB, respectively. Conclusion: Candidemia in neonates is an ominous prognostic sign and is an important entity in our hospital. Strict infection control strategies, appropriate preventive and therapeutic measures such as prophylactic antifungal use and a restrictive policy of antibiotic use should be implemented.

  9. Detection of Candida albicans by mass spectrometric fingerprinting.

    Science.gov (United States)

    Zehm, Sarah; Schweinitz, Simone; Würzner, Reinhard; Colvin, Hans Peter; Rieder, Josef

    2012-03-01

    Candida albicans is one of the most frequent causes of fungal infections in humans. Significant correlation between candiduria and invasive candidiasis has previously been described. The existing diagnostic methods are often time-consuming, cost-intensive and lack in sensitivity and specificity. In this study, the profile of low-molecular weight volatile compounds in the headspace of C. albicans-urine suspensions of four different fungal cell concentrations compared to nutrient media and urine without C. albicans was determined using proton-transfer reaction mass spectrometry (PTR-MS). At fungal counts of ≥1.5 × 10(5) colony forming units (CFU)/ml signals at 45, 47 and 73 atomic mass units (amu) highly significantly increased. At fungal counts of albicans-urine suspensions of different fungal cell concentrations. PTR-MS represents a promising approach to rapid, highly sensitive and non-invasive clinical diagnostics allowing qualitative and quantitative analysis.

  10. Candida albicans keratitis in an immunocompromised patient

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    H Mohammed J Hassan

    2010-10-01

    Full Text Available H Mohammed J Hassan1, Theocharis Papanikolaou2, Georgios Mariatos1, Amany Hammad3, Hala Hassan41Ophthalmology Department, Barnsley Hospital NHS Foundation Trust, South Yorkshire, England, UK; 2Ophthalmology Department, Cambridge University Hospitals NHS Foundation Trust, England, UK; 3Ophthalmology Department, Rotherham Hospital NHS Foundation Trust, England, UK; 4Corneal and External Disease Service, Moorfields Eye Hospital NHS Foundation Trust, London, England, UKPurpose: When investigating a case of unexplained corneal ulceration, we need to think of fungal infection and any predisposing factors.Methods: A case study of a corneal ulceration in a patient who was HIV positive with a devastating visual outcome.Results: Therapeutic corneal graft was necessary due to corneal perforation. Immunocompromised state of patient was retrospectively diagnosed.Conclusions: Candida albicans keratitis is an opportunistic infection of a compromised cornea, and sometimes unknowingly compromised host, which can be initially misdiagnosed. Despite intensive antifungal therapy, occasionally patients require corneal grafting to improve vision, and before it is possible to establish an accurate diagnosis.Keywords: fungal keratitis, corneal perforation, keratoplasty, human immunodeficiency virus, HIV

  11. Interleukin 17-Mediated Host Defense against Candida albicans

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    Florian Sparber

    2015-08-01

    Full Text Available Candida albicans is part of the normal microbiota in most healthy individuals. However, it can cause opportunistic infections if host defenses are breached, with symptoms ranging from superficial lesions to severe systemic disease. The study of rare congenital defects in patients with chronic mucocutaneous candidiasis led to the identification of interleukin-17 (IL-17 as a key factor in host defense against mucosal fungal infection. Experimental infections in mice confirmed the critical role of IL-17 in mucocutaneous immunity against C. albicans. Research on mouse models has also contributed importantly to our current understanding of the regulation of IL-17 production by different cellular sources and its effector functions in distinct tissues. In this review, we highlight recent findings on IL-17-mediated immunity against C. albicans in mouse and man.

  12. Comparison of the hemolytic activity between C. albicans and non-albicans Candida species.

    Science.gov (United States)

    Rossoni, Rodnei Dennis; Barbosa, Júnia Oliveira; Vilela, Simone Furgeri Godinho; Jorge, Antonio Olavo Cardoso; Junqueira, Juliana Campos

    2013-01-01

    The ability to produce enzymes, such as hemolysins, is an important virulence factor for the genus Candida.The objective of this study was to compare the hemolytic activity between C. albicansand non-albicans Candida species. Fifty strains of Candida species, isolated from the oral cavity of patients infected with HIV were studied. The isolates included the following species: C. albicans, C. dubliniensis, C. glabrata, C. tropicalis, C. krusei, C. parapsilosis, C. dubliniensis, C. norvegensis, C. lusitaniae, and C. guilliermondii. Hemolysin production was evaluated on Sabouraud dextrose agar containing chloramphenicol, blood, and glucose. A loop-full of pure Candidaculture was spot-inoculated onto plates and incubated at 37 ºC for 24 h in a 5% CO2 atmosphere. Hemolytic activity was defined as the formation of a translucent halo around the colonies. All C. albicansstrains that were studied produced hemolysins. Among the non-albicans Candidaspecies, 86% exhibited hemolytic activity. Only C. guilliermondiiand some C. parapsilosis isolates were negative for this enzyme. In conclusion, most non-albicans Candidaspecies had a similar ability to produce hemolysins when compared to C. albicans.

  13. Elevated Cell Wall Chitin in Candida albicans Confers Echinocandin Resistance In Vivo

    OpenAIRE

    Lee, K K; MacCallum, D.M; Jacobsen, M.D.; Walker, L A; Odds, F C; Gow, N. A. R.; Munro, C.A.

    2012-01-01

    Candida albicans cells with increased cell wall chitin have reduced echinocandin susceptibility in vitro. The aim of this study was to investigate whether C. albicans cells with elevated chitin levels have reduced echinocandin susceptibility in vivo. BALB/c mice were infected with C. albicans cells with normal chitin levels and compared to mice infected with high-chitin cells. Caspofungin therapy was initiated at 24 h postinfection. Mice infected with chitin-normal cells were successfully tre...

  14. The persistence of multifocal colonisation by a single ABC genotype of Candida albicans may predict the transition from commensalism to infection

    OpenAIRE

    Guilherme Maranhão Chaves; Fernanda Pahim Santos; Arnaldo Lopes Colombo

    2012-01-01

    Candida albicans is a common member of the human microbiota and may cause invasive disease in susceptible populations. Several risk factors have been proposed for candidaemia acquisition. Previous Candida multifocal colonisation among hospitalised patients may be crucial for the successful establishment of candidaemia. Nevertheless, it is still not clear whether the persistence or replacement of a single clone of C. albicans in multiple anatomical sites of the organism may represent an additi...

  15. An essential role for the NLRP3 inflammasome in host defense against the human fungal pathogen, Candida albicans

    OpenAIRE

    Hise, Amy G.; Tomalka, Jeffrey; Ganesan, Sandhya; Patel, Krupen; Hall, Brian A.; Brown, Gordon D.; Fitzgerald, Katherine A.

    2009-01-01

    Candida albicans is an opportunistic fungal pathogen causing life-threatening mucosal and systemic infections in immunocompromised humans. Using a murine model of mucosal Candida infection we investigated the role of the proinflammatory cytokine IL-1β in host-defense to Candida albicans. We find that the synthesis, processing and release of IL-1β in response to Candida are tightly controlled and first require transcriptional induction, followed by a second signal leading to caspase-1 mediated...

  16. Enhanced efficacy of synergistic combinations of antimicrobial peptides with caspofungin versus Candida albicans in insect and murine models of systemic infection.

    Science.gov (United States)

    MacCallum, D M; Desbois, A P; Coote, P J

    2013-08-01

    The objective of this study was to determine whether combinations of antimicrobial peptides (AMPs) with caspofungin display enhanced antifungal activity versus Candida albicans in vitro and in vivo. Three conventional AMPs that satisfied criteria favouring their potential development as novel antifungals were selected for investigation. Colistin sulphate was also included as a cyclic peptide antibiotic used in the clinic. Minimum inhibitory concentrations (MICs) were determined for each antifungal agent and checkerboard assays were used to determine fractional inhibitory concentration index (FICI) values for dual combinations of AMPs or colistin with caspofungin. Viability assays were performed for the same combinations in order to investigate fungicidal interactions. Synergistic antifungal combinations were then tested for efficacy in vivo and compared to monotherapies in wax moth larva and murine models of systemic C. albicans infection. In combination with caspofungin, each of the AMPs [hMUC7-12, DsS3(1-16), hLF(1-11)] and colistin were synergistic and candidacidal in vitro. The treatment of infected wax moth larvae with combinations of caspofungin with hMUC7-12, DsS3(1-16) or colistin resulted in significant enhancements in survival compared to treatment with monotherapies. Notably, the treatment of C. albicans-infected mice with a combination of caspofungin and DsS3(1-16) resulted in the enhancement of survival compared to groups treated with just the individual agents. This study demonstrates that combination therapies containing caspofungin and AMPs or colistin merit further development as potential novel treatments for C. albicans infections. PMID:23572153

  17. Oxidative stress of photodynamic antimicrobial chemotherapy inhibits Candida albicans virulence

    Science.gov (United States)

    Kato, Ilka Tiemy; Prates, Renato Araujo; Tegos, George P.; Hamblin, Michael R.; Simões Ribeiro, Martha

    2011-03-01

    Photodynamic antimicrobial chemotherapy (PACT) is based on the principal that microorganisms will be inactivated using a light source combined to a photosensitizing agent in the presence of oxygen. Oxidative damage of cell components occurs by the action of reactive oxygen species leading to cell death for microbial species. It has been demonstrated that PACT is highly efficient in vitro against a wide range of pathogens, however, there is limited information for its in vivo potential. In addition, it has been demonstrated that sublethal photodynamic inactivation may alter the virulence determinants of microorganisms. In this study, we explored the effect of sublethal photodynamic inactivation to the virulence factors of Candida albicans. Methylene Blue (MB) was used as photosensitizer for sublethal photodynamic challenge on C. albicans associated with a diode laser irradiation (λ=660nm). The parameters of irradiation were selected in causing no reduction of viable cells. The potential effects of PACT on virulence determinants of C. albicans cells were investigated by analysis of germ tube formation and in vivo pathogenicity assays. Systemic infection was induced in mice by the injection of fungal suspension in the lateral caudal vein. C. albicans exposed to sublethal photodynamic inactivation formed significantly less germ tube than untreated cells. In addition, mice infected with C. albicans submitted to sublethal PACT survived for a longer period of time than mice infected with untreated cells. The oxidative damage promoted by sublethal photodynamic inactivation inhibited virulence determinants and reduced in vivo pathogenicity of C. albicans.

  18. Manipulation of host diet to reduce gastrointestinal colonization by the opportunistic pathogen Candida albicans

    Science.gov (United States)

    Candida albicans, the most common human fungal pathogen, can cause systemic infections with a mortality rate of ~40%. Infections arise from colonization of the gastrointestinal (GI) tract, where C. albicans is part of the normal microflora. Reducing colonization in at-risk patients using antifungal ...

  19. In vitro activity of eugenol against Candida albicans biofilms.

    Science.gov (United States)

    He, Miao; Du, Minquan; Fan, Mingwen; Bian, Zhuan

    2007-03-01

    Most manifestations of candidiasis are associated with biofilm formation occurring on the surfaces of host tissues and medical devices. Candida albicans is the most frequently isolated causative pathogen of candidiasis, and the biofilms display significantly increased levels of resistance to the conventional antifungal agents. Eugenol, the major phenolic component of clove essential oil, possesses potent antifungal activity. The aim of this study was to investigate the effects of eugenol on preformed biofilms, adherent cells, subsequent biofilm formation and cell morphogenesis of C. albicans. Eugenol displayed in vitro activity against C. albicans cells within biofilms, when MIC(50) for sessile cells was 500 mg/L. C. albicans adherent cell populations (after 0, 1, 2 and 4 h of adherence) were treated with various concentrations of eugenol (0, 20, 200 and 2,000 mg/L). The extent of subsequent biofilm formation were then assessed with the tetrazolium salt reduction assay. Effect of eugenol on morphogenesis of C. albicans cells was observed by scanning electron microscopy (SEM). The results indicated that the effect of eugenol on adherent cells and subsequent biofilm formation was dependent on the initial adherence time and the concentration of this compound, and that eugenol can inhibit filamentous growth of C. albicans cells. In addition, using human erythrocytes, eugenol showed low hemolytic activity. These results indicated that eugenol displayed potent activity against C. albicans biofilms in vitro with low cytotoxicity and therefore has potential therapeutic implication for biofilm-associated candidal infections. PMID:17356790

  20. White-opaque switching in Candida albicans

    OpenAIRE

    Lohse, Matthew B.; Johnson, Alexander D.

    2009-01-01

    The human commensal yeast Candida albicans undergoes an epigenetic switch between two distinct types of cells, referred to as white and opaque. These two cell types differ in many respects, including their cell and colony morphologies, their metabolic states, their mating behaviors, their preferred niches in the host, and their interactions with the host immune system. Each of the two cell types is heritable for many generations and switching between them appears stochastic; however, environm...

  1. The parasexual lifestyle of Candida albicans.

    Science.gov (United States)

    Bennett, Richard J

    2015-12-01

    Candida albicans is both a prevalent human commensal and the most commonly encountered human fungal pathogen. This lifestyle is dependent on the ability of the fungus to undergo rapid genetic and epigenetic changes, often in response to specific environmental cues. A parasexual cycle in C. albicans has been defined that includes several unique properties when compared to the related model yeast, Saccharomyces cerevisiae. Novel features include strict regulation of mating via a phenotypic switch, enhanced conjugation within a sexual biofilm, and a program of concerted chromosome loss in place of a conventional meiosis. It is expected that several of these adaptations co-evolved with the ability of C. albicans to colonize the mammalian host.

  2. Candida albicans adhesion to composite resin materials.

    Science.gov (United States)

    Bürgers, Ralf; Schneider-Brachert, Wulf; Rosentritt, Martin; Handel, Gerhard; Hahnel, Sebastian

    2009-09-01

    The adhesion of Candida albicans to dental restorative materials in the human oral cavity may promote the occurrence of oral candidosis. This study aimed to compare the susceptibility of 14 commonly used composite resin materials (two compomers, one ormocer, one novel silorane, and ten conventional hybrid composites) to adhere Candida albicans. Differences in the amount of adhering fungi should be related to surface roughness, hydrophobicity, and the type of matrix. Cylindrical specimens of each material were made according to the manufacturers' instructions. Surface roughness R (a) was assessed by perthometer measurements and the degree of hydrophobicity by computerized contact angle analysis. Specimens were incubated with a reference strain of C. albicans (DMSZ 1386), and adhering fungi were quantified by using a bioluminometric assay in combination with an automated plate reader. Statistical differences were analyzed by the Kruskal-Wallis test and Mann-Whitney U test. Spearman's rank correlation coefficients were calculated to assess correlations. Median R (a) of the tested composite resin materials ranged between 0.04 and 0.23 microm, median contact angles between 69.2 degrees and 86.9 degrees . The two compomers and the ormocer showed lower luminescence intensities indicating less adhesion of fungi than all tested conventional hybrid composites. No conclusive correlation was found between surface roughness, hydrophobicity, and the amount of adhering C. albicans.

  3. Multi-species biofilm of Candida albicans and non-Candida albicans Candida species on acrylic substrate

    Directory of Open Access Journals (Sweden)

    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.

  4. 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.

  5. Intestinal colonization with Candida albicans and mucosal immunity

    Institute of Scientific and Technical Information of China (English)

    Xiao-Dong Bai; Xian-Hua Liu; Qing-Ying Tong

    2004-01-01

    AIM: To observe the relationship between intestinal lumen colonization with Candida albicans and mucosal secretory IgA (sIgA).METHODS: A total of 82 specific-pathogen-free mice were divided randomly into control and colonization groups. After Candida albicans were inoculated into specific-pathogenfree mice, the number of Candida albicans adhering to cecum and mucosal membrane was counted. The lymphocyte proliferation in Peyer's patch and in lamina propria was shown by BrdU incorporation, while mucosal sIgA (surface membrane) isotype switch in Peyer's patch was investigated. IgA plasma cells in lamina propria were observed by immunohistochemical staining. Specific IgA antibodies to Candida albicans were measured with ELISA.RESULTS: From d 3 to d 14 after Candida albicans gavaging to mice, the number of Candida albicans colonizing in lumen and adhering to mucosal membrane was sharply reduced.Candida albicans translocation to mesenteric lymph nodes occurred at early time points following gavage administration and disappeared at later time points. Meanwhile, the content of specific IgA was increased obviously. Proliferation and differentiation of lymphocytes in lamina propria were also increased.CONCLUSION: Lymphocytes in lamina propria play an important role in intestinal mucosal immunity of specificpathogen-free mice when they are first inoculated with Candida albicans. The decreasing number of Candida albicans in intestine is related to the increased level of specific IgA antibodies in the intestinal mucus.

  6. Medical treatment of a pacemaker endocarditis due to Candida albicans and to Candida glabrata.

    Science.gov (United States)

    Roger, P M; Boissy, C; Gari-Toussaint, M; Foucher, R; Mondain, V; Vandenbos, F; le Fichoux, Y; Michiels, J F; Dellamonica, P

    2000-09-01

    We describe a case of pacemaker infection due to two fungal species: Candida albicans and C. glabrata. Transthoracic echocardiography showed a large vegetation on the intraventricular wires. Because of severe underlying diseases, surgery was believed to be contraindicated. The patient was treated using high dose of fluconazole, resulting in clinical improvement and negative blood cultures. However, 2 months later, the patient underwent a fatal stroke. At autopsy, a large vegetation was found only all along the wires. Postmortem culture of the infected material was positive for both C. albicans and C. glabrata. PMID:11023765

  7. Prostaglandins from Cytosolic Phospholipase A2α/Cyclooxygenase-1 Pathway and Mitogen-activated Protein Kinases Regulate Gene Expression in Candida albicans-infected Macrophages.

    Science.gov (United States)

    Yun, Bogeon; Lee, HeeJung; Jayaraja, Sabarirajan; Suram, Saritha; Murphy, Robert C; Leslie, Christina C

    2016-03-25

    In Candida albicans-infected resident peritoneal macrophages, activation of group IVA cytosolic phospholipase A2(cPLA2α) by calcium- and mitogen-activated protein kinases triggers the rapid production of prostaglandins I2 and E2 through cyclooxygenase (COX)-1 and regulates gene expression by increasing cAMP. InC. albicans-infected cPLA2α(-/-)or COX-1(-/-)macrophages, expression ofI l10,Nr4a2, and Ptgs2 was lower, and expression ofTnfα was higher, than in wild type macrophages. Expression was reconstituted with 8-bromo-cAMP, the PKA activator 6-benzoyl-cAMP, and agonists for prostaglandin receptors IP, EP2, and EP4 in infected but not uninfected cPLA2α(-/-)or COX-1(-/-)macrophages. InC. albicans-infected cPLA2α(+/+)macrophages, COX-2 expression was blocked by IP, EP2, and EP4 receptor antagonists, indicating a role for both prostaglandin I2 and E2 Activation of ERKs and p38, but not JNKs, by C. albicansacted synergistically with prostaglandins to induce expression of Il10,Nr4a2, and Ptgs2. Tnfα expression required activation of ERKs and p38 but was suppressed by cAMP. Results using cAMP analogues that activate PKA or Epacs suggested that cAMP regulates gene expression through PKA. However, phosphorylation of cAMP-response element-binding protein (CREB), the cAMP-regulated transcription factor involved inIl10,Nr4a2,Ptgs2, andTnfα expression, was not mediated by cAMP/PKA because it was similar inC. albicans-infected wild type and cPLA2α(-/-)or COX-1(-/-)macrophages. CREB phosphorylation was blocked by p38 inhibitors and induced by the p38 activator anisomycin but not by the PKA activator 6-benzoyl-cAMP. Therefore, MAPK activation inC. albicans-infected macrophages plays a dual role by promoting the cPLA2α/prostaglandin/cAMP/PKA pathway and CREB phosphorylation that coordinately regulate immediate early gene expression.

  8. Phenotypic consequences of LYS4 gene disruption in Candida albicans.

    Science.gov (United States)

    Gabriel, Iwona; Kur, Krzysztof; Laforce-Nesbitt, Sonia S; Pulickal, Anoop S; Bliss, Joseph M; Milewski, Sławomir

    2014-08-01

    A BLAST search of the Candida Genome Database with the Saccharomyces cerevisiae LYS4 sequence known to encode homoaconitase (HA) revealed ORFs 19.3846 and 19.11327. Both alleles of the LYS4 gene were sequentially disrupted in Candida albicans BWP17 cells using PCR-based methodology. The null lys4Δ mutant exhibited lysine auxotrophy in minimal medium but was able to grow in the presence of l-Lys and α-aminoadipate, an intermediate of the α-aminoadipate pathway, at millimolar concentrations. The presence of d-Lys and pipecolic acid did not trigger lys4Δ growth. The C. albicans lys4Δ mutant cells demonstrated diminished germination ability. However, their virulence in vivo in a murine model of disseminated neonatal candidiasis appeared identical to that of the wild-type strain. Moreover, there was no statistically significant difference in fungal burden of infected tissues between the strains.

  9. Evaluation of a Rapid Immunochromatographic Assay for Identification of Candida albicans and Candida dubliniensis

    OpenAIRE

    Marot-Leblond, Agnes; Grimaud, Linda; David, Sandrine; Sullivan, Derek J.; Coleman, David C.; Ponton, Jose; Robert, Raymond

    2004-01-01

    Candida dubliniensis was first established as a novel yeast species in 1995. It is particularly associated with recurrent episodes of oral candidosis in human immunodeficiency virus (HIV)-infected patients, but it has also been detected at other anatomical sites and at a low incidence level in non-HIV-infected patients. It shares so many phenotypic characteristics with C. albicans that it is easily misidentified as such. No rapid, simple, and commercial test that allows differentiation betwee...

  10. PREVALENCE OF BIOFILM PRODUCING MDR CANDIDA ALBICANS AND NON CANDIDA ALBICANS ISOLATE FROM MEDICAL DEVICES

    Directory of Open Access Journals (Sweden)

    P. Rajeswari

    2012-12-01

    Full Text Available Totally 56% of occurrence was observed from 6 types of sources. Among them highest prevalence was observed from urinary catheter (68% next in line is intravenous tubes (66.66%, venflon needles (65%, and blood bags (53.33% respectively. Four types of Candida species were identified by using selective media and biochemical tests. The Candida albicans was predominant isolates in all sources especially in urinary catheter. In this study, 60.2% of non Candida albicans were observed. All isolates were subjected to antifungal stability test, 6 antifungal agents were used. Among the 6 antifungal agents Itraconazole had highly resistance activity and Fluconazole had highly sensitive activity against the isolates. The antifungal resistance of isolates were highly observed in non Candida albicans such as Candida tropicalis (83.3% and followed by Candida glabrata (74.5%. All isolates were have the ability to produce biofilm, among them 37.4% of isolates were strong biofilm producer and 100% of protease producing isolates were observed in the last part of the study.

  11. Candida albicans mutant construction and characterization of selected virulence determinants.

    Science.gov (United States)

    Motaung, T E; Albertyn, J; Pohl, C H; Köhler, Gerwald

    2015-08-01

    Candida albicans is a diploid, polymorphic yeast, associated with humans, where it mostly causes no harm. However, under certain conditions it can cause infections ranging from superficial to life threatening. This ability to become pathogenic is often linked to the immune status of the host as well as the expression of certain virulence factors by the yeast. Due to the importance of C. albicans as a pathogen, determination of the molecular mechanisms that allow this yeast to cause disease is important. These studies rely on the ability of researchers to create deletion mutants of specific genes in order to study their function. This article provides a critical review of the important techniques used to create deletion mutants in C. albicans and highlights how these deletion mutants can be used to determine the role of genes in the expression of virulence factors in vitro.

  12. Coaggregation of Candida albicans, Actinomyces naeslundii and Streptococcus mutans is Candida albicans strain dependent.

    Science.gov (United States)

    Arzmi, Mohd Hafiz; Dashper, Stuart; Catmull, Deanne; Cirillo, Nicola; Reynolds, Eric C; McCullough, Michael

    2015-08-01

    Microbial interactions are necessarily associated with the development of polymicrobial oral biofilms. The objective of this study was to determine the coaggregation of eight strains of Candida albicans with Actinomyces naeslundii and Streptococcus mutans. In autoaggregation assays, C. albicans strains were grown in RPMI-1640 and artificial saliva medium (ASM) whereas bacteria were grown in heart infusion broth. C. albicans, A. naeslundii and S. mutans were suspended to give 10(6), 10(7) and 10(8) cells mL(-1) respectively, in coaggregation buffer followed by a 1 h incubation. The absorbance difference at 620 nm (ΔAbs) between 0 h and 1 h was recorded. To study coaggregation, the same protocol was used, except combinations of microorganisms were incubated together. The mean ΔAbs% of autoaggregation of the majority of RPMI-1640-grown C. albicans was higher than in ASM grown. Coaggregation of C. albicans with A. naeslundii and/or S. mutans was variable among C. albicans strains. Scanning electron microscopy images showed that A. naeslundii and S. mutans coaggregated with C. albicans in dual- and triculture. In conclusion, the coaggregation of C. albicans, A. naeslundii and S. mutans is C. albicans strain dependent. PMID:26054855

  13. Virulence and pathogenicity of Candida albicans is enhanced in biofilms containing oral bacteria.

    Science.gov (United States)

    Cavalcanti, Yuri Wanderley; Morse, Daniel James; da Silva, Wander José; Del-Bel-Cury, Altair Antoninha; Wei, Xiaoqing; Wilson, Melanie; Milward, Paul; Lewis, Michael; Bradshaw, David; Williams, David Wynne

    2015-01-01

    This study examined the influence of bacteria on the virulence and pathogenicity of candidal biofilms. Mature biofilms (Candida albicans-only, bacteria-only, C. albicans with bacteria) were generated on acrylic and either analysed directly, or used to infect a reconstituted human oral epithelium (RHOE). Analyses included Candida hyphae enumeration and assessment of Candida virulence gene expression. Lactate dehydrogenase (LDH) activity and Candida tissue invasion following biofilm infection of the RHOE were also measured. Candida hyphae were more prevalent (p biofilms also containing bacteria, with genes encoding secreted aspartyl-proteinases (SAP4/SAP6) and hyphal-wall protein (HWP1) up-regulated (p biofilm infections of RHOE. Multi-species infections exhibited higher hyphal proportions (p biofilms promoted Candida virulence, consideration should be given to the bacterial component when managing denture biofilm associated candidoses.

  14. Ocimum sanctum essential oil inhibits virulence attributes in Candida albicans.

    Science.gov (United States)

    Khan, Amber; Ahmad, Aijaz; Xess, Immaculata; Khan, Luqman A; Manzoor, Nikhat

    2014-03-15

    Candida albicans is an opportunistic human fungal pathogen which causes disease mainly in immunocompromised patients. Activity of hydrolytic enzymes is essential for virulence of C. albicans and so is the capacity of these cells to undergo transition from yeast to mycelial form of growth. Ocimum sanctum is cultivated worldwide for its essential oil which exhibits medicinal properties. This work evaluates the anti-virulence activity of O. sanctum essential oil (OSEO) on 22 strains of C. albicans (including a standard strain ATCC 90028) isolated from both HIV positive and HIV negative patients. Candida isolates were exposed to sub-MICs of OSEO. In vitro secretion of proteinases and phospholipases was evaluated by plate assay containing BSA and egg yolk respectively. Morphological transition from yeast to filamentous form was monitored microscopically in LSM. For genetic analysis, respective genes associated with morphological transition (HWP1), proteinase (SAP1) and phospholipase (PLB2) were also investigated by Real Time PCR (qRT-PCR). Results were analyzed using Student's t-test. OSEO inhibits morphological transition in C. albicans and had a significant inhibitory effect on extracellular secretion of proteinases and phospholipases. Expression profile of respective selected genes associated with C. albicans virulence by qRT-PCR showed a reduced expression of HWP1, SAP1 and PLB2 genes in cells treated with sub-inhibitory concentrations of OSEO. This work suggests that OSEO inhibits morphological transition in C. albicans and decreases the secretion of hydrolytic enzymes involved in the early stage of infection as well as down regulates the associated genes. Further studies will assess the clinical application of OSEO and its constituents in the treatment of fungal infections. PMID:24252340

  15. 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...

  16. New type of antibody-enzyme conjugate which specifically kills Candida albicans.

    OpenAIRE

    Okuda, K; Ishiwara, K; Noguchi, Y.; Takahashi, T.; Tadokoro, I

    1980-01-01

    A new type of antibody-enzyme conjugate was made, and its possible application to Candida infection was studied. Both lactoperoxidase and xanthine oxidase were conjugated to specific antibody against Candida albicans. In vitro microbiocidal activity of the new antibody-enzyme conjugate, when incubated together with xanthine and minute amount of halides, showed a remarkable level of candidacidal ability. When the new antibody-enzyme conjugate was given to Candida-infected mice, followed by inj...

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

    OpenAIRE

    Nouri, F; A. Raoofi; S. Dadfar

    2016-01-01

    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 dentu...

  18. Candida species biofilm and Candida albicans ALS3 polymorphisms in clinical isolates.

    Science.gov (United States)

    Bruder-Nascimento, Ariane; Camargo, Carlos Henrique; Mondelli, Alessandro Lia; Sugizaki, Maria Fátima; Sadatsune, Terue; Bagagli, Eduardo

    2014-01-01

    Over the last decades, there have been important changes in the epidemiology of Candida infections. In recent years, Candida species have emerged as important causes of invasive infections mainly among immunocompromised patients. This study analyzed Candida spp. isolates and compared the frequency and biofilm production of different species among the different sources of isolation: blood, urine, vulvovaginal secretions and peritoneal dialysis fluid. Biofilm production was quantified in 327 Candida isolates obtained from patients attended at a Brazilian tertiary public hospital (Botucatu, Sao Paulo). C. albicans ALS3 gene polymorphism was also evaluated by determining the number of repeated motifs in the central domain. Of the 198 total biofilm-positive isolates, 72 and 126 were considered as low and high biofilm producers, respectively. Biofilm production by C. albicans was significantly lower than that by non-albicans isolates and was most frequently observed in C. tropicalis. Biofilm production was more frequent among bloodstream isolates than other clinical sources, in urine, the isolates displayed a peculiar distribution by presenting two distinct peaks, one containing biofilm-negative isolates and the other containing isolates with intense biofilm production. The numbers of tandem-repeat copies per allele were not associated with biofilm production, suggesting the evolvement of other genetic determinants.

  19. Candida species biofilm and Candida albicans ALS3 polymorphisms in clinical isolates

    Directory of Open Access Journals (Sweden)

    Ariane Bruder-Nascimento

    2014-12-01

    Full Text Available Over the last decades, there have been important changes in the epidemiology of Candida infections. In recent years, Candida species have emerged as important causes of invasive infections mainly among immunocompromised patients. This study analyzed Candida spp. isolates and compared the frequency and biofilm production of different species among the different sources of isolation: blood, urine, vulvovaginal secretions and peritoneal dialysis fluid. Biofilm production was quantified in 327 Candida isolates obtained from patients attended at a Brazilian tertiary public hospital (Botucatu, Sao Paulo. C. albicans ALS3 gene polymorphism was also evaluated by determining the number of repeated motifs in the central domain. Of the 198 total biofilm-positive isolates, 72 and 126 were considered as low and high biofilm producers, respectively. Biofilm production by C. albicans was significantly lower than that by non-albicans isolates and was most frequently observed in C. tropicalis. Biofilm production was more frequent among bloodstream isolates than other clinical sources,in urine, the isolates displayed a peculiar distribution by presenting two distinct peaks, one containing biofilm-negative isolates and the other containing isolates with intense biofilm production. The numbers of tandem-repeat copies per allele were not associated with biofilm production, suggesting the evolvement of other genetic determinants.

  20. 泌尿系感染假丝酵母菌的临床特点及耐药性分析%Clinical ditrilation and resistance of infection candida albicans in urinary tract infection

    Institute of Scientific and Technical Information of China (English)

    雷毅; 刘晓薇; 姚林霞; 张玉娟

    2015-01-01

    Objectives To investigate the clinical character and drug resistance of Candida albicans in urinary tract infection,and to provide recommodation for reasonable selection of antibiotics.Methods The related clinical datas,including drug sensitivity tests of Candida albicans infection in hospitalized urinary tract infection from Januany 2011 to December 2013,were analyzed retrospectively.Results A total of 268 strains of Candida albicans were isoloted from 1688 samples of urine culture form urinary tract infection patients specimen,accounted for 15.87%,most of Candida tropicalis them were (52.6%),Candida albicans was 61 strais (22.76%),candida krysei was 26 strais (9.70%),candida glabrata was 19 strais (7.09%),All Candida albicans strains revealed a highest susceptibility rate to amphoterien B according to drug sensitivity tests invitro.The drug resistant rate to 5-fluorocytosine 、fluconazole 、ITC caconazole were 38.43% 、76.49% 、73.88% 、74.25%.Conclusions Candida albicans is one of the most common pathogens proceed from urinary tract infection and should be further detected and its results will guide us to use drugs appropriately and prevent infection effectively in Clinic practice.%目的 了解泌尿系感染假丝酵母菌菌株分布及耐药现状,为临床合理选择抗菌药物提供依据.方法 回顾性调查2011年10月~ 2013年12月本院住院患者泌尿系发生假丝酵母菌感染的相关资料及药敏结果.结果 从送检的1688份泌尿系感染患者的尿培养标本中共分离268株假丝酵母菌,检出率为15.87%,菌种以热带假丝酵母菌为主,占52.6%,其次为白色假丝酵母菌61株,占22.76%,克柔假丝酵母菌26株,占9.70%,光滑假丝酵母菌为19株,占7.09%.所有菌株体外药敏实验对两性曲霉B100%敏感,对5-氟胞嘧啶、氟康唑、伊曲康唑、酮康唑的耐药率分别是38.43%、76.49%、73.88%、74.25%.结论 假丝酵母菌是泌尿系发生感染

  1. Melittin induces apoptotic features in Candida albicans

    Energy Technology Data Exchange (ETDEWEB)

    Park, Cana [School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, 1370 Sankyuk-dong, Puk-ku, Daegu 702-701 (Korea, Republic of); Lee, Dong Gun, E-mail: dglee222@knu.ac.kr [School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, 1370 Sankyuk-dong, Puk-ku, Daegu 702-701 (Korea, Republic of)

    2010-03-26

    Melittin is a well-known antimicrobial peptide with membrane-active mechanisms. In this study, it was found that Melittin exerted its antifungal effect via apoptosis. Candida albicans exposed to Melittin showed the increased reactive oxygen species (ROS) production, measured by DHR-123 staining. Fluorescence microscopy staining with FITC-annexin V, TUNEL and DAPI further confirmed diagnostic markers of yeast apoptosis including phosphatidylserine externalization, and DNA and nuclear fragmentation. The current study suggests that Melittin possesses an antifungal effect with another mechanism promoting apoptosis.

  2. Evaluation of a rapid immunochromatographic assay for identification of Candida albicans and Candida dubliniensis.

    Science.gov (United States)

    Marot-Leblond, Agnes; Grimaud, Linda; David, Sandrine; Sullivan, Derek J; Coleman, David C; Ponton, Jose; Robert, Raymond

    2004-11-01

    Candida dubliniensis was first established as a novel yeast species in 1995. It is particularly associated with recurrent episodes of oral candidosis in human immunodeficiency virus (HIV)-infected patients, but it has also been detected at other anatomical sites and at a low incidence level in non-HIV-infected patients. It shares so many phenotypic characteristics with C. albicans that it is easily misidentified as such. No rapid, simple, and commercial test that allows differentiation between C. dubliniensis and C. albicans has been developed, until now. Accurate species identification requires the use of genotype-based techniques that are not routinely available in most clinical microbiology diagnostic laboratories. The present study was designed to evaluate the efficiency of a new test (the immunochromatographic membrane [ICM] albi-dubli test; SR2B, Avrille, France) to differentiate between C. albicans and C. dubliniensis. The organisms evaluated were strains whose identities had previously been confirmed by PCR tests and freshly isolated clinical strains and included 58 C. albicans isolates, 60 C. dubliniensis isolates, and 82 isolates belonging to other species of yeast. The ICM albi-dubli test is based on the principle of immunochromatographic analysis and involves the use of two distinct monoclonal antibodies that recognize two unrelated epitopes expressed by both species or specific to only one species. The assay requires no complex instrumentation for analysis and can be recommended for routine use in clinical microbiology laboratories. Results are obtained within 2 h and 30 min and are easy to interpret. This evaluation demonstrated the good performance of this immunochromatographic test for C. albicans and C. dubliniensis isolated on Sabouraud dextrose agar, CHOROMagar Candida, and CandidaSelect, with sensitivities and specificities ranging from 93.1 to 100%. These parameters decreased, however, to 91.4% when the test was performed with yeast isolated

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

    International Nuclear Information System (INIS)

    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

  4. Neuroinflammation and structural injury of the fetal ovine brain following intra-amniotic Candida albicans exposure

    OpenAIRE

    Ophelders, Daan R. M. G.; Gussenhoven, Ruth; Lammens, Martin; Küsters, Benno; Kemp, Matthew W.; Newnham, John P; Payne, Matthew S.; Suhas G Kallapur; Jobe, Allan H.; Zimmermann, Luc J.; Boris W Kramer; Tim G A M Wolfs

    2016-01-01

    Background Intra-amniotic Candida albicans (C. Albicans) infection is associated with preterm birth and high morbidity and mortality rates. Survivors are prone to adverse neurodevelopmental outcomes. The mechanisms leading to these adverse neonatal brain outcomes remain largely unknown. To better understand the mechanisms underlying C. albicans-induced fetal brain injury, we studied immunological responses and structural changes of the fetal brain in a well-established translational ovine mod...

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

    Directory of Open Access Journals (Sweden)

    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.

  6. 脾虚小鼠伴口腔白念珠菌感染唾液中sIgA含量改变%sIga Level Changes In Saliva of Mice With Spleen Deficiency Infected With Candida Albicans

    Institute of Scientific and Technical Information of China (English)

    任平; 马贤德; 关洪全

    2012-01-01

    Objective:To determine saliva slgA content changes in saliva of mice with spleen deficiency infected with oral Candida albicans and the relationship between spleen deficiency and Candida albicans susceptibility. Methods: The animal model of spleen deficiency was prepared by irregular-feeding and overstrain, using a local method of inoculation to establish oral Candida albicans infection model. The number of living Candida albicans in saliva was tested, enzyme-linked immunosorbent assay (ELISA) was used to measure levels of slgA in saliva in each groups. Results: There were increased number of living Candida albicans in saliva of mice with spleen deficiency infected with oral Candida albicans. slgA in saliva was significantly lower than other groups (P<0.01). Conclusion: The mice with spleen deficiency has high susceptibility of oral Candida albicans.%目的:通过测定脾虚小鼠伴口腔白念珠茵感染后唾液中sIgA的含量变化,探讨脾虚小鼠与白念珠菌易感性的关系.方法:采用饮食失节加劳倦过度的复合因素制备脾虚小鼠模型,采用局部接种的方法于正常对照组以及脾虚小鼠建立口腔黏膜白念珠菌感染模型,检测小鼠唾液中活白念珠菌数,应用酶联免疫吸附法(ELISA)测定各组小鼠唾液中sIgA的含量.结果:脾虚伴口腔白念珠菌感染组小鼠的唾液中活白念珠菌数增高,唾液中sIgA含量明显低于其他各组(P<0.01).结论:小鼠在脾虚状态下对口腔白念珠菌的易感性增强.

  7. 医院内非白假丝酵母菌感染的病原学及危险因素研究%Etiology features and risk factors analysis of non-albicans candida infections in hospital

    Institute of Scientific and Technical Information of China (English)

    冯文莉; 王艳青; 杨静; 奚志琴; 贾晓强; 吴媛

    2010-01-01

    Objective To investigate the etiology features and relevant risk factors of non-albicans candida infections in hospital. Methods 256 patients of non-albicans candida infections admitted in the second hospital of shanxi medical university from April 2006 to March 2008 were enrolled in this investigation, and a prospective case-control study was executed on 256 cases of non-albicans candida infections and 1220 cases of non-fungal infections. The incidence and risk factors of non-albicans candida infections were analyzed by statistical software SPSS13.0. Results Candida glabrata was the most common reason of non - albicans candida infections (38. 28% ) , followed by candida krusei (37. 11% ), candida parapsilosis ( 12. 50% ), candida tropicalis (9. 77% ), candida lusitaniae (2. 34% ). Univariate analysis and multivariate logistic regression analysis showed that aging, length of stay, underlying disease, losing albumin, using prophylaxis antifungal drugs, using broad spectrum antibiotics, invasive examination and treatment ( such as total parenteral nutrition ( TPN ), invasive procedures, central venous catheters, hemodialysis and mechanical ventilation,et al. ) were the independent risk factors for non-albicans candida infections. Conclusions Non-albicans candida was the main of fungal infections in patients. To efficiently control the disease, it will be helpful by early diagnosis and treatment underlying diseases and commodities and using appropriate tools of examine and treatment methods.%目的 探讨住院患者非白假丝酵母菌感染的病原学特征以及发生的相关危险因素.方法 对2006年4月1日至2008年3月31日间住院的256例非白假丝酵母菌感染患者的病原学进行了研究;采用病例对照研究方法,对256例非白假丝酵母菌感染者和1220例无真菌感染者进行对比分析,应用SPSS13.0统计软件分析其发生的危险因素.结果 (1)从不同部位共分离出非白假丝酵母菌256

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

    Directory of Open Access Journals (Sweden)

    Alessandra da Silva Dantas

    2015-02-01

    Full Text Available 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.

  9. Study on pre-immunization with Bacillus Calmette-Guerin (BCG) on Candida albicans infection in mice%卡介苗免疫预防小鼠白色念珠菌感染的实验研究

    Institute of Scientific and Technical Information of China (English)

    李丽波; 王玉祥

    2009-01-01

    目的 探讨卡介苗(BCG)预先免疫对小鼠白色念珠菌感染的影响.方法 采用BCG或灭菌生理盐水皮内注射预先免疫2周,然后由尾静脉注射白色念珠菌进行攻击,观察小鼠死亡率及计算存活小鼠肾组织带菌量.结果 BCG免疫组存活时间长于生理盐水免疫组(P<0.01);存活小鼠肾组织菌落计数:BCG免疫组远少于省里盐水免疫组(P<0.01).结论 BCG对小鼠白色念珠菌感染具有很好的保护作用.%Objective To investigate the effect of preimmunization with Bacillus Calmette-Guerin (BCG) on Candida albicans infection in mice. Methods BCG or 0.9% sterile saline was injected intracutaneously to ICR mice for preimmunization for two weeks before inoculation of Candida albicans by vena caudalis injection, then mortality rate of mice was observed and Candida albicans in mice kidney was examined. Results Survival time in BCG preimmunization group was longer than that in 0.9% sterile saline group (P<0.01); colony count of Candida albicans in mice kidney in BCG preimmunization group was less than that in saline group (P < 0.01). Conclusions BCG pre-immunization has protective effect from Candida albicans infection in mice.

  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. 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......, growth and subsequent escape of C. albicans are blocked inside human neutrophils. According to our findings, this blockage in human neutrophils might be a result of higher levels of MPO activity and the presence of α-defensins. We therefore outline differences in antifungal immune defense between humans...

  12. Karyotyping of Candida albicans and Candida glabrata from patients with Candida sepsis.

    Science.gov (United States)

    Klempp-Selb, B; Rimek, D; Kappe, R

    2000-01-01

    The aim of this study was to determine the relatedness of Candida strains from patients suffering from Candida septicaemia by typing of Candida isolates from blood cultures and different body sites by pulsed field gel electrophoresis (PFGE using a contour-clamped homogenous electric field, CHEF). We studied 17 isolates of Candida albicans and 10 isolates of Candida glabrata from six patients. Four patients suffered from a C. albicans septicaemia, one patient from a C. glabrata septicaemia, and one patient had a mixed septicaemia with C. albicans and C. glabrata. Eight isolates from blood cultures were compared with 19 isolates of other sites (stool six, urine four, genital swab four, tip of central venous catheter three, tracheal secretion one, sputum one). PFGE typing resulted in 10 different patterns, four with C. albicans and six with C. glabrata. Five of the six patients had strains of identical PFGE patterns in the blood and at other sites. Seven isolates of a 58-year-old female with a C. glabrata septicaemia fell into five different PFGE patterns. However, they showed minor differences only, which may be due to chromosomal rearrangements within a single strain. Thus it appears, that the colonizing Candida strains were identical to the circulating strains in the bloodstream in at least five of six patients.

  13. Effect of tyrosol on adhesion of Candida albicans and Candida glabrata to acrylic surfaces.

    Science.gov (United States)

    Monteiro, Douglas Roberto; Feresin, Leonardo Perina; Arias, Laís Salomão; Barão, Valentim Adelino Ricardo; Barbosa, Debora Barros; Delbem, Alberto Carlos Botazzo

    2015-09-01

    The prevention of adhesion of Candida cells to acrylic surfaces can be regarded as an alternative to prevent denture stomatitis. The use of quorum sensing molecules, such as tyrosol, could potentially interfere with the adhesion process. Therefore, the aim of this study was to assess the effect of tyrosol on adhesion of single and mixed cultures of Candida albicans and Candida glabrata to acrylic resin surfaces. Tyrosol was diluted in each yeast inoculum (10(7) cells/ml in artificial saliva) at 25, 50, 100, and 200 mM. Then, each dilution was added to wells of 24-well plates containing the acrylic specimens, and the plates were incubated at 37°C for 2 h. After, the effect of tyrosol was determined by total biomass quantification, metabolic activity of the cells and colony-forming unit counting. Chlorhexidine gluconate (CHG) was used as a positive control. Data were analyzed using analysis of variance (ANOVA) and the Holm-Sidak post hoc test (α = 0.05). The results of total biomass quantification and metabolic activity revealed that the tyrosol promoted significant reductions (ranging from 22.32 to 86.16%) on single C. albicans and mixed cultures. Moreover, tyrosol at 200 mM and CHG significantly reduced (p Candida adhesion to acrylic resin, and further investigations are warranted to clarify its potential against Candida infections.

  14. 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.

  15. Activation and binding of C3 by Candida albicans.

    OpenAIRE

    Kozel, T R; Brown, R R; Pfrommer, G S

    1987-01-01

    Interaction with components of the complement system is an important aspect of the pathogenesis of infection by Candida albicans. The key role of C3 as an opsonic ligand and as an element in amplification of complement activation led us to examine several factors that influence the activation and binding of C3 cleavage fragments to the yeast. Activation and binding of C3 were determined by use of normal human serum containing 125I-labeled C3. Incubation of yeast-phase cells in 20% serum led t...

  16. Comparison of the hemolytic activity between Candida albicans and Candida glabrata isolate,in oral cavity of HIV-infected patients%HIV感染者口腔白色念珠菌和光滑念珠菌溶血性的比较

    Institute of Scientific and Technical Information of China (English)

    罗刚; 徐平平; 董俊英

    2011-01-01

    目的:探讨HIV感染者口腔白色念珠菌和光滑念珠菌分离株的溶血性,及其与宿主机体免疫力(用CD4细胞计数表示)的关系.方法:40株白色念珠菌和加株光滑念珠菌按单一感染或是否与光滑(白色)念珠菌混合感染及CD4细胞计数的高低进行分组,采用羊血培养基法检测其溶血活性,并进行组间比较.结果:40株白色念珠菌和40株光滑念珠菌溶血活性均为阳性(100%),且光滑念珠菌的溶血性高于白色念珠菌.结论:溶血性是念珠菌的重要毒力因子,HIV感染者口腔光滑念珠菌溶血性高于白色念珠菌.%Objective To investigate the hemolytic activity of Candida albican and Candida glabrata isolates in oral cavity of HIV-infected patients, and its relationship with the immunity of the patients. Methods Forty Candida albican and 40 Candida glabrata isolates were grouped by infection types and CD4 cell count. The hemolytic activity was measured by sugar-enriched sheep blood agar medium. Results The hemolytic activity of Candida glabrate was significantly higher than that of Candida albicans (P < 0.01). Conclusion Hemolytic activity is an important virulence factor of Candida. The hemolytic activity of Candida glabrata was higher than that of Candida albicans in oral cavity of HIV-infected patients.

  17. The persistence of multifocal colonisation by a single ABC genotype of Candida albicans may predict the transition from commensalism to infection

    Directory of Open Access Journals (Sweden)

    Guilherme Maranhão Chaves

    2012-03-01

    Full Text Available Candida albicans is a common member of the human microbiota and may cause invasive disease in susceptible populations. Several risk factors have been proposed for candidaemia acquisition. Previous Candida multifocal colonisation among hospitalised patients may be crucial for the successful establishment of candidaemia. Nevertheless, it is still not clear whether the persistence or replacement of a single clone of C. albicans in multiple anatomical sites of the organism may represent an additional risk for candidaemia acquisition. Therefore, we prospectively evaluated the dynamics of the colonising strains of C. albicans for two groups of seven critically ill patients: group I included patients colonised by C. albicans in multiple sites who did not develop candidaemia and group II included patients who were colonised and who developed candidaemia. ABC and microsatellite genotyping of 51 strains of C. albicans revealed that patients who did not develop candidaemia were multiply colonised by at least two ABC genotypes of C. albicans, whereas candidaemic patients had highly related microsatellites and the same ABC genotype in colonising and bloodstream isolates that were probably present in different body sites before the onset of candidaemia.

  18. In vivo Models for Candida Albicans Biofilms Study

    Directory of Open Access Journals (Sweden)

    Wenrui Gu

    2016-03-01

    Full Text Available Biofilm is a common mode of fungal growth in clinical infection. In the mode of biofilm, Candida albicans tends to display high resistance to body immunity and antimicrobial agents, which has a significant impact on mortality. Biofilm models are essential tools to better understand the mechanisms of formation and resistance. Compared to in vitro models, in vivo models can better take into account the host immune system and are indispensable for the study of medical device related infection. The aim of this review is to summarize information related to the reported in vivo models of C. albicans biofilms, analyze the operating process and application of them, and compare their advantages and limitations. A literature search was performed from databases in Medline (PubMed, Web of Science, Science Direct, and Google scholar by applying some related search terms. The articles related to agriculture, ecology, and synthetic work and those using languages other than English have been excluded. The bibliographies of papers relating to the review subject were also searched for further relevant references. According to the common sites of C. albicans infection; three kinds of in vivo models are discussed in this review: oral mucosa model, vaginal mucosa model and implanted catheter model. The former two models can demonstrate the structure and composition of biofilms growing on the mucosa, and implanted catheter model represents different kinds of medical devices. To expedite the success of new treatments of infection, further refinement of in vivo models is an urgent need.

  19. Compressed moss patients saliva and candida albicans infection correlation research%扁平苔藓患者唾液与白色念珠菌感染相关性研究

    Institute of Scientific and Technical Information of China (English)

    朱建华; 苏丹; 赵千宁; 佟玮玮; 刘继光

    2015-01-01

    目的:探讨OLP患者唾液流量和pH值的变化与OLP患者感染白色念珠菌的相关性,并对其作为感染白色念珠菌的风险评估。方法:研究对象分为OLP糜烂组、OLP非糜烂组和正常对照组,每组20人。收集无刺激唾液,检测唾液流量与唾液pH,通过科玛嘉显色培养基显色培养唾液,对结果进行统计分析。结果:OLP糜烂组与正常对照组的唾液样本中白色念珠菌的表达差异有统计学意义,OLP糜烂组唾液流量对OLP非糜烂组和健康对照组的差异有统计学意义。结论:OLP患者唾液流量与白色念珠菌感染成负相关。OLP患者唾液流量可以作为评估OLP患者感染白色念珠菌风险的指标。%Objective:to investigate the OLP patients saliva flow rate and the change of pH value and the correlation of OLP patients infected with candida albicans. And study saliva flow as oral cavity compressed moss OLP patients infected with candida albicans risk assessment. Method:the research object is divided into OLP erosion and erosion group and nor-mal control group,each group of 20 people. After collecting saliva flow saliva and saliva pH measurement,by families,ma jia chromogenic medium color culture saliva,statistical analysis of the results. Result:complete the saliva pH value,the number of traffic and candida albicans colonies measurement,statistical results for OLP erosion group and normal control group the saliva samples of candida albicans expression difference was statistically significant,debaucjed of OLP saliva flow of OLP erosion group and healthy control group the difference was statistically significant. Conclusion:patients with oral cavity compressed moss saliva flow negative correlation with candida albicans infection. OLP patients saliva flow can be used as evaluating the risks of OLP patients infected with candida albicans.

  20. Expression of Candida Albicans Secreted Aspartyl Proteinase in Acute Vaginal Candidiasis

    Institute of Scientific and Technical Information of China (English)

    LIN Nengxing; FENG Jing; TU Yating; FENG Aiping

    2007-01-01

    In order to analyze the in vivo expression of Candida albicans secreted aspartyl proteinases (SAP) in human vaginal infection, the vaginal secretion from 29 human subjects was collected by vaginal swab, and the expression of SAP1-SAP6 was detected by reverse-transcriptase polymerase chain reaction using specific primer sets. It was found that Sap2 and Sap5 were the most common genes expressed during infection; Sap3 and Sap4 were detected in all subjects and all 6 SAP genes were simultaneously expressed in some patients with vaginal candidiasis. It was suggested that the SAP family is expressed by Candida albicans during infection in human and that Candida albicans infection is associated with the differential expression of individual SAP genes which may be involved in the pathogenesis of vaginal candidiasis.

  1. Establishment and evaluation of invasive Candida albicans infection model in mice%侵袭性白念珠菌小鼠感染模型的建立与评估

    Institute of Scientific and Technical Information of China (English)

    杜发娅; 阎澜; 姜远英; 徐贵丽

    2014-01-01

    目的:建立侵袭性白念珠菌小鼠感染模型。方法体外通过菌丝生长实验评价白念珠菌的毒力大小,通过尾静脉注射白念珠菌菌悬液感染小鼠后,观察小鼠生存时间,评价白念珠菌体内毒力大小;以感染后7 d 内小鼠100%死亡为标准,建立了侵袭性白念珠菌小鼠感染模型,对感染小鼠进行氟康唑治疗效果评价。结果白念珠菌体外毒力与体内毒力一致,4种培养基中菌丝均生长良好的菌株,体内感染小鼠后,小鼠生存率也最低;感染模型中,氟康唑对敏感白念珠菌的治疗效果强于对氟康唑耐药白念珠菌(P ﹤0.05)。结论建立的侵袭性白念珠菌感染模型可用于药物体内抗白念珠菌活性的筛选。%Objective To establish an invasive Candida albicans infection model in mice. Methods The virulence of Candida albicans in vitro was evaluated by means of mycelial growth experiment,while that in vivo was evaluated through the mouse infection model;an aliquot of culture containing Candida albicans with 5 × 105 CFU was injected into each mouse through the tail vein and the survival time of the infected mice was observed. 100% death of the mice within 7 days of infection was used as the successful establishment of the infection model;fluconazole was applied to the infected mice and the effect on the infection of Candida albicans was evaluated as well. Results Candida albicans had the same virulence in vitro and in vivo;strains were well inducted in the 4 hyphal induction media;the survival rate of the infected mice was very low;fluconazole was more effective on Candida albicans sensitive to it than on those resistant to it( P ﹤ 0. 05). Conclusions Invasive Candida albicans infection model in mice is applicable for drug screening of anti-Candida albicans activity in vivo.

  2. Establishment and evaluation of invasive Candida albicans infection model in mice%侵袭性白念珠菌小鼠感染模型的建立与评估

    Institute of Scientific and Technical Information of China (English)

    杜发娅; 阎澜; 姜远英; 徐贵丽

    2014-01-01

    Objective To establish an invasive Candida albicans infection model in mice. Methods The virulence of Candida albicans in vitro was evaluated by means of mycelial growth experiment,while that in vivo was evaluated through the mouse infection model;an aliquot of culture containing Candida albicans with 5 × 105 CFU was injected into each mouse through the tail vein and the survival time of the infected mice was observed. 100% death of the mice within 7 days of infection was used as the successful establishment of the infection model;fluconazole was applied to the infected mice and the effect on the infection of Candida albicans was evaluated as well. Results Candida albicans had the same virulence in vitro and in vivo;strains were well inducted in the 4 hyphal induction media;the survival rate of the infected mice was very low;fluconazole was more effective on Candida albicans sensitive to it than on those resistant to it( P ﹤ 0. 05). Conclusions Invasive Candida albicans infection model in mice is applicable for drug screening of anti-Candida albicans activity in vivo.%目的:建立侵袭性白念珠菌小鼠感染模型。方法体外通过菌丝生长实验评价白念珠菌的毒力大小,通过尾静脉注射白念珠菌菌悬液感染小鼠后,观察小鼠生存时间,评价白念珠菌体内毒力大小;以感染后7 d 内小鼠100%死亡为标准,建立了侵袭性白念珠菌小鼠感染模型,对感染小鼠进行氟康唑治疗效果评价。结果白念珠菌体外毒力与体内毒力一致,4种培养基中菌丝均生长良好的菌株,体内感染小鼠后,小鼠生存率也最低;感染模型中,氟康唑对敏感白念珠菌的治疗效果强于对氟康唑耐药白念珠菌(P ﹤0.05)。结论建立的侵袭性白念珠菌感染模型可用于药物体内抗白念珠菌活性的筛选。

  3. HIV aspartyl protease inhibitors as promising compounds against Candida albicans

    Institute of Scientific and Technical Information of China (English)

    André; Luis; Souza; dos; Santos

    2010-01-01

    Cells of Candida albicans(C.albicans) can invade humans and may lead to mucosal and skin infections or to deep-seated my coses of almost all inner organs,especially in immunocompromised patients.In this context,both the host immune status and the ability of C.albicans to modulate the expression of its virulence factors are relevant aspects that drive the candidal susceptibility or resistance;in this last case,culminating in the establishment of successful infection knownas candidiasis.C.albicans possesses a potent arma-mentarium consisting of several virulence moleculesthat help the fungal cells to escape of the host immuneresponses.There is no doubt that the secretion of aspartyl-type proteases,designated as Saps,are one of the major virulence attributes produced by C.albicans cells,since these hydrolytic enzymes participate in a wide range of fungal physiological processes as well as in different facets of the fungal-host interactions.For these reasons,Saps clearly hold promise as new potential drug targets.Corroborating this hypothesis,the introduction of new anti-human immunodeficiency virus drugs of the as party l protease inhibitor-type(HIV PIs) have emerged as new agents for the inhibition of Saps.The introduction of HIV PIs has revolutionized the treatment of HIV disease,reducing opportunistic infections,especially candidiasis.The attenuation of candidal infections in HIV-infected individuals might not solely have resulted from improved immunological status,but also as a result of direct inhibition of C.albicans Saps.In this article,we review updates on the beneficial effects of HIV PIs against the human fungal pathogen C.albicans,focusing on the effects of these compounds on Sap activity,growth behavior,morphological architecture,cellular differentiation,fungal adhesion to animal cells and abiotic materials,modulation of virulence factors,experimental candidiasis infection,and their synergistic actions with classical antifungal agents.

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Study of Candida Albicans Vaginitis Model in Kunming Mice

    Institute of Scientific and Technical Information of China (English)

    CHEN Zhuo; KONG Xiaofeng

    2007-01-01

    The model of vaginal candidiasis in Kunming mice was constructed in order to search for the optima construction conditions and provide an economic animal model of Candida albicans (C.albicans) vaginitis. Estrogen benzoate (E2) was given to mice at different concentrations ranging from 0.0 to 0.05 mg/mouse (4 levels) beginning 72 h prior to vaginal inoculation, then mice were inoculated intravaginally with various concentrations of stationary-phase C. albicans blastoconidia (ATCC90028) (5 levels) in 20 μL of phosphate-buffered saline (PBS) in each F2 level. General state,scores of genital pathology, the hyphae and vaginal fungal burden (CFU) in vaginal lavage fluid, the hydrops rate of uterus and vaginal tissues for pathological section in mice were observed and obtained at day 2, 4, 7, 14 and 21 after inoculation. The results showed the infection rate in mice was related to the dosage of E2 and concentration of C. albicans blastoconidia. Additionally there was better cross-effect between the two treated factors. The infection rate was about 80% on the day 4,and could reach 100% on the day 7 until the end of experiment after inoculated intravaginally in groups of E2I3, E2 0.025 mg/mouse injected hypodermically and inoculated intravaginally with 5×104 C. albicans blastoconidia, and large amount of hyphae and blastoconidia could be observe in superficial layer tissue and canal of vaginal by PAS. From the results in our experiment it was concluded that E2I3 was the optima construction condition in kunming mice.

  7. Sampling of Candida albicans and Candida tropicalis by Langerin-positive dendritic cells in mouse Peyer's patches.

    Science.gov (United States)

    De Jesus, Magdia; Rodriguez, Adam E; Yagita, Hideo; Ostroff, Gary R; Mantis, Nicholas J

    2015-11-01

    Members of the Candida genus, including C. albicans and C. tropicalis are opportunistic fungal pathogens that are increasingly associated with gastrointestinal infections and inflammatory bowel diseases. In healthy populations, however, C. albicans and C. tropicalis are considered benign members of the mycobiome, and are presumably kept in check by the mucosal immune system. In this study, we demonstrate in mice that C. albicans and C. tropicalis are sampled by Peyer's patch (PP) dendritic cells (DCs). Uptake into gut-associated lymphoid tissues occurred rapidly and was at least partly M cell-dependent. C. albicans and C. tropicalis preferentially localized in (and persisted within) a recently identified sub- population of Peyer's patch DCs distinguished by their expression of the C-type lectin receptor, Langerin. This study is the first to identify a subset of PP DCs capable of sampling Candida species.

  8. The impact of intestinal microbiota imbalances on susceptibility to invasive Candida albicans infection in SCID mice%SCID小鼠肠道菌群失调对深部白色念珠菌感染的影响研究

    Institute of Scientific and Technical Information of China (English)

    王飞玲; 陈楠; 董月娇; 陈瑜

    2012-01-01

    Objective To establish a severe combined immunodeficiency (SCID) mice model for invasive Candida albicans infection and study the relationship between imbalances of the intestinal microbiota and susceptibility to invasive Candida albicans infection. Method SCID mice were treated with 0. 125 g/250 mL of vancomycin in drinking water for 7 days and were deprived of food for 24 hours. Then the mice were inoculated with 0.1 mL 1.5 ×109 or 1.5 ×105 CFU of Candida albicans by intragastric gavage. After the invasive Candida albicans infection model of SCID mice was established, death of the SCID mice were closely observed. Total number of intestinal bacteria were measured by real-time PCR using 16S rRNA gene primers; alterations of diversity of the intestinal microbiota were rapidly identified with matrix-assisted laser desorption ionization time-of-flight mass spectrometry; the pathological changes of intestinal mucosa were observed by scanning transmission e-lectron microscope (SEM). Result Vancomycin caused the imbalance of intestinal microbiota and damage to intestinal mucosa. The Candida albicans attack had increased the damage of intestinal mucosa and promoted the occurrence of Candida albicans translocations after intestinal microbiota imbalance was induced. Conclusion The disruption of the intestinal microbiota alters the host susceptibility to Candida albicans infection and the integrity of intestinal mucosa may be also involved in the process of Candida albicans invasive infection.%目的 建立重度联合免疫缺陷(SCID)小鼠白色念珠菌感染模型,探讨肠道菌群失调与深部白色念珠菌感染的联系.方法 SCID小鼠随机口服万古霉素水溶液7d,饥饿24h后给予白色念珠菌灌胃,建立小鼠白色念珠菌感染模型,观察小鼠死亡情况.荧光定量PCR检测肠道细菌总量、基质辅助激光解析电离飞行时间质谱仪鉴定肠道菌群种类,并应用扫描电镜观察肠壁黏膜组

  9. Hydrophobic interaction in Candida albicans and Candida tropicalis adherence to various denture base resin materials.

    OpenAIRE

    Minagi, S; Miyake, Y; Inagaki, K; Tsuru, H; Suginaka, H

    1985-01-01

    The effects of hydrophobicities of substrate surfaces on microbial adherence were examined by using Candida albicans and Candida tropicalis and 21 denture base resin materials. With increasing surface free energy of resin plates, increasing adherence of C. albicans and decreasing adherence of C. tropicalis were observed. The surface free energy of C. albicans is higher than that of all resin material surfaces, and C. tropicalis has surface free energy lower than that of all materials used. In...

  10. Postantifungal effect of caspofungin against the Candida albicans and Candida parapsilosis clades.

    Science.gov (United States)

    Gil-Alonso, Sandra; Jauregizar, Nerea; Eraso, Elena; Quindós, Guillermo

    2016-10-01

    Killing and postantifungal effects could be relevant for the selection of optimal dosing schedules. This study aims to compare time-kill and postantifungal effects with caspofungin on Candida albicans (C. albicans, Candida dubliniensis, Candida africana) and Candida parapsilosis (C. parapsilosis, Candida metapsilosis, Candida orthopsilosis) clades. In the postantifungal effect experiments, strains were exposed to caspofungin for 1 h at concentrations 0.12-8 μg/mL. Time-kill experiments were conducted at the same concentrations. Caspofungin exhibited a significant and prolonged postantifungal effect (>37 h) with 2 μg/mL against the most strains of C. albicans clade. Against the C. parapsilosis clade, the postantifungal effect was albicans, C. dubliniensis and C. metapsilosis.

  11. 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 expose...

  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)

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

    Science.gov (United States)

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

    2016-04-01

    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. PMID:26546567

  15. The effect of Streptococcus mutans and Candida glabrata on Candida albicans biofilms formed on different surfaces

    NARCIS (Netherlands)

    T. Pereira-Cenci; D.M. Deng; E.A. Kraneveld; E.M.M. Manders; A.A. Del Bel Cury; J.M. ten Cate; W. Crielaard

    2008-01-01

    Although Candida containing biofilms contribute to the development of oral candidosis, the characteristics of multi-species Candida biofilms and how oral bacteria modulate these biofilms is poorly understood. The aim of this study was to investigate interactions between Candida albicans and either C

  16. Terpenoids of plant origin inhibit morphogenesis, adhesion, and biofilm formation by Candida albicans.

    Science.gov (United States)

    Raut, Jayant S; Shinde, Ravikumar B; Chauhan, Nitin M; Karuppayil, S Mohan

    2013-01-01

    Biofilm-related infections caused by Candida albicans and associated drug resistant micro-organisms are serious problems for immunocompromised populations. Molecules which can prevent or remove biofilms are needed. Twenty-eight terpenoids of plant origin were analysed for their activity against growth, virulence attributes, and biofilms of C. albicans. Eighteen molecules exhibited minimum inhibitory concentrations of isopulegol, menthol, carvone, α-thujone, and farnesol exhibited biofilm-specific activity. Eight terpenoids were identified as inhibitors of mature biofilms. This study demonstrated the antibiofilm potential of terpenoids, which need to be further explored as therapeutic strategy against biofilm associated infections of C. albicans. PMID:23216018

  17. Evaluation of the Effects of Incubation Temperature and Ph On the Susceptibility of Candida Albicans Isolates to Ketoconazole Invitro

    OpenAIRE

    F Katiraee; Z Farahnejad; M Riazipoor; MH Yadegari; H Zarrinfar

    2006-01-01

    Introduction: Candidiasis, as an opportunistic infection, is caused by the Candida species. Although Candida albicans is classified in the body as an endogenic flora, it plays an important role in creating Candida related diseases. Candida vulvovaginitis in pregnant women, diabetes mellitus patients and those using multiple antibiotics and contraceptive drugs demonstrates the high resistance of the organism against conventional medication. On the other hand, recurrent vaginitis disintegrates ...

  18. Performance comparison of phenotypic and molecular methods for detection and differentiation of Candida albicans and Candida dubliniensis

    Directory of Open Access Journals (Sweden)

    Ahmad Suhail

    2012-09-01

    Full Text Available Abstract Background Candida albicans is the most pathogenic Candida species but shares many phenotypic features with Candida dubliniensis and may, therefore, be misidentified in clinical microbiology laboratories. Candidemia cases due to C. dubliniensis are increasingly being reported in recent years. Accurate identification is warranted since mortality rates are highest for C. albicans infections, however, C. dubliniensis has the propensity to develop resistance against azoles more easily. We developed a duplex PCR assay for rapid detection and differentiation of C. albicans from C. dubliniensis for resource-poor settings equipped with basic PCR technology and compared its performance with three phenotypic methods. Methods Duplex PCR was performed on 122 germ tube positive and 12 germ tube negative isolates of Candida species previously identified by assimilation profiles on Vitek 2 ID-YST system. Typical morphologic characteristics on simplified sunflower seed agar (SSA, and reaction with a commercial (Bichro-Dubli latex agglutination test were also performed. The assay was further applied on 239 clinical yeast and yeast-like fungi and results were confirmed by DNA sequencing of internal transcribed spacer (ITS region of rDNA. Results The results of duplex PCR assay for 122 germ tube positive and 12 germ tube negative isolates of Candida species were comparable to their identification by Vitek 2 ID-YST system, colony characteristics on SSA and latex agglutination test. Application of duplex PCR also correctly identified all 148 C. albicans and 50 C. dubliniensis strains among 239 yeast-like fungi. Conclusions The data show that both, duplex PCR and Bichro-Dubli are reliable tests for rapid (within few hours identification of clinical yeast isolates as C. dubliniensis or C. albicans. However, duplex PCR may be applied directly on clinical yeast isolates for their identification as C. dubliniensis or C. albicans as it does not require prior

  19. Specific induction of fibronectin binding activity by hemoglobin in Candida albicans grown in defined media.

    OpenAIRE

    Yan, S.; Nègre, E; Cashel, J A; Guo, N; Lyman, C A; Walsh, T J; Roberts, D D

    1996-01-01

    Fibronectin (FN) is a major component of host extracellular matrix that may play an important role in the initiation and dissemination of Candida albicans infections. Expression of FN binding requires growth of C albicans blastoconidia in complex medium, and the regulation of FN receptor expression is poorly understood. We now demonstrate that hemoglobin is a potent and specific inducer of FN receptor expression and describe a defined medium supplemented with hemoglobin that greatly and stabl...

  20. Passage through the mammalian gut triggers a phenotypic switch that promotes Candida albicans commensalism

    OpenAIRE

    Pande, Kalyan; Chen, Changbin; Noble, Suzanne M.

    2013-01-01

    Among ~5,000,000 fungal species, 1 Candida albicans is exceptional in its lifelong association with humans, either within the gastrointestinal microbiome or as an invasive pathogen. 2 Opportunistic infections are generally ascribed to defective host immunity 3 but may require specific microbial programs. Here, we report that exposure of C. albicans to the mammalian gut triggers a developmental switch, driven by the Wor1 transcription factor, to a commensal cell type. Wor1 expression was previ...

  1. Does Candida albicans Als5p Amyloid Play a Role in Commensalism in Caenorhabditis elegans?

    OpenAIRE

    Bois, Michael; Singh, Sean; Samlalsingh, Alyssa; Lipke, Peter N.; Garcia, Melissa C.

    2013-01-01

    Candida albicans, a dimorphic fungus and an opportunistic pathogen, possesses a myriad of adherence factors, including members of the agglutinin-like sequence (Als) family of mannoproteins. The adhesin Als5p mediates adhesion to many substrates and is upregulated during commensal interactions but is downregulated during active C. albicans infections. An amyloid-forming core sequence at residues 325 to 331 is important for Als5p function, because a single-amino-acid substitution at position 32...

  2. MOLECULAR TYPING OF Candida albicans ISOLATES FROM HOSPITALIZED PATIENTS

    Directory of Open Access Journals (Sweden)

    Patricia de Souza Bonfim-Mendonca

    2013-12-01

    Full Text Available SUMMARY Introduction: The majority of nosocomial fungal infections are caused by Candida spp. where C. albicans is the species most commonly identified. Molecular methods are important tools for assessing the origin of the yeasts isolated in hospitals. Methods: This is a study on the genetic profifiles of 39 nosocomial clinical isolates of C. albicans using two typing methods: random amplifified polymorphic DNA (RAPD and microsatellite, two different primers for each technique were used. Results: RAPD provided 10 and 11 different profiles with values for SAB of 0.84 ± 0.126 and 0.88 ± 0.08 for primers M2 and P4, respectively. Microsatellite using two markers, CDC3 and HIS3, allowed the observation of six and seven different alleles, respectively, with combined discriminatory power of 0.91. Conclusions: Although genetic variability is clear, it was possible to identify high similarity, suggesting a common origin for at least a part of isolates. It is important to emphasize that common origin was proven from yeasts isolated from colonization (urine, catheter or endotracheal secretions and blood culture from the same patient, indicating that the candidemia must have started from a site of colonization. The combination of RAPD and microsatellite provides a quick and efficient analysis for investigation of similarity among nosocomial isolates of C. albicans.

  3. Thrush and Other Candida Infections

    Science.gov (United States)

    ... Text Size Email Print Share Thrush and Other Candida Infections Page Content Article Body The fungus Candida is ... thrush, frequently occurs in infants and toddlers. If Candida infections become chronic or occur in the mouth of ...

  4. Relationship between salivary flow rates and Candida albicans counts.

    Science.gov (United States)

    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 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.

  5. 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

  6. Chlorhexidine markedly potentiates the oxidants scavenging abilities of Candida albicans.

    Science.gov (United States)

    Ginsburg, I; Koren, E; Feuerstein, O; Zogakis, I P; Shalish, M; Gorelik, S

    2015-10-01

    The oxidant scavenging ability (OSA) of catalase-rich Candida albicans is markedly enhanced by chlorhexidine digluconate (CHX), polymyxin B, the bile salt ursodeoxycholate and by lysophosphatidylcholine, which all act as detergents facilitating the penetration of oxidants and their intracellular decomposition. Quantifications of the OSA of Candida albicans were measured by a highly sensitive luminol-dependent chemiluminescence assay and by the Thurman's assay, to quantify hydrogen peroxide (H2O2). The OSA enhancing activity by CHX depends to some extent on the media on which candida grew. The OSA of candida treated by CHX was modulated by whole human saliva, red blood cells, lysozyme, cationic peptides and by polyphenols. Concentrations of CHX, which killed over 95 % of Candida albicans cells, did not affect the cells' abilities to scavenge reactive oxygen species (ROS). The OSA of Candida cells treated by CHX is highly refractory to H2O2 (50 mM) but is strongly inhibited by hypochlorous acid, lecithin, trypan blue and by heparin. We speculate that similarly to catalase-rich red blood cells, Candida albicans and additional catalase-rich microbiota may also have the ability to scavenge oxidants and thus can protect catalase-negative anaerobes and facultative anaerobes cariogenic streptococci against peroxide and thus secure their survival in the oral cavity.

  7. 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.

  8. Experimental Study of the Effect of Specific IgY on Preventing Burned Rats from Secondary Infection of Candida Albicans%特异性IgY对烧伤鼠继发感染白念珠菌预防作用的实验研究

    Institute of Scientific and Technical Information of China (English)

    傅颖媛; 曹勇

    2000-01-01

    Objective: To investigate the effect of specific IgY on preventing burned rats from secondary infection of candida albicans. Method: The specific IgY against candida albicans was extracted from the yolk of eggs laid by the hens immunized by candida albicans isolated from burned patients with secondary infection of candida albicans. Burned rats infected with candida albicans were divided into 2 groups. Rats in one group were treated with IgY and rats in the control group were treated with saline. Results: Compared with the control group, the specific IgY was effective for preventing secondary infection of candida albicans in rats. The difference between the two groups was statistically significant. Conclusion: Specific IgY is effective for preventing burned rats from secondary infection of candida albicans.%目的:探索白念珠菌特异性IgY对烧伤鼠继发感染白念珠菌的预防作用。方法:自烧伤继发感染白念珠菌病人创面分离出的白念珠菌免疫蛋鸡,并将从该鸡产的蛋中分离出提取的特异性IgY用于烧伤感染白念珠菌大鼠。结果:特异性IgY能明显抑制烧伤鼠创面(痂下组织)继发感染白念珠菌,与对照组比有显著性差异。结论:白念珠菌特异性IgY有助于烧伤鼠预防白念珠菌的继发感染

  9. Candida albicans and Enterococcus faecalis in the gut: Synergy in commensalism?

    OpenAIRE

    Garsin, Danielle A.; Michael C Lorenz

    2013-01-01

    The fungus Candida albicans and the gram-positive bacterium Enterococcus faecalis are both normal residents of the human gut microbiome and cause opportunistic disseminated infections in immunocompromised individuals. Using a nematode infection model, we recently showed that co-infection resulted in less pathology and less mortality than infection with either species alone and this was partly explained by an interkingdom signaling event in which a bacterial-derived product inhibits hyphal mor...

  10. Growth of Candida albicans cells on the physiologically relevant carbon source lactate affects their recognition and phagocytosis by immune cells

    NARCIS (Netherlands)

    Ene, I.V.; Cheng, S.C.; Netea, M.G.; Brown, A.J.

    2013-01-01

    Candida albicans is a normal resident of the human gastrointestinal and urogenital tracts and also a prevalent fungal pathogen. During both commensalism and infection, it must match the immunological defenses of its host while adapting to environmental cues and the local nutrient status. C. albicans

  11. Antimicrobial blue light inactivation of Candida albicans: In vitro and in vivo studies.

    Science.gov (United States)

    Zhang, Yunsong; Zhu, Yingbo; Chen, Jia; Wang, Yucheng; Sherwood, Margaret E; Murray, Clinton K; Vrahas, Mark S; Hooper, David C; Hamblin, Michael R; Dai, Tianhong

    2016-07-01

    Fungal infections are a common cause of morbidity, mortality and cost in critical care populations. The increasing emergence of antimicrobial resistance necessitates the development of new therapeutic approaches for fungal infections. In the present study, we investigated the effectiveness of an innovative approach, antimicrobial blue light (aBL), for inactivation of Candida albicans in vitro and in infected mouse burns. A bioluminescent strain of C. albicans was used. The susceptibilities to aBL (415 nm) were compared between C. albicans and human keratinocytes. The potential development of aBL resistance by C. albicans was investigated via 10 serial passages of C. albicans on aBL exposure. For the animal study, a mouse model of thermal burn infected with the bioluminescent C. albicans strain was used. aBL was delivered to mouse burns approximately 12 h after fungal inoculation. Bioluminescence imaging was performed to monitor in real time the extent of infection in mice. The results obtained from the studies demonstrated that C. albicans was approximately 42-fold more susceptible to aBL than human keratinocytes. Serial passaging of C. albicans on aBL exposure implied a tendency of reduced aBL susceptibility of C. albicans with increasing numbers of passages; however, no statistically significant difference was observed in the post-aBL survival rate of C. albicans between the first and the last passage (P>0.05). A single exposure of 432 J/cm(2) aBL reduced the fungal burden in infected mouse burns by 1.75-log10 (P=0.015). Taken together, our findings suggest aBL is a potential therapeutic for C. albicans infections. PMID:26909654

  12. Differential adaptation of Candida albicans in vivo modulates immune recognition by dectin-1

    NARCIS (Netherlands)

    Marakalala, M.J.; Vautier, S.; Potrykus, J.; Walker, L.A.; Shepardson, K.M.; Hopke, A.; Mora-Montes, H.M.; Kerrigan, A.; Netea, M.G.; Murray, G.I.; MacCallum, D.M.; Wheeler, R.; Munro, C.A.; Gow, N.A.; Cramer, R.A.; Brown, A.J.; Brown, G.D.

    2013-01-01

    The beta-glucan receptor Dectin-1 is a member of the C-type lectin family and functions as an innate pattern recognition receptor in antifungal immunity. In both mouse and man, Dectin-1 has been found to play an essential role in controlling infections with Candida albicans, a normally commensal fun

  13. Beyond the wall: Candida albicans secret(e)s to survive

    NARCIS (Netherlands)

    A.G. Sorgo; C.J. Heilmann; S. Brul; C.G. de Koster; F.M. Klis

    2013-01-01

    The opportunistic fungal pathogen Candida albicans occupies various niches of the human body such as the skin and the mucosal surfaces of the gastrointestinal and urogenital tracts. It can also enter the blood stream and cause deadly, systemic infections, especially in immunocompromised patients, bu

  14. Human Epithelial Cells Discriminate between Commensal and Pathogenic Interactions with Candida albicans.

    Science.gov (United States)

    Rast, Timothy J; Kullas, Amy L; Southern, Peter J; Davis, Dana A

    2016-01-01

    The commensal fungus, Candida albicans, can cause life-threatening infections in at risk individuals. C. albicans colonizes mucosal surfaces of most people, adhering to and interacting with epithelial cells. At low concentrations, C. albicans is not pathogenic nor does it cause epithelial cell damage in vitro; at high concentrations, C. albicans causes mucosal infections and kills epithelial cells in vitro. Here we show that while there are quantitative dose-dependent differences in exposed epithelial cell populations, these reflect a fundamental qualitative difference in host cell response to C. albicans. Using transcriptional profiling experiments and real time PCR, we found that wild-type C. albicans induce dose-dependent responses from a FaDu epithelial cell line. However, real time PCR and Western blot analysis using a high dose of various C. albicans strains demonstrated that these dose-dependent responses are associated with ability to promote host cell damage. Our studies support the idea that epithelial cells play a key role in the immune system by monitoring the microbial community at mucosal surfaces and initiating defensive responses when this community is dysfunctional. This places epithelial cells at a pivotal position in the interaction with C. albicans as epithelial cells themselves promote C. albicans stimulated damage.

  15. Toll-like receptor 2 suppresses immunity against Candida albicans through induction of IL-10 and regulatory T cells.

    NARCIS (Netherlands)

    Netea, M.G.; Sutmuller, R.P.M.; Hermann, C.; Graaf, C.A.A. van der; Meer, J.W.M. van der; Krieken, J.H.J.M. van; Hartung, T.; Adema, G.J.; Kullberg, B.J.

    2004-01-01

    Toll-like receptor (TLR) 2 and TLR4 play a pivotal role in recognition of Candida albicans. We demonstrate that TLR2(-/-) mice are more resistant to disseminated Candida infection, and this is associated with increased chemotaxis and enhanced candidacidal capacity of TLR2(-/-) macrophages. Although

  16. 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...

  17. Blood group glycolipids as epithelial cell receptors for Candida albicans.

    OpenAIRE

    Cameron, B J; Douglas, L J

    1996-01-01

    The role of glycosphingolipids as possible epithelial cell receptors for Candida albicans was examined by investigating the binding of biotinylated yeasts to lipids extracted from human buccal epithelial cells and separated on thin-layer chromatograms. Binding was visualized by the addition of 125I-streptavidin followed by autoradiography. Five C. albicans strains thought from earlier work to have a requirement for fucose-containing receptors all bound to the same three components in the lipi...

  18. Improved assay for surface hydrophobic avidity of Candida albicans cells.

    OpenAIRE

    Hazen, K C; LeMelle, W G

    1990-01-01

    A simple method that distinguishes among hydrophobic avidity levels of highly hydrophobic isolates of the pathogenic fungus Candida albicans is described. This method involves mixing polystyrene microspheres at different concentrations with a constant concentration of yeast cells and plotting the data in accordance with the Langmuir isotherm equation. A 10-fold difference between the C. albicans isolates with the lowest and highest avidity (KH) values was found. This method may also demonstra...

  19. Candida albicans specializations for iron homeostasis: from commensalism to virulence

    OpenAIRE

    Noble, Suzanne

    2013-01-01

    Candida albicans is a fungal commensal-pathogen that persistently associates with its mammalian hosts. Between the commensal and pathogenic lifestyles, this microorganism inhabits host niches that differ markedly in the levels of bioavailable iron. A number of recent studies have exposed C. albicans specializations for acquiring iron from specific host molecules in regions where iron is scarce, while also defending against iron-related toxicity in regions where iron occurs in surfeit. Togethe...

  20. Denture Stomatitis and Candida Albicans in Iranian Population: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Mahmood Moosazadeh

    2016-09-01

    Full Text Available Statement of the Problem: Denture stomatitis is the common form of oral candidiasis, which is seen in the form of diffused inflammation in the areas covered by dentures. Many primary studies report the prevalence of denture stomatitis and candida albicans among patients in the Iranian population; therefore, using meta-analysis is valuable for health policy makers. Purpose: The purpose of the present study is to determine the prevalence of denture stomatitis and candida albicans in Iran. Materials and Method: Using relevant keywords, national and international databases were searched. After limiting the search strategy and deleting the duplicates, the remaining papers were screened by examining the title and abstract. In order to increase the sensitivity of search reference lists of papers were examined. Finally the index of heterogeneity between studies was defined using Cochran test (Q and I-squared (I2. According to heterogeneity, the random effects model was used to estimate the prevalence of denture stomatitis and candida albicans in Iran. Result: The prevalence of denture stomatitis in 12 studies, and the prevalence of candida albicans in patients with denture stomatitis have been reported in 6 studies. The number of sample under investigated and its age range among primary studies included meta- analysis was 2271 individuals and 32.7 till 87.5 years respectively. The prevalence of denture stomatitis in preliminary studies imported to a meta-analysis varied from 1.9% to 54.6%, and its rate in Iran using the meta-analysis was estimated 28.9 % (CI 95%: 18.2-39.6. Also the overall prevalence of candida albicans in patients with denture stomatitis in Iran was estimated 60.6% (CI 95%:50.1-71.2. Conclusion: This study showed that the prevalence of denture stomatitis and candida albicans among patient infected denture stomatitis is relatively significant in Iran.

  1. Case report: Candida zeylanoides infective endocarditis complicating infection with the human immunodeficiency virus.

    Science.gov (United States)

    Whitby, S; Madu, E C; Bronze, M S

    1996-09-01

    Despite the frequent occurrence of mucosal candidiasis in patients infected with HIV, systemic candidiasis is uncommon and usually associated with intravenous catheters, parenteral nutrition, or antibiotics and neutropenia. Most of the fungal isolates are usually Candida albicans, Candida tropicalis or Candida parapsilosis. The authors report a case of infective endocarditis due to Candida zeylanoides that occurred in a patient infected with HIV in the absence of the usual risk factors for systemic candidiasis.

  2. Correlation between virulence of Candida albicans mutants in mice and Galleria mellonella larvae.

    Science.gov (United States)

    Brennan, Marc; Thomas, David Y; Whiteway, Malcolm; Kavanagh, Kevin

    2002-10-11

    Candida albicans is a dimorphic human pathogen in which the yeast to hyphal switch may be an important factor in virulence in mammals. This pathogen has recently been shown to also kill insects such as the Greater Wax Moth Galleria mellonella when injected into the haemocoel of the insect larvae. We have investigated the effect of previously characterised C. albicans mutations that influence the yeast to hyphal transition on virulence in G. mellonella larvae. There is a good correlation between the virulence of these mutants in the insect host and the virulence measured through systemic infection of mice. Although the predominant cellular species detected in G. mellonella infections is the yeast form of C. albicans, mutations that influence the hyphal transition also reduce pathogenicity in the insect. The correlation with virulence measured in the mouse infection system suggests that Galleria may provide a convenient and inexpensive model for the in vivo screening of mutants of C. albicans. PMID:12381467

  3. Candida infection in HIV positive patients 1985-2007.

    Science.gov (United States)

    Traeder, Christian; Kowoll, Susann; Arastéh, Keikawus

    2008-09-01

    Infection with Candida species remains a major problem in HIV infected patients. The analysis of over 15,000 hospitalisations (1985-2007) in the AVK cohort shows an increasing incidence of non-albicans species in candida esophagitis. Although our analysis shows a decreasing incidence of opportunistic infections like PCP, cerebral toxoplasmosis and others since the introduction of highly active antiretroviral therapy the incidence of candida esophagitis remains as high as in the years before the HAART era. This observation might reflect the development of resistance against fluconazole and the selection of non-albicans species as a consequence of a long-term prophylactic treatment of HIV+ patients over years.

  4. Heat-shock protein 90 in Candida albicans

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Researches on Candidal heat-shock protein 90 (HSP90) in recent years are summarized.Candida albicans is a commensal pathogen in human and animals.In immunocompromised individuals it behaves as an opportunist pathogen,giving rise to superficial or systemic infections.Systemic candidosis is a common cause of death among immunocompromised and debilitated patients,in which the mortality is as high as 70%.HSP90 is now recognized as an immunodominant antigen in C.albicans and plays a key role in systemic candidosis as a molecular chaperone.The 47-ku peptide is the breakdown product of HSP90.Patients who has recovered from systemic candidosis produce high titre of antibodies to 47-ku antigen,whereas the fatal cases have little antibody or falling titres.The three commonest epitopes of candidal HSP90 have been mapped,epitopes C,B and H.Epitopes C and H are immunogenic.The antibody probes of both epitopes may be developed into a new serological test agents for systemic candidosis due to rather high specificity and sensitivity.The recent results establish HSP90 as an ATP-dependent chaperone that is involved in the folding of cell regulatory proteins and in the refolding of stress-denatured polypeptides.Some researches on fungal HSP90 and the treatment of patients with candidosis are reviewed as well.

  5. Molecular concordance of concurrent Candida albicans candidemia and candiduria.

    Science.gov (United States)

    Huang, Po-Yen; Hung, Min-Hui; Shie, Shian-Sen; Su, Lin-Hui; Chen, Ke-Yuan; Ye, Jung-Jr; Chiang, Ping-Cheng; Leu, Hsieh-Shong; Huang, Ching-Tai

    2013-07-01

    The significance of candiduria remains unclear. We correlated Candida albicans candidemia with candiduria by molecular genotyping. 33 pairs of concurrent blood and urine C. albicans isolates from 31 adult (≥ 18 years) were genotyped with infrequent-restriction-site PCR. The molecular concordance rates of three major genotypes were 100% for I, 82% for II, and 71% for III. The molecular concordance between concurrent C. albicans candidemia and candiduria was frequent. Our findings substantiate the importance of candiduria in appropriate clinical context as the majority of our patients were from intensive care units.

  6. Multilocus sequence typing confirms synonymy but highlights differences between Candida albicans and Candida stellatoidea.

    NARCIS (Netherlands)

    Jacobsen, M.D.; Boekhout, T.; Odds, F.C.

    2008-01-01

    We used multi-locus sequence typing (MLST) to investigate 35 yeast isolates representing the two genome-sequenced strains plus the type strain of Candida albicans, four isolates originally identified as Candida stellatoidea type I and 28 representing type strains of other species now regarded as syn

  7. Antimicrobial Photodynamic Inactivation Inhibits Candida albicans Virulence Factors and Reduces In Vivo Pathogenicity

    Science.gov (United States)

    Sabino, Caetano Padial; Fuchs, Beth Burgwyn; Tegos, George P.; Mylonakis, Eleftherios; Hamblin, Michael R.; Ribeiro, Martha Simões

    2013-01-01

    The objective of this study was to evaluate whether Candida albicans exhibits altered pathogenicity characteristics following sublethal antimicrobial photodynamic inactivation (APDI) and if such alterations are maintained in the daughter cells. C. albicans was exposed to sublethal APDI by using methylene blue (MB) as a photosensitizer (0.05 mM) combined with a GaAlAs diode laser (λ 660 nm, 75 mW/cm2, 9 to 27 J/cm2). In vitro, we evaluated APDI effects on C. albicans growth, germ tube formation, sensitivity to oxidative and osmotic stress, cell wall integrity, and fluconazole susceptibility. In vivo, we evaluated C. albicans pathogenicity with a mouse model of systemic infection. Animal survival was evaluated daily. Sublethal MB-mediated APDI reduced the growth rate and the ability of C. albicans to form germ tubes compared to untreated cells (P < 0.05). Survival of mice systemically infected with C. albicans pretreated with APDI was significantly increased compared to mice infected with untreated yeast (P < 0.05). APDI increased C. albicans sensitivity to sodium dodecyl sulfate, caffeine, and hydrogen peroxide. The MIC for fluconazole for C. albicans was also reduced following sublethal MB-mediated APDI. However, none of those pathogenic parameters was altered in daughter cells of C. albicans submitted to APDI. These data suggest that APDI may inhibit virulence factors and reduce in vivo pathogenicity of C. albicans. The absence of alterations in daughter cells indicates that APDI effects are transitory. The MIC reduction for fluconazole following APDI suggests that this antifungal could be combined with APDI to treat C. albicans infections. PMID:23129051

  8. Evaluation of Bichro-Dubli Fumouze to distinguish Candida dubliniensis from Candida albicans.

    Science.gov (United States)

    Sahand, Ismail H; Moragues, María D; Robert, Raymond; Quindós, Guillermo; Pontón, José

    2006-06-01

    We have evaluated the ability of the Bichro-Dubli Fumouze (Fumouze Diagnostics, Levallois-Perret, France) latex agglutination test to identify colonies of Candida dubliniensis grown on different media. The test was positive for 103 of 106 isolates of C. dubliniensis and negative for Candida albicans and other Candida species studied. The sensitivity and specificity of the test were 97.1% and 100%, respectively. The test is very rapid, simple, and reliable giving the same results independently of whether the colonies are grown previously on Sabouraud dextrose agar, CHROMagar Candida medium, Candida ID2 medium, or CHROMagar-Pal's medium. PMID:16529902

  9. 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.

  10. 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)

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

    OpenAIRE

    Sarah Kartimah Djajusman; Udijanto Tedjosasongko; Irmawati Irmawati

    2014-01-01

    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 sucros...

  12. Development of a membrane based detection of Candida albicans

    OpenAIRE

    Almeida, Catarina Guerreiro Silva de

    2015-01-01

    Tese de mestrado integrado em Engenharia Biomédica e Biofísica , apresentada à Universidade de Lisboa, através da Faculdade de Ciências, 2015 Candida é uma família de fungos, normalmente, presente na flora gastrointestinal, nos orgãos genitais, no sistema respiratório e na pele de pessoas saudáveis e, até determinada quantidade, não trazem nenhum risco. Apenas 17 espécies de Candida podem ser consideradas como patogénicas para o ser humano e, dentro deste grupo, Candida albicans é a esp...

  13. Antibiofilm activity of carboxymethyl chitosan on the biofilms of non-Candida albicans Candida species.

    Science.gov (United States)

    Tan, Yulong; Leonhard, Matthias; Moser, Doris; Schneider-Stickler, Berit

    2016-09-20

    Although most cases of candidiasis have been attributed to Candida albicans, non-C. albicans Candida species have been isolated in increasing numbers in patients. In this study, we determined the inhibition of carboxymethyl chitosan (CM-chitosan) on single and mixed species biofilm of non-albicans Candida species, including Candida tropicalis, Candida parapsilosis, Candida krusei and Candida glabrata. Biofilm by all tested species in microtiter plates were inhibited nearly 70%. CM-chitosan inhibited mixed species biofilm in microtiter plates and also on medical materials surfaces. To investigate the mechanism, the effect of CM-chitosan on cell viability and biofilm growth was employed. CM-chitosan inhibited Candida planktonic growth as well as adhesion. Further biofilm formation was inhibited with CM-chitosan added at 90min, 12h or 24h after biofilm initiation. CM-chitosan was not only able to inhibit the metabolic activity of Candida cells, but was also active upon the establishment and the development of biofilms.

  14. Antibiofilm activity of carboxymethyl chitosan on the biofilms of non-Candida albicans Candida species.

    Science.gov (United States)

    Tan, Yulong; Leonhard, Matthias; Moser, Doris; Schneider-Stickler, Berit

    2016-09-20

    Although most cases of candidiasis have been attributed to Candida albicans, non-C. albicans Candida species have been isolated in increasing numbers in patients. In this study, we determined the inhibition of carboxymethyl chitosan (CM-chitosan) on single and mixed species biofilm of non-albicans Candida species, including Candida tropicalis, Candida parapsilosis, Candida krusei and Candida glabrata. Biofilm by all tested species in microtiter plates were inhibited nearly 70%. CM-chitosan inhibited mixed species biofilm in microtiter plates and also on medical materials surfaces. To investigate the mechanism, the effect of CM-chitosan on cell viability and biofilm growth was employed. CM-chitosan inhibited Candida planktonic growth as well as adhesion. Further biofilm formation was inhibited with CM-chitosan added at 90min, 12h or 24h after biofilm initiation. CM-chitosan was not only able to inhibit the metabolic activity of Candida cells, but was also active upon the establishment and the development of biofilms. PMID:27261732

  15. Antimicrobial and Antibiofilm Activity of Chitosan on the Oral Pathogen Candida albicans

    Directory of Open Access Journals (Sweden)

    Eduardo Costa

    2014-12-01

    Full Text Available Oral candidiasis is particularly evident, not only in cancer patients receiving chemotherapy, but also in elderly people with xerostomy. In general, Candida is an opportunistic pathogen, causing infections in immunocompromised people and, in some cases, when the natural microbiota is altered. Chitosan, a natural derivative of chitin, is a polysaccharide that has been proven to possess a broad spectrum of antimicrobial activity that encompasses action against fungi, yeast and bacteria. While recent studies have revealed a significant antibiofilm activity upon several microorganisms, including C. albicans, little is known regarding the impact of chitosan upon the adhesive process or mature biofilms. With that in mind, the purpose of this work was to evaluate, in vitro, the capability of chitosan to inhibit C. albicans growth and biofilm formation. The results obtained showed that chitosan is capable of inhibiting C. albicans planktonic growth (HMW, 1 mg/mL; LMW, 3 mg/mL. Regarding biofilm growth, chitosan inhibited C. albicans adhesion (ca. 95%, biofilm formation (percentages above 90% and reduced mature biofilms by ca. 65% and dual species biofilms (C. albicans and S. mutans by ca. 70%. These results display the potential of this molecule to be used as an effective anti-Candida agent capable of acting upon C. albicans infections.

  16. Allium sativum (garlic) inhibits lipid synthesis by Candida albicans.

    OpenAIRE

    Adetumbi, M; Javor, G T; Lau, B H

    1986-01-01

    The effect of aqueous garlic extract on the macromolecular synthesis of Candida albicans was studied. Protein and nucleic acid syntheses were inhibited to the same extent as growth, but lipid synthesis was completely arrested. Blockage of lipid synthesis is likely an important component of the anticandidal activity of garlic.

  17. PERTUMBUHAN CANDIDA ALBICANS PADA PERMUKAAN POLIESTER EBP-2421

    Directory of Open Access Journals (Sweden)

    Widowati Siswomihardjo

    2015-08-01

    Full Text Available Acrylic resin has been the only polymeric material for denture base for many years. One of the requirements for an ideal polymeric denture base material. It should be resistant to bacterial growth. The growth of Candida albicans on the surface of dentures is a concern for many denture wearers. This organism often is associated with denture stomatitis. A preliminary study showed polyester EBP-2421, a polymeric material for statues can also be manipulated to denture base. This research examined the growth of Candida albicans on the surface of EBP-2421. Research was carried out on strips of polyester EBP-2421 and Selton acrylic resin. Strips were contaminated with Candida albicans for 24 hours. Examinations on polyester EBP-2421 and acrylic resin immersed in saliva significantly differ from the not immersed strips (p<0,05. The lowest frequency were Candida albicans adhered on stripes of polyester EBP-2421 immersed in saliva. This result related with the fact that polyester EBP-2421 has smoother surface topography than acrylic resin.

  18. Al-2 of Aggregatibacter actinomycetemcomitans inhibits Candida albicans biofilm formation

    NARCIS (Netherlands)

    Bachtiar, Endang W.; Bachtiar, Boy M.; Jarosz, Lucja M.; Amir, Lisa R.; Sunarto, Hari; Ganin, Hadas; Meijler, Michael M.; Krom, Bastiaan P.

    2014-01-01

    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 (Al

  19. Synergistic activity of rabbit granulocyte peptides against Candida albicans.

    OpenAIRE

    Lehrer, R I; Szklarek, D; Ganz, T; Selsted, M E

    1986-01-01

    Rabbit granulocytes contain six antimicrobial peptides that are structurally homologous to the human neutrophil "defensins." NP-5, a rabbit defensin, lacks significant activity against Candida albicans. Nevertheless, its addition to submicromolar concentrations of rabbit NP-1, NP-2, or NP-3a potentiates their candidacidal effect. Thus, granulocyte defensins can act synergistically against potential pathogens.

  20. Resistance of Candida albicans biofilms to antifungal agents in vitro.

    OpenAIRE

    Hawser, S. P.; Douglas, L J

    1995-01-01

    Biofilms formed by Candida albicans on small discs of catheter material were resistant to the action of five clinically important antifungal agents as determined by [3H]leucine incorporation and tetrazolium reduction assays. Fluconazole showed the greatest activity, and amphotericin B showed the least activity against biofilm cells. These findings were confirmed by scanning electron microscopy of the biofilms.

  1. Reduced virulence of Candida albicans mutants affected in multidrug resistance.

    OpenAIRE

    Becker, J. M.; Henry, L K; Jiang, W; Koltin, Y.

    1995-01-01

    Disruption of a multidrug resistance gene (CaMDR1) in Candida albicans resulted in mutant strains that colonized mouse kidneys to very high levels but were markedly reduced in their virulence. No obvious differences in several properties related to colonization and dissemination were noted among MDR+ or mdr- strains. These results suggest that specific fungal efflux pumps play a role in fungal pathogenicity.

  2. Clinical analysis of Candida albicans infection in acute exacerbations of Chronic obstructive pulmonary disease%慢性阻塞性肺疾病急性加重期白色念珠菌感染临床分析

    Institute of Scientific and Technical Information of China (English)

    段玉香; 赵美华; 高中度

    2010-01-01

    Objective To find out the risk factors in lung infection,clinical features and therapeutic of candida albicans infection in acute exacerbations of chronic obstructive pulmonary disease.Methods 50 cases of AECOPD with Candida albicans infection were retrospectively analyzed,comparing with 50 cases without fungal infection.The risk factors in lung infection,clinical features and therapeutic of Candida albicans infection were analyzed and calculated.The former for the test group,the latter as a control group.Results The average age of the patients in the test group,was 66.6 years old,75% of total cases were in the merger of consciousness,serum albumin lower than 28 g/L( 50% ),average usage time of antibiotics more than 14 days (75 % ),glucocorticoid was used significantly higher than control group (83.3%).Conclusion If the merger of consciousness,low serum albumin,antimicrobial drug use is too long,the glucocorticoids used in patients with AECOPD,candida albicans infection were increased,but the age and sex had no impactiou obviously.The patients with basic diseases such as diabetes,cardiovascular and cerebrovascular disease,cancer,malignancy or chronic renal insufficiency were combined with high rates of candida albicans infection.%目的 探讨慢性阻塞性肺疾病急性加重期(AECOPD)肺部白色念珠菌感染的易患因素、和治疗.方法 本文收集我科2007年1月至2009年12月住院治疗的AECOPD合并肺部真菌感染及未肺部真菌感染病例各50例,前者为试验组,后者为对照组,观察两组患者的易患因素和治疗情况.结果 试验组患者平均年龄66.6岁,75%合并意识障碍,50%血清白蛋白低于28g/L,75%抗菌素平均使用时间超过14 d,83.3%使用糖皮质激素明显高于对照组.结论 若AECOPD患者合并意识障碍、血清白蛋白低下、抗菌药物使用过长、使用糖皮质激素者则白色念珠菌染机会明显增多,与发病年龄及性别关系不明显,有糖尿病、及心脑血管

  3. Macrophage phagocytosis of Candida albicans. An in vitro study

    Directory of Open Access Journals (Sweden)

    WEINFELD Ilan

    1999-01-01

    Full Text Available Considering the role of macrophages in relation to fungi and the various utilized methodologies, the authors established an in vitro model to evaluate macrophage phagocytosis of Candida albicans. Activated macrophages were obtained from the peritoneal cavity of isogenic mice (A/Sn. Two different strains of Candida albicans serotype A and serotype B with different levels of pathogenicity in vivo and other similar characteristics were utilized in the study. Several microscopic fields containing about 200 macrophages were counted. The percentage of macrophages phagocytizing at least one viable or nonviable yeast cell determined an average number of phagocytized yeasts. Neutral red and fluorescein diacetate plus ethidium bromide were used for staining. It is possible to conclude that this is an efficient model related to the used methodology. The average number of yeasts in both strains were similar when inside macrophages, and there was a higher percentage of C. albicans serotype A phagocytosis, which was not experimentally pathogenic in vivo.

  4. Candida infection of the skin

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000880.htm Candida infection of the skin To use the sharing features ... of the warm, moist conditions inside the diaper. Candida infection is particularly common in people with diabetes and ...

  5. Silicone colonization by non-Candida albicans Candida species in the presence of urine.

    Science.gov (United States)

    Silva, Sónia; Negri, Melyssa; Henriques, Mariana; Oliveira, Rosário; Williams, David; Azeredo, Joana

    2010-07-01

    Urinary tract infections (UTIs) are the most common nosocomial infections and 80 % are related to the use of urinary catheters. Furthermore, Candida species are responsible for around 15 % of UTIs and an increasing involvement of non-Candida albicans Candida (NCAC) species (e.g. Candida glabrata, Candida tropicalis and Candida parapsilosis) has been recognized. Given the fact that silicone is frequently used in the manufacture of urinary catheters, the aim of this work was to compare both the adhesion and biofilm formation on silicone of different urinary clinical isolates of NCAC species (i.e. C. glabrata, C. tropicalis and C. parapsilosis) in the presence of urine. Several clinical isolates of NCAC species recovered from patients with UTIs, together with reference strains of each species, were examined. Adhesion and biofilm formation were performed in artificial urine and the biofilm biomass was assessed by crystal violet staining. Hydrophobicity and surface charge of cells was determined by measuring contact angles and zeta potential, respectively. The number of viable cells in biofilms was determined by enumeration of c.f.u. after appropriate culture. The biofilm structure was also examined by confocal laser scanning microscopy (CLSM). The results showed that all isolates adhered to silicone in a species- and strain-dependent manner with C. parapsilosis showing the lowest and C. glabrata the highest levels of adhesion. However, these differences in adhesion abilities cannot be correlated with surface properties since all strains examined were hydrophilic and exhibited a similar zeta potential. Despite a higher number of cultivable cells being recovered after 72 h of incubation, stronger biofilm formation was not observed and CLSM showed an absence of extracellular polymeric material for all isolates examined. In summary, this work demonstrated that all tested NCAC species were able to adhere to and survive on silicone in the presence of urine. Furthermore, C

  6. 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.

  7. Micafungin triggers caspase-dependent apoptosis in Candida albicans and Candida parapsilosis biofilms, including caspofungin non-susceptible isolates.

    Science.gov (United States)

    Shirazi, F; Kontoyiannis, D P

    2015-01-01

    Candida biofilms play an important role in infections associated with medical devices and are resistant to antifungals. We hypothesized that the echinocandin micafungin (MICA) exerts an enhanced antifungal activity against caspofungin (CAS)-susceptible (CAS-S) and CAS-non-susceptible (CAS-NS) Candida albicans and Candida parapsilosis which is at least in part through apoptosis, even in the biofilm environment. Apoptosis was characterized by detecting reactive oxygen species (ROS) accumulation, depolarization of mitochondrial membrane potential (MMP), DNA fragmentation, lack of plasma membrane integrity, and metacaspase activation following exposure of Candida biofilm to MICA for 3h at 37°C in RPMI 1640 medium. The minimum inhibitory concentration was higher for CAS (2.0-16.0 μg/mL) than for MICA (1.0-8.0 μg/mL) for Candida biofilms. Elevated intracellular ROS levels and depolarization of MMP was evident in CAS-S C. albicans (3.0-4.2 fold) and C. parapsilosis (4.8-5.4 fold) biofilms compared with CAS-NS (1.2 fold) after exposure to MICA (0.25x-1xMIC). Elevated intracellular ROS levels and depolarization of MMP was evident in CAS-S C. albicans (3.0-4.2 fold) and C. parapsilosis (4.8-5.4 fold) biofilms compared with CAS-NS (1.2 fold) after exposure to MICA (0.25x-1xMIC). Finally higher ß-1, 3 glucan levels were seen in sessile cells compared to planktonic cells, especially in CAS-NS strains. MICA treatment might induce a metacaspase-dependent apoptotic process in biofilms of both CAS-S C. albicans and C. parapsilosis, and to some degree in CAS-NS strains.

  8. Effect of Candida albicans on Intestinal Ischemia-reperfusion Injury in Rats

    Institute of Scientific and Technical Information of China (English)

    Lei Yan; Chun-Rong Wu; Chen Wang; Chun-Hui Yang; Guang-Zhi Tong; Jian-Guo Tang

    2016-01-01

    Background:Inflammation is supposed to play a key role in the pathophysiological processes of intestinal ischemia-reperfusion injury (IIRI),and Candida albicans in human gut commonly elevates inflammatory cytokines in intestinal mucosa.This study aimed to explore the effect of C albicans on IIRI.Methods:Fifty female Wistar rats were divided into five groups according to the status of C albicans infection and IIRI operation:group blank and sham;group blank and IIRI;group cefoperazone plus IIRI;group C.albicans plus cefoperazone and IIRI (CCI);and group C.albicans plus cefoperazone and sham.The levels of inflammatory factors tumor necrosis factor (TNF)-α,interleukin (IL)-6,IL-1β,and diamine oxidase (DAO) measured by enzyme-linked immunosorbent assay were used to evaluate the inflammation reactivity as well as the integrity of small intestine.Histological scores were used to assess the mucosal damage,and the C albicans blood translocation was detected to judge the permeability of intestinal mucosal barrier.Results:The levels of inflammatory factors TNF-α,IL-6,and IL-1β in serum and intestine were higher in rats undergone both C.albicans infection and IIRI operation compared with rats in other groups.The levels of DAO (serum:44.13 ± 4.30 pg/ml,intestine:346.21 ± 37.03 pg/g) and Chiu scores (3.41 ± 1.09) which reflected intestinal mucosal disruption were highest in group CCI after the operation.The number of C.albicans translocated into blood was most in group CCI ([33.80 ± 6.60] × 102 colony forming unit (CFU)/ml).Conclusion:Intestinal C.albicans infection worsened the IIRI-induced disruption of intestinal mucosal barrier and facilitated the subsequent C.albicans translocation and dissemination.

  9. The inhibitory activity of linalool against the filamentous growth and biofilm formation in Candida albicans.

    Science.gov (United States)

    Hsu, Chih-Chieh; Lai, Wen-Lin; Chuang, Kuei-Chin; Lee, Meng-Hwan; Tsai, Ying-Chieh

    2013-07-01

    Candida spp. are part of the natural human microbiota, but they also represent important opportunistic human pathogens. Biofilm-associated Candida albicans infections are clinically relevant due to their high levels of resistance to traditional antifungal agents. In this study, we investigated the ability of linalool to inhibit the formation of C. albicans biofilms and reduce existing C. albicans biofilms. Linalool exhibited antifungal activity against C. albicans ATCC 14053, with a minimum inhibitory concentration (MIC) of 8 mM. Sub-MIC concentrations of linalool also inhibited the formation of germ tubes and biofilms in that strain. The defective architecture composition of C. albicans biofilms exposed to linalool was characterized by scanning electron microscopy. The expression levels of the adhesin genes HWP1 and ALS3 were downregulated by linalool, as assessed by real-time RT-PCR. The expression levels of CYR1 and CPH1, which encode components of the cAMP-PKA and MAPK hyphal formation regulatory pathways, respectively, were also suppressed by linalool, as was the gene encoding their upstream regulator, Ras1. The expression levels of long-term hyphae maintenance associated genes, including UME6, HGC1, and EED1, were all suppressed by linalool. These results indicate that linalool may have therapeutic potential in the treatment of candidiasis associated with medical devices because it interferes with the morphological switch and biofilm formation of C. albicans.

  10. Candida Infection of the Bloodstream - Candidemia

    Science.gov (United States)

    Candida Infection of the Bloodstream– Candidemia Fungal Disease Series #4 Candida is the single most important cause of ... Where in my body can I get a Candida infection? Candida infection can happen in almost any part ...

  11. Protective role of antimannan and anti-aspartyl proteinase antibodies in an experimental model of Candida albicans vaginitis in rats.

    OpenAIRE

    De Bernardis, F.; Boccanera, M; Adriani, D; Spreghini, E; G. Santoni; Cassone, A.

    1997-01-01

    The role of antibodies (Abs) in the resistance to vaginal infection by Candida albicans was investigated by using a rat vaginitis model. Animals receiving antimannoprotein (anti-MP) and anti-aspartyl proteinase (Sap) Ab-containing vaginal fluids from rats clearing a primary C. albicans infection showed a highly significant level of protection against vaginitis compared to animals given Ab-free vaginal fluid from noninfected rats. Preabsorption of the Ab-containing fluids with either one or bo...

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Cellular Alterations Induced by Candida albicans RC Nosodes: an in vitro Study

    Directory of Open Access Journals (Sweden)

    Carla Holandino

    2012-09-01

    Full Text Available Introduction: Candidiasis is an opportunist infection, caused by yeast of the genus Candida, which emerges as one of the main causes of systemic infections in hospitalized patients. Candida albicans is the most common causing agent of these infections. According to the Brazilian Homeopathic Pharmacopeia[1], nosodes are medicines compounded from chemically undefined biological products. Living nosodes are prepared using the etiologic agent of an illness in its infective form, were first developed by Brazilian physician Roberto Costa (RC. Roberto Costa’s research indicated that living nosodes present a higher capability to stimulate the host’s immunological system [2]. Aim: This study aims to evaluate cellular alterations induced in C. albicans yeasts and RAW 264-7 macrophages by Candida albicans RC. Methodology: To prepare Candida albicans RC, one part of C. albicans infective yeast suspension (108 cell/ml was diluted in 9 parts of sterile distilled water and submitted to 100 mechanical succussions. This process was successively repeated to the potencies of 12x and 30x1. Water 30x was prepared by the same technique, as control. The cell viability of C. albicans previously treated with nosodes in both potencies and respective controls was evaluated using the samples at the concentration of 10% (V/V, in a volume of 1ml, distributed in 1-3 days. The viability of the yeast cells was analyzed by MTT (3-(4,5-dimetiltiazol-2-il-2,5-difeniltetrazolic (5mg/ml assay [3] and by Propidium Iodide (PI incorporation methods. Additionally, using macrophages RAW 264-7 as a cell model, Nitric Oxide (NO production and cell viability were also evaluated. For this, the following protocol of cell treatment was employed: on each experimental day, RAW 264-7 cells were treated 4 times (4 stimuli with RC nosode 30x at the concentration of 10% (V/V. Results: The nosodes (12x and 30x did not present cytotoxic effects on macrophage

  14. Control of Candida albicans metabolism and biofilm formation by Pseudomonas aeruginosa phenazines.

    Science.gov (United States)

    Morales, Diana K; Grahl, Nora; Okegbe, Chinweike; Dietrich, Lars E P; Jacobs, Nicholas J; Hogan, Deborah A

    2013-01-01

    Candida albicans has developmental programs that govern transitions between yeast and filamentous morphologies and between unattached and biofilm lifestyles. Here, we report that filamentation, intercellular adherence, and biofilm development were inhibited during interactions between Candida albicans and Pseudomonas aeruginosa through the action of P. aeruginosa-produced phenazines. While phenazines are toxic to C. albicans at millimolar concentrations, we found that lower concentrations of any of three different phenazines (pyocyanin, phenazine methosulfate, and phenazine-1-carboxylate) allowed growth but affected the development of C. albicans wrinkled colony biofilms and inhibited the fungal yeast-to-filament transition. Phenazines impaired C. albicans growth on nonfermentable carbon sources and led to increased production of fermentation products (ethanol, glycerol, and acetate) in glucose-containing medium, leading us to propose that phenazines specifically inhibited respiration. Methylene blue, another inhibitor of respiration, also prevented the formation of structured colony biofilms. The inhibition of filamentation and colony wrinkling was not solely due to lowered extracellular pH induced by fermentation. Compared to smooth, unstructured colonies, wrinkled colony biofilms had higher oxygen concentrations within the colony, and wrinkled regions of these colonies had higher levels of respiration. Together, our data suggest that the structure of the fungal biofilm promotes access to oxygen and enhances respiratory metabolism and that the perturbation of respiration by bacterial molecules such as phenazines or compounds with similar activities disrupts these pathways. These findings may suggest new ways to limit fungal biofilms in the context of disease. IMPORTANCE Many of the infections caused by Candida albicans, a major human opportunistic fungal pathogen, involve both morphological transitions and the formation of surface-associated biofilms. Through the

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

    Directory of Open Access Journals (Sweden)

    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

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

    International Nuclear Information System (INIS)

    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 (HBLa+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

  17. Microsatellite-based genotyping of Candida albicans isolated from patients with superficial candidiasis.

    Science.gov (United States)

    Shimizu, Kazue; Hattori, Hisao; Adachi, Hidesada; Oshima, Ryosuke; Horii, Toshinobu; Tanaka, Reiko; Yaguchi, Takashi; Tomita, Yasushi; Akiyama, Masashi; Kawamoto, Fumihiko; Kanbe, Toshio

    2011-01-01

    This study aimed to examine the genotype distribution of Candida albicans and the major genotypes involved in superficial candidiasis. The genotypes of C. albicans isolated from the infection sites of patients with superficial candidiasis (referred to as infection isolates) were analyzed by fragment analysis using 4 microsatellite markers (HIS3, CDC3, CAI and CAIII). Genotypes of the infection isolates were compared with those of C. albicans isolated from oral mucosa of non-candidiasis patients (referred to as oral isolates). Isolates of C. albicans showed 4 major genotypes for HIS3/CAI (" a " for 148 : 148 / 23 : 23," b " for 148 : 160 / 33 : 41," c " for 148 : 164 / 32 : 41 and " d " for 152 : 152 / 18 : 27). The genotypes " a "," b " and " d " were commonly found in oral (4.7, 8.8 and 7.6%, respectively) and infection (6.6, 9.2 and 15.4%, respectively) isolates. No isolates of genotype " c " were isolated from infection sites. The genotype " a " was found in the isolates from patients with genitalia candidiasis. Genotyping of multiple isolates from an individual patient showed that C. albicans from infection sites was genetically homogenous as compared with that of oral isolates, even in the same patient with candidiasis.

  18. Global transcriptome sequencing identifies chlamydospore specific markers in Candida albicans and Candida dubliniensis.

    Directory of Open Access Journals (Sweden)

    Katja Palige

    Full Text Available Candida albicans and Candida dubliniensis are pathogenic fungi that are highly related but differ in virulence and in some phenotypic traits. During in vitro growth on certain nutrient-poor media, C. albicans and C. dubliniensis are the only yeast species which are able to produce chlamydospores, large thick-walled cells of unknown function. Interestingly, only C. dubliniensis forms pseudohyphae with abundant chlamydospores when grown on Staib medium, while C. albicans grows exclusively as a budding yeast. In order to further our understanding of chlamydospore development and assembly, we compared the global transcriptional profile of both species during growth in liquid Staib medium by RNA sequencing. We also included a C. albicans mutant in our study which lacks the morphogenetic transcriptional repressor Nrg1. This strain, which is characterized by its constitutive pseudohyphal growth, specifically produces masses of chlamydospores in Staib medium, similar to C. dubliniensis. This comparative approach identified a set of putatively chlamydospore-related genes. Two of the homologous C. albicans and C. dubliniensis genes (CSP1 and CSP2 which were most strongly upregulated during chlamydospore development were analysed in more detail. By use of the green fluorescent protein as a reporter, the encoded putative cell wall related proteins were found to exclusively localize to C. albicans and C. dubliniensis chlamydospores. Our findings uncover the first chlamydospore specific markers in Candida species and provide novel insights in the complex morphogenetic development of these important fungal pathogens.

  19. Global Transcriptome Sequencing Identifies Chlamydospore Specific Markers in Candida albicans and Candida dubliniensis

    LENUS (Irish Health Repository)

    Palige, Katja

    2013-04-15

    Candida albicans and Candida dubliniensis are pathogenic fungi that are highly related but differ in virulence and in some phenotypic traits. During in vitro growth on certain nutrient-poor media, C. albicans and C. dubliniensis are the only yeast species which are able to produce chlamydospores, large thick-walled cells of unknown function. Interestingly, only C. dubliniensis forms pseudohyphae with abundant chlamydospores when grown on Staib medium, while C. albicans grows exclusively as a budding yeast. In order to further our understanding of chlamydospore development and assembly, we compared the global transcriptional profile of both species during growth in liquid Staib medium by RNA sequencing. We also included a C. albicans mutant in our study which lacks the morphogenetic transcriptional repressor Nrg1. This strain, which is characterized by its constitutive pseudohyphal growth, specifically produces masses of chlamydospores in Staib medium, similar to C. dubliniensis. This comparative approach identified a set of putatively chlamydospore-related genes. Two of the homologous C. albicans and C. dubliniensis genes (CSP1 and CSP2) which were most strongly upregulated during chlamydospore development were analysed in more detail. By use of the green fluorescent protein as a reporter, the encoded putative cell wall related proteins were found to exclusively localize to C. albicans and C. dubliniensis chlamydospores. Our findings uncover the first chlamydospore specific markers in Candida species and provide novel insights in the complex morphogenetic development of these important fungal pathogens.

  20. Characterization of plant-derived saponin natural products against Candida albicans

    OpenAIRE

    Jeffrey J Coleman; Okoli, Ikechukwu; Tegos, George P.; Holson, Edward B.; Wagner, Florence F.; Hamblin, Michael R.; Mylonakis, Eleftherios

    2010-01-01

    Candida albicans is an opportunistic fungal pathogen capable life-threatening disseminated infections particularly in immunocompromised patients. Resistance to many clinically used antifungal agents has created a need to identify and develop a new generation of compounds for therapeutic use. A compound screen to identify potential antifungal natural products was undertaken, identifying 12 saponins, some of which have not been previously described. In the Caenorhabditis elegans model, some sap...

  1. Role of granulocytes in increased host resistance to Candida albicans induced by recombinant interleukin-1.

    OpenAIRE

    Kullberg, B J; Van't Wout, J W; van Furth, R

    1990-01-01

    The effect of human recombinant interleukin-1 alpha (IL-1 alpha) on a systemic candidal infection in mice under various conditions of immunosuppression was investigated. In normal mice and in mice pretreated with cyclophosphamide, hydrocortisone acetate, or sublethal total body irradiation, the outgrowth of Candida albicans in the kidney was significantly reduced by the administration of a single intraperitoneal dose of 80 ng of IL-1 (P less than 0.05). In mice treated with either cyclophosph...

  2. Preparation of Candida albicans Biofilms Using an in vivo Rat Central Venous Catheter Model

    OpenAIRE

    Taff, Heather T; Marchillo, Karen; Andes, David R.

    2013-01-01

    In vivo biofilms grown on medical devices are necessary to understand the interactions of the fungal biofilm and the host environment in which it is most commonly found. This protocol describes a way to grow Candida albicans biofilms on the interior lumen of central venous catheters surgically implanted into rats, which mimics quite well the clinical cases of biofilms found on human central venous catheters. These infected catheters can then be studied via a multitude of different experiments...

  3. Inborn errors of mucocutaneous immunity to Candida albicans in humans: a role for IL-17 cytokines?

    OpenAIRE

    Puel, Anne; Picard, Capucine; Cypowyj, Sophie; Lilic, Desa; Abel, Laurent; Casanova, Jean-Laurent

    2010-01-01

    The various clinical manifestations of chronic mucocutaneous candidiasis (CMC) often result from acquired T-cell immunodeficiencies. More rarely, CMC results from inborn errors of immunity, the recent dissection of which has shed light on the molecular mechanisms of mucocutaneous immunity to Candida albicans. CMC may accompany various other infectious diseases in patients with almost any broad and profound T-cell primary immunodeficiency. By contrast, CMC is one of the few key infections in p...

  4. [Killer toxin and enzyme production by Candida albicans isolated from buccal mucosa in patients with cancer].

    Science.gov (United States)

    de Oliveira, E E; Silva, S C; Soares, A J; Attux, C; Cruvinel, B; Silva, M do R

    1998-01-01

    Opportunistic infections of the oral cavity are primarily caused by Candida and frequently occur in patients with cancer who are undergoing chemotherapy and antibiotic treatment. Of the specimens received from the oral mucosa of 44 patients with cancer, 25 (56.8%) yielded Candida on culture in Sabouraud agar. Twenty four of these isolates were identified as C. albicans (96%) and 1 as C. krusei (4%). The phenotypic characteristics of these isolates showed that all of them were strongly proteolytic, had a high ability to produce phospholipase, and presented the byotypes characterized as 811 (95.8%) and 511 (4.2%) in terms of susceptibility to killer toxins. PMID:9859695

  5. Genotype comparisons of strains of Candida albicans from patients with cutaneous candidiasis and vaginal candidiasis

    Institute of Scientific and Technical Information of China (English)

    SHE Xiao-dong; WANG Xue-jun; FU Mei-hua; SHEN Yong-nian; LIU Wei-da

    2008-01-01

    Background It is uncertain whether genotypes of Candida albicans (C. Albicans) are associated with colonizing body locations or variant conditions of infection. The aim of this study was to investigate whether there are significant associations between strain genotypes and body sites of infection and to determine the potential pathogenesis of cutaneous candidiasis at multiple locations.Methods A total of 151 strains of C. Albicans were isolated from 74 infant patients with cutaneous candidiasis and 61 female patients with vaginal candidiasis. Patients were grouped according to the body sites and underlying conditions of infection. Genolypes were identified by polymerase chain reaction (PCR) of the 25S rDNA and PCR-restriction fragment length polymorphism (RFLP) of ALT repeals digested with EcoRI and Clal.Results Ten genotypes were detected. There were significant differences in genotype frequencies between the two groups. However, we found no clear association between genotypes and the sites of cutaneous infection or the underlying conditions of vaginal candidiasis (VVC). In addition, strains of C. Albicans from multiple cutaneous locations of the same patient had identical genotypes.Conclusions Populations of C. Albicans from patients with cutaneous and vaginal candidiasis were genetically different. However, the lack of genetic difference between strains from different body sites with cutaneous infections or from different underlying conditions for VVC suggests no evidence of genotype selection for different skin surfaces or patients with different underlying conditions for VVC.

  6. Comparative genomics of the fungal pathogens Candida dubliniensis and Candida albicans.

    LENUS (Irish Health Repository)

    Jackson, Andrew P

    2009-12-01

    Candida dubliniensis is the closest known relative of Candida albicans, the most pathogenic yeast species in humans. However, despite both species sharing many phenotypic characteristics, including the ability to form true hyphae, C. dubliniensis is a significantly less virulent and less versatile pathogen. Therefore, to identify C. albicans-specific genes that may be responsible for an increased capacity to cause disease, we have sequenced the C. dubliniensis genome and compared it with the known C. albicans genome sequence. Although the two genome sequences are highly similar and synteny is conserved throughout, 168 species-specific genes are identified, including some encoding known hyphal-specific virulence factors, such as the aspartyl proteinases Sap4 and Sap5 and the proposed invasin Als3. Among the 115 pseudogenes confirmed in C. dubliniensis are orthologs of several filamentous growth regulator (FGR) genes that also have suspected roles in pathogenesis. However, the principal differences in genomic repertoire concern expansion of the TLO gene family of putative transcription factors and the IFA family of putative transmembrane proteins in C. albicans, which represent novel candidate virulence-associated factors. The results suggest that the recent evolutionary histories of C. albicans and C. dubliniensis are quite different. While gene families instrumental in pathogenesis have been elaborated in C. albicans, C. dubliniensis has lost genomic capacity and key pathogenic functions. This could explain why C. albicans is a more potent pathogen in humans than C. dubliniensis.

  7. 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.

  8. Candida albicans exposures, sex specificity and cognitive deficits in schizophrenia and bipolar disorder

    Science.gov (United States)

    Severance, Emily G; Gressitt, Kristin L; Stallings, Catherine R; Katsafanas, Emily; Schweinfurth, Lucy A; Savage, Christina L; Adamos, Maria B; Sweeney, Kevin M; Origoni, Andrea E; Khushalani, Sunil; Leweke, F Markus; Dickerson, Faith B; Yolken, Robert H

    2016-01-01

    Immune aberrations in schizophrenia and bipolar disorder have led to the hypotheses that infectious agents or corresponding immune responses might contribute to psychiatric etiopathogeneses. We investigated case–control differences in exposure to the opportunistic fungal pathogen, Candida albicans, and examined associations with cognition, medication, lifestyle, and somatic conditions. We quantified C. albicans IgG antibodies in two cohorts totaling 947 individuals and evaluated odds ratios (OR) of exposure with psychiatric disorder using multivariate regressions. The case–control cohort included 261 with schizophrenia, 270 with bipolar disorder, and 277 non-psychiatric controls; the second included 139 with first-episode schizophrenia, 78 of whom were antipsychotic naive. No differences in C. albicans exposures were found until diagnostic groups were stratified by sex. In males, C. albicans seropositivity conferred increased odds for a schizophrenia diagnosis (OR 2.04–9.53, P⩽0.0001). In females, C. albicans seropositivity conferred increased odds for lower cognitive scores on Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) in schizophrenia (OR 1.12, P⩽0.004), with significant decreases on memory modules for both disorders (P⩽0.0007–0.03). C. albicans IgG levels were not impacted by antipsychotic medications. Gastrointestinal (GI) disturbances were associated with elevated C. albicans in males with schizophrenia and females with bipolar disorder (P⩽0.009–0.02). C. albicans exposure was associated with homelessness in bipolar males (P⩽0.0015). In conclusion, sex-specific C. albicans immune responses were evident in psychiatric disorder subsets. Inquiry regarding C. albicans infection or symptoms may expedite amelioration of this treatable comorbid condition. Yeast exposure as a risk factor for schizophrenia and its associated cognitive and GI effects require further investigation including the possible contribution of

  9. 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.

  10. Candida albicans exposures, sex specificity and cognitive deficits in schizophrenia and bipolar disorder.

    Science.gov (United States)

    Severance, Emily G; Gressitt, Kristin L; Stallings, Catherine R; Katsafanas, Emily; Schweinfurth, Lucy A; Savage, Christina L; Adamos, Maria B; Sweeney, Kevin M; Origoni, Andrea E; Khushalani, Sunil; Leweke, F Markus; Dickerson, Faith B; Yolken, Robert H

    2016-01-01

    Immune aberrations in schizophrenia and bipolar disorder have led to the hypotheses that infectious agents or corresponding immune responses might contribute to psychiatric etiopathogeneses. We investigated case-control differences in exposure to the opportunistic fungal pathogen, Candida albicans, and examined associations with cognition, medication, lifestyle, and somatic conditions. We quantified C. albicans IgG antibodies in two cohorts totaling 947 individuals and evaluated odds ratios (OR) of exposure with psychiatric disorder using multivariate regressions. The case-control cohort included 261 with schizophrenia, 270 with bipolar disorder, and 277 non-psychiatric controls; the second included 139 with first-episode schizophrenia, 78 of whom were antipsychotic naive. No differences in C. albicans exposures were found until diagnostic groups were stratified by sex. In males, C. albicans seropositivity conferred increased odds for a schizophrenia diagnosis (OR 2.04-9.53, P⩽0.0001). In females, C. albicans seropositivity conferred increased odds for lower cognitive scores on Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) in schizophrenia (OR 1.12, P⩽0.004), with significant decreases on memory modules for both disorders (P⩽0.0007-0.03). C. albicans IgG levels were not impacted by antipsychotic medications. Gastrointestinal (GI) disturbances were associated with elevated C. albicans in males with schizophrenia and females with bipolar disorder (P⩽0.009-0.02). C. albicans exposure was associated with homelessness in bipolar males (P⩽0.0015). In conclusion, sex-specific C. albicans immune responses were evident in psychiatric disorder subsets. Inquiry regarding C. albicans infection or symptoms may expedite amelioration of this treatable comorbid condition. Yeast exposure as a risk factor for schizophrenia and its associated cognitive and GI effects require further investigation including the possible contribution of gut

  11. Antifungal effects of Zataria multiflora and Nigella sativa extracts against Candida albicans

    Directory of Open Access Journals (Sweden)

    Moghim Hassan

    2015-10-01

    Full Text Available Introduction: Candidiasis is a fungal infection caused by Candida albicans. Recentstudies suggest that the side effects of herbal drugs with significant therapeutic effectsare far less than chemical drugs. This study was therefore, conducted to examineantifungal activities of Zataria multif lora and Nigella sativa extracts on C. albicans.Methods: Powders of Z. multif lora and N. sativa were macerated with ethanol 70% and evaporatedat 38˚C by rotary evaporator. The suspension of C. albicans was prepared according to McFarlandat a concentration of approximately 0.5-2.5 × 10CFU/ml. Testing was performed according tomicrobroth dilution in 96-well micro-dilution plates. Minimum inhibitory concentration (MIC,MIC50%, MIC90% and minimum fungicidal concentration (MFC were separately evaluated bycounting the fungal colonies for Z. multif lora and N. sativa.Results: The measured values of MIC, MIC50%, MIC90% and MFC of Z. multiflora on the C.albicans were 0.13, 0.38, 0.74 and 1.03 mg/ml, and those of N. sativa were 10, 27.7, 52.3 and 72.3 mg/ml, respectively.Conclusion: The results indicate that both Zataria multiflora and Nigella sativa extracts are effectiveagainst Candida albicans, but the former species has the highest antifungal activity. If the clinicaltrials confirm the results of this study, Z. multiflora, as a new antifungal agent by replacing chemicaldrugs can be used to develop antifungal medicinal herbs.

  12. 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

  13. Innate Immunity and Saliva in Candida albicans-mediated Oral Diseases.

    Science.gov (United States)

    Salvatori, O; Puri, S; Tati, S; Edgerton, M

    2016-04-01

    The oral cavity is a unique niche where Candida albicans infections occur in immunocompetent as well as immunosuppressed individuals. Here we critically review the significance of human innate immune response in preventing oral candidiasis. One important line of defense against oropharyngeal candidiasis is the oral microbiota that prevents infection by competing for space and nutrients as well as by secreting antagonistic molecules and triggering local inflammatory responses. C. albicans is able to induce mucosal defenses through activation of immune cells and production of cytokines. Also, saliva contains various proteins that affect C. albicans growth positively by promoting mucosal adherence and negatively through immune exclusion and direct fungicidal activity. We further discuss the role of saliva in unifying host innate immune defenses against C. albicans as a communicating medium and how C. albicans overgrowth in the oral cavity may be a result of aberrations ranging from microbial dysbiosis and salivary dysfunction to epithelial damage. Last we underscore select oral diseases in which C. albicans is a contributory microorganism in immune-competent individuals.

  14. O-mannosylation in Candida albicans enables development of interkingdom biofilm communities.

    Science.gov (United States)

    Dutton, Lindsay C; Nobbs, Angela H; Jepson, Katy; Jepson, Mark A; Vickerman, M Margaret; Aqeel Alawfi, Sami; Munro, Carol A; Lamont, Richard J; Jenkinson, Howard F

    2014-04-15

    Candida albicans is a fungus that colonizes oral cavity surfaces, the gut, and the genital tract. Streptococcus gordonii is a ubiquitous oral bacterium that has been shown to form biofilm communities with C. albicans. Formation of dual-species S. gordonii-C. albicans biofilm communities involves interaction of the S. gordonii SspB protein with the Als3 protein on the hyphal filament surface of C. albicans. Mannoproteins comprise a major component of the C. albicans cell wall, and in this study we sought to determine if mannosylation in cell wall biogenesis of C. albicans was necessary for hyphal adhesin functions associated with interkingdom biofilm development. A C. albicans mnt1Δ mnt2Δ mutant, with deleted α-1,2-mannosyltransferase genes and thus defective in O-mannosylation, was abrogated in biofilm formation under various growth conditions and produced hyphal filaments that were not recognized by S. gordonii. Cell wall proteomes of hypha-forming mnt1Δ mnt2Δ mutant cells showed growth medium-dependent alterations, compared to findings for the wild type, in a range of protein components, including Als1, Als3, Rbt1, Scw1, and Sap9. Hyphal filaments formed by mnt1Δ mnt2Δ mutant cells, unlike wild-type hyphae, did not interact with C. albicans Als3 or Hwp1 partner cell wall proteins or with S. gordonii SspB partner adhesin, suggesting defective functionality of adhesins on the mnt1Δ mnt2Δ mutant. These observations imply that early stage O-mannosylation is critical for activation of hyphal adhesin functions required for biofilm formation, recognition by bacteria such as S. gordonii, and microbial community development. IMPORTANCE In the human mouth, microorganisms form communities known as biofilms that adhere to the surfaces present. Candida albicans is a fungus that is often found within these biofilms. We have focused on the mechanisms by which C. albicans becomes incorporated into communities containing bacteria, such as Streptococcus. We find that

  15. Manipulation of Host Diet To Reduce Gastrointestinal Colonization by the Opportunistic Pathogen Candida albicans.

    Science.gov (United States)

    Gunsalus, Kearney T W; Tornberg-Belanger, Stephanie N; Matthan, Nirupa R; Lichtenstein, Alice H; Kumamoto, Carol A

    2016-01-01

    Candida albicans, the most common human fungal pathogen, can cause systemic infections with a mortality rate of ~40%. Infections arise from colonization of the gastrointestinal (GI) tract, where C. albicans is part of the normal microflora. Reducing colonization in at-risk patients using antifungal drugs prevents C. albicans-associated mortalities. C. albicans provides a clinically relevant system for studying the relationship between diet and the microbiota as it relates to commensalism and pathogenicity. As a first step toward a dietary intervention to reduce C. albicans GI colonization, we investigated the impact of dietary lipids on murine colonization by C. albicans. Coconut oil and its constituent fatty acids have antifungal activity in vitro; we hypothesized that dietary coconut oil would reduce GI colonization by C. albicans. Colonization was lower in mice fed a coconut oil-rich diet than in mice fed diets rich in beef tallow or soybean oil. Switching beef tallow-fed mice to a coconut oil diet reduced preexisting colonization. Coconut oil reduced colonization even when the diet also contained beef tallow. Dietary coconut oil also altered the metabolic program of colonizing C. albicans cells. Long-chain fatty acids were less abundant in the cecal contents of coconut oil-fed mice than in the cecal contents of beef tallow-fed mice; the expression of genes involved in fatty acid utilization was lower in C. albicans from coconut oil-fed mice than in C. albicans from beef tallow-fed mice. Extrapolating to humans, these findings suggest that coconut oil could become the first dietary intervention to reduce C. albicans GI colonization. IMPORTANCE Candida albicans, the most common human fungal pathogen, can cause infections with a mortality rate of ~40%. C. albicans is part of the normal gut flora, but when a patient's immune system is compromised, it can leave the gut and cause infections. By reducing the amount of C. albicans in the gut of susceptible

  16. High-Throughput Screening of a Collection of Known Pharmacologically Active Small Compounds for Identification of Candida albicans Biofilm Inhibitors

    OpenAIRE

    Siles, Samuel A.; Srinivasan, Anand; Pierce, Christopher G.; Lopez-Ribot, José L.; Anand K. Ramasubramanian

    2013-01-01

    Candida albicans is the most common etiologic agent of systemic fungal infections with unacceptably high mortality rates. The existing arsenal of antifungal drugs is very limited and is particularly ineffective against C. albicans biofilms. To address the unmet need for novel antifungals, particularly those active against biofilms, we have screened a small molecule library consisting of 1,200 off-patent drugs already approved by the Food and Drug Administration (FDA), the Prestwick Chemical L...

  17. Candida albicans susceptibility to lactoperoxidase-generated hypoiodite

    Directory of Open Access Journals (Sweden)

    Mohamed Ahariz

    2010-08-01

    Full Text Available Mohamed Ahariz1, Philippe Courtois21Laboratory of Experimental Hormonology, Université Libre de Bruxelles, Brussels, Belgium; 2Laboratory of Experimental Hormonology, Université Libre de Bruxelles, Brussels, Belgium and UER de Biologie Médicale, Haute Ecole Francisco Ferrer, Brussels, BelgiumAbstract: In vivo, lactoperoxidase produces hypothiocyanite (OSCN- from thiocyanate (SCN- in the presence of hydrogen peroxide (H2O2; in vitro, iodide (I- can be oxidized into hypoiodite (OI- by this enzyme. The aim of this study was to compare in vitro the anti-Candida effect of iodide versus thiocyanate used as lactoperoxidase substrate to prevent Candida biofilms development. Candida albicans ATCC 10231 susceptibility upon both peroxidase systems was tested in three different experimental designs: (i in a liquid culture medium, (ii in an interface model between solid culture medium and gel containing the enzymic systems, (iii in a biofilm model onto titanium and acrylic resin. Yeast growth in liquid medium was monitored by turbidimetry at 600 nm. Material-adherent yeast biomass was evaluated by the tetrazolium salt MTT method. The iodide-peroxidase system has been shown to inhibit Candida biofilm formation at lower substrate concentrations (~200 fold less H2O2 donor and for longer incubation periods than the thiocyanate-peroxidase system. In conclusion, efficiency of lactoperoxidase-generated OI- to prevent C. albicans biofilm development allows refining iodine antifungal use in ex vivo conditions.Keywords: denture, iodide, oral, peroxidase, saliva, titanium

  18. Sunflower seed husk agar: A new medium for the differentiation of Candida dubliniensis from Candida albicans

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    Khan Z

    2005-01-01

    Full Text Available A sunflower ( Helianthus annuus seed husk agar medium has been developed and evaluated for differentiation of Candida dubliniensis from Candida albicans on the basis of colony morphology and chlamydospore production. All C. dubliniensis isolates (n=40 produced rough colonies with hyphal fringes and abundant chlamydospores whereas 101 of 105 (96.2% C. albicans isolates produced smooth colonies with no evidence of chlamydospore production. Since this medium is free from oil droplets, chlamydospores can be examined with greater clarity by Dalmau plate technique. This medium provides a simple and cost-effective tool for the presumptive differentiation of C. dubliniensis from C. albicans and is particularly suited for clinical microbiology laboratories where biochemical or molecular methods for the differentiation of these two species are not available.

  19. 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.

  20. Application of benzo[a]phenoxazinium chlorides in Antimicrobial Photodynamic Therapy of Candida albicans biofilms.

    Science.gov (United States)

    Lopes, Marisa; Alves, Carlos Tiago; Rama Raju, B; Gonçalves, M Sameiro T; Coutinho, Paulo J G; Henriques, Mariana; Belo, Isabel

    2014-12-01

    The use of Antimicrobial Photodynamic Therapy (APDT) as a new approach to treat localized Candida infections is an emerging and promising field nowadays. The aim of this study was to verify the efficacy of photodynamic therapy using two new benzo[a]phenoxazinium photosensitizers against Candida albicans biofilms: N-(5-(3-hydroxypropylamino)-10-methyl-9H-benzo[a]phenoxazin-9-ylidene)ethanaminium chloride (FSc) and N-(5-(11-hydroxyundecylamino)-10-methyl-9H-benzo[a]phenoxazin-9-ylidene)ethanaminium chloride (FSd). The photodynamic activity of dyes against C. albicans biofilms was evaluated by incubating biofilms with dyes in the range of 100-300 μM for 3 or 18 h followed by illumination at 12 or 36 J cm(-2), using a xenon arc lamp (600 ± 2 nm). A total photoinactivation of C. albicans biofilm cells was achieved using 300 μM of FSc with 18 h of incubation, followed by illumination at 36 J cm(-2). Contrarily, FSd had insignificant effect on biofilms inactivation by APDT. The higher uptake of FSc than FSd dye by biofilms during the dark incubation may explain the greater photodynamic effectiveness achieved with FSc. The results obtained stresses out the FSc-mediated APDT potential use to treat C. albicans infections.

  1. Candida albicans Carriage in Children with Severe Early Childhood Caries (S-ECC) and Maternal Relatedness

    Science.gov (United States)

    Xiao, Jin; Moon, Yonghwi; Li, Lihua; Rustchenko, Elena; Wakabayashi, Hironao; Zhao, Xiaoyi; Feng, Changyong; Gill, Steven R.; McLaren, Sean; Malmstrom, Hans; Ren, Yanfang; Quivey, Robert

    2016-01-01

    Introduction Candida albicans has been detected together with Streptococcus mutans in high numbers in plaque-biofilm from children with early childhood caries (ECC). The goal of this study was to examine the C. albicans carriage in children with severe early childhood caries (S-ECC) and the maternal relatedness. Methods Subjects in this pilot cross-sectional study were recruited based on a convenient sample. DMFT(S)/dmft(s) caries and plaque scores were assessed during a comprehensive oral exam. Social-demographic and related background information was collected through a questionnaire. Saliva and plaque sample from all children and mother subjects were collected. C. albicans were isolated by BBL™ CHROMagar™ and also identified using germ tube test. S. mutans was isolated using Mitis Salivarius with Bacitracin selective medium and identified by colony morphology. Genetic relatedness was examined using restriction endonuclease analysis of the C. albicans genome using BssHII (REAG-B). Multilocus sequence typing was used to examine the clustering information of isolated C. albicans. Spot assay was performed to examine the C. albicans Caspofungin susceptibility between S-ECC children and their mothers. All statistical analyses (power analysis for sample size, Spearman’s correlation coefficient and multiple regression analyses) were implemented with SAS 9.4 Results A total of 18 S-ECC child-mother pairs and 17 caries free child-mother pairs were enrolled in the study. Results indicated high C. albicans carriage rate in the oral cavity (saliva and plaque) of both S-ECC children and their mothers (>80%). Spearman’s correlation coefficient also indicated a significant correlation between salivary and plaque C. albicans and S. mutans carriage (pcaries severity (pcaries-free children). Among 18 child-mother pairs, >60% of them demonstrated identical C. albicans REAG-B pattern. C. albicans isolated from >65% of child-mother pairs demonstrated similar susceptibility to

  2. 肿瘤患者感染白色念珠菌原因分析与对策%Study on the relative risk factors and prevention and countermeasure in malignant tumor patients with Candida albicans infection

    Institute of Scientific and Technical Information of China (English)

    陈少华

    2013-01-01

      目的回顾性分析我院肿瘤患者感染白色念珠菌的发病情况,就其感染的特点及危险因素进行分析研究,探讨防治对策,为合理应用抗菌药物提供参考。方法采用回顾性分析方法,分析2011年6月至2012年6月在我院感染白色念珠菌肿瘤患者68例,对被调查的病历逐一查阅,按年龄、住院天数、感染部位、是否留管及各种侵袭性诊疗操作、免疫抑制剂应用、基础疾病、住院时间长短、是否联合使用抗生素,用药时间及营养状态等作分类登记,并进行总结和分析。结果感染部位分别为口腔20例(29.4%),肺部15例(22.1%),泌尿系8例(11.7%),肠道感染10例(14.7%),真菌血症3例(4.4%),有7例同时存在2个部位感染(10.3%),有5例同时存在3个部位感染(7.3%)。单因素分析结果显示,除年龄(χ2=0.06, P=1.00>0.05,)无统计学意义外,住院时间长短、糖皮质激素的应用、是否联合使用抗生素,用药时间、营养状态、是否留管及各种侵入性诊疗操作等均为感染相关危险因素,有统计学意义(P值均小于0.05)。给予抗真菌治疗后,62例治愈,6例死亡,死亡率8.8%。结论住院时间长短、糖皮质激素的应用、是否联合使用抗生素,用药时间、营养状态、是否留管及各种侵入性诊疗操作等均为肿瘤患者感染白色念珠菌相关危险因素,减少相关危险因素及易感因素是降低肿瘤患者感染白色念珠菌的有效措施。%Objectives To analysis the relative risks factors and formulate the prevention and countermeasure in malignant tumor patients with Candida albicans infection in our hospital. Methods 68 cases of the clinical materials in malignant tumor patients with Candida albicans infection from June 2011 to June 2012 in our hospital were retrospectively analyzed. Results The distribution body parts in malignant tumor patients

  3. Transcriptomics Analysis of Candida albicans Treated with Huanglian Jiedu Decoction Using RNA-seq

    Directory of Open Access Journals (Sweden)

    Qianqian Yang

    2016-01-01

    Full Text Available Candida albicans is the major invasive fungal pathogen of humans, causing diseases ranging from superficial mucosal infections to disseminated, systemic infections that are often life-threatening. Resistance of C. albicans to antifungal agents and limited antifungal agents has potentially serious implications for management of infections. As a famous multiherb prescription in China, Huanglian Jiedu Decoction (HLJJD, Orengedokuto in Japan is efficient against Trichophyton mentagrophytes and C. albicans. But the antifungal mechanism of HLJDD remains unclear. In this study, by using RNA-seq technique, we performed a transcriptomics analysis of gene expression changes for C. albicans under the treatment of HLJDD. A total of 6057 predicted protein-encoding genes were identified. By gene expression analysis, we obtained a total of 735 differentially expressed genes (DEGs, including 700 upregulated genes and 35 downregulated genes. Genes encoding multidrug transporters such as ABC transporter and MFS transporter were identified to be significantly upregulated. Meanwhile, by pathway enrichment analysis, we identified 26 significant pathways, in which pathways of DNA replication and transporter activity were mainly involved. These results might provide insights for the inhibition mechanism of HLJDD against C. albicans.

  4. Function and subcellular localization of Gcn5, a histone acetyltransferase in Candida albicans.

    Science.gov (United States)

    Chang, Peng; Fan, Xueyi; Chen, Jiangye

    2015-08-01

    Candida albicans is an opportunistic fungal pathogen commonly found in humans. It has the ability to switch reversibly between three growth forms: budding yeast, pseudohypha, and hypha. The transition between yeast and hyphal growth forms is critical for the pathogenesis of C. albicans. During the yeast-to-hypha morphologic transition, gene expression is regulated by transcriptional regulators including histone modifying complexes and chromatin remodeling complexes. We previously reported that Esa1, a catalytic subunit in the histone acetyltransferase complex NuA4, is essential for the hyphal development of C. albicans. In this study, we analyzed the functional roles of Gcn5, a catalytic subunit in the histone acetyltransferase complex SAGA, in C. albicans. Gcn5 is required for the invasive and filamentous growth of C. albicans. Deletion of GCN5 impaired hyphal elongation in sensing serum and attenuated the virulence of C. albicans in a mouse systemic infection model. The C. albicans gcn5/gcn5 mutant cells also exhibited sensitivity to cell wall stress. Functional analysis showed that the HAT domain and Bromodomain in Gcn5 play distinct roles in morphogenesis and cell wall stress response of C. albicans. Our results show that the conserved residue Glu188 is crucial for the Gcn5 HAT activity and for Gcn5 function during filamentous growth. In addition, the subcellular distribution of ectopically expressed GFP-Gcn5 correlates with the different growth states of C. albicans. In stationary phase, Gcn5 accumulated in the nucleus, while during vegetative growth it localized in the cytoplasm in a morpha-independent manner. Our results suggest that the nuclear localization of Gcn5 depends on the existence of its N-terminal NLS and HAT domains.

  5. Investigation of ERG11 gene expression among fluconazole-resistant Candida albicans: first report from an Iranian referral paediatric hospital.

    Science.gov (United States)

    Teymuri, M; Mamishi, S; Pourakbari, B; Mahmoudi, S; Ashtiani, M T; Sadeghi, R H; Yadegari, M H

    2015-01-01

    The multiplicity of mechanisms of resistance to azole antifungal agents has been described. As fluconazole-resistant clinical Candida albicans isolates that constitutively over-express ERG11 have been identified in previous studies, the aim of this study is to investigate this molecular mechanism involved in fluconazole resistance of C. albicans clinical isolates. Fluconazole susceptibility testing was carried out on clinical isolates of Candida spp. obtained from hospitalised children in an Iranian referral children's hospital. A polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) technique was used to differentiate Candida spp. The resistant C. albicans isolates were subjected to RT-qPCR using primers that identify ERG11 gene expression. Of the 142 Candida spp. isolates studied, C. albicans was the most predominant isolate, occurring in 68.3% (97/142) of the patients. According to the CLSI method, the majority of the C. albicans isolates (91.7%, 89/97), categorised as susceptible (minimum inhibitory concentration [MIC] ≤8 μg/mL), five isolates were considered resistant (MIC ≤64 μg/mL) and three had dose-dependent susceptibility (MIC = 8.16-32 μg/mL). The ERG11 gene in the five fluconazole-resistant C. albicans isolates was upregulated 4.15-5.84-fold relative to the ATCC 10231 control strain. In this study, the expression of ERG11 was upregulated in all the fluconazole-resistant C. albicans isolates. There are limited data on the antifungal susceptibility of Candida spp. as well as the molecular mechanism of azole resistance in Iran, especially for isolates causing infections in children. Therefore, the surveillance of antifungal resistance patterns and investigation of other mechanisms of azole resistance in all Candida spp. isolates is recommended.

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

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    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

  7. Role of Ess1 in growth, morphogenetic switching, and RNA polymerase II transcription in Candida albicans.

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    Dhanushki Samaranayake

    Full Text Available Candida albicans is a fungal pathogen that causes potentially fatal infections among immune-compromised individuals. The emergence of drug resistant C. albicans strains makes it important to identify new antifungal drug targets. Among potential targets are enzymes known as peptidyl-prolyl cis/trans isomerases (PPIases that catalyze isomerization of peptide bonds preceding proline. We are investigating a PPIase called Ess1, which is conserved in all major human pathogenic fungi. Previously, we reported that C. albicans Ess1 is essential for growth and morphogenetic switching. In the present study, we re-evaluated these findings using more rigorous genetic analyses, including the use of additional CaESS1 mutant alleles, distinct marker genes, and the engineering of suitably-matched isogenic control strains. The results confirm that CaEss1 is essential for growth in C. albicans, but show that reduction of CaESS1 gene dosage by half (δ/+ does not interfere with morphogenetic switching. However, further reduction of CaEss1 levels using a conditional allele does reduce morphogenetic switching. We also examine the role of the linker α-helix that distinguishes C. albicans Ess1 from the human Pin1 enzyme, and present results of a genome-wide transcriptome analysis. The latter analysis indicates that CaEss1 has a conserved role in regulation of RNA polymerase II function, and is required for efficient termination of small nucleolar RNAs and repression of cryptic transcription in C. albicans.

  8. Genetic organization and mRNA expression of enolase genes of Candida albicans.

    Science.gov (United States)

    Postlethwait, P; Sundstrom, P

    1995-04-01

    In previous work, we cloned a Candida albicans cDNA for the glycolytic enzyme enolase and found a single, abundant enolase transcript on Northern (RNA) blots and a single protein on immunoblots, using antiserum raised against a recombinant enolase fusion protein. Because C. albicans enolase is abundantly produced during infection and elicits strong host immune responses, the mechanisms regulating enolase production are important for understanding the growth of C. albicans in vivo. To obtain more information on enolase gene expression by C. albicans, we used the enolase cDNA clone to investigate the genetic organization of enolase genes and the steady-state levels of enolase mRNA under several growth conditions. Gene disruption techniques in combination with Southern blot analyses of genomic DNA showed the presence of two enolase gene loci that could be distinguished by the locations of ClaI and Mn/I sites in their 3' flanking regions. Enolase steady-state mRNA levels were greatest during the middle phase of the logarithmic growth curve and were low during stationary phase. Minimal differences in enolase mRNA levels between yeast cells and hyphae were found. Propagation of C. albicans in glucose did not cause increased enolase mRNA levels compared with growth in a nonfermentable carbon source (pyruvate). It was concluded that two gene loci exist for C. albicans enolase and that enolase mRNA is constitutively produced at high levels during active metabolism. PMID:7896700

  9. Specific induction of fibronectin binding activity by hemoglobin in Candida albicans grown in defined media.

    Science.gov (United States)

    Yan, S; Nègre, E; Cashel, J A; Guo, N; Lyman, C A; Walsh, T J; Roberts, D D

    1996-08-01

    Fibronectin (FN) is a major component of host extracellular matrix that may play an important role in the initiation and dissemination of Candida albicans infections. Expression of FN binding requires growth of C albicans blastoconidia in complex medium, and the regulation of FN receptor expression is poorly understood. We now demonstrate that hemoglobin is a potent and specific inducer of FN receptor expression and describe a defined medium supplemented with hemoglobin that greatly and stably enhances the binding activity of C. albicans for soluble FN. Enhancement of FN binding by hemoglobin in strain 44807 was concentration dependent and was maximal at 0.1% hemoglobin with 20- to 80-fold enhancement. The hemoglobin-induced FN binding to C. albicans was saturable, with a Kd of 2.7 X 10(-8) M. Enhancement required growth of C. albicans in hemoglobin-containing medium, since simply exposing blastoconidia to hemoglobin in a nongrowing status did not enhance binding. Induction was reversible following removal of hemoglobin from the growth medium and not associated with germination. Inorganic or protein-bound iron was not sufficient for the induction, since other iron-containing proteins or inorganic iron salts were inactive. Growth in the simple medium yeast nitrogen base supplemented with hemoglobin increased cell adhesion to immobilized FN and to cultured monolayers of bovine corneal endothelial cells. These data suggest that hemoglobin may be an important regulator of FN binding activity in C. albicans and thus may play a role in its pathogenesis. PMID:8757815

  10. Candida Infections: An Update on Host Immune Defenses and Anti-Fungal Drugs

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    Ning Gao

    2016-04-01

    Full Text Available Infections by fungal pathogens such as Candida albicans and non-albicans Candida species are becoming increasing prevalent in the human population. Such pathogens cause life-threatening diseases with high mortality, particularly in immunocompromised patients. Host defenses against fungal infections are provided by an exquisite interplay between innate and adaptive immune responses. However, effective anti-fungal agents for Candida infections are limited, and fungal drug resistance is a significant treatment challenge. In this review, we summarize the current understanding of host–fungal interactions, discuss the modes action of anti-fungal drugs, explore host defense mechanisms, and define the new challenges for treating Candida infections.

  11. A Human-Curated Annotation of the Candida albicans Genome.

    Directory of Open Access Journals (Sweden)

    2005-07-01

    Full Text Available Recent sequencing and assembly of the genome for the fungal pathogen Candida albicans used simple automated procedures for the identification of putative genes. We have reviewed the entire assembly, both by hand and with additional bioinformatic resources, to accurately map and describe 6,354 genes and to identify 246 genes whose original database entries contained sequencing errors (or possibly mutations that affect their reading frame. Comparison with other fungal genomes permitted the identification of numerous fungus-specific genes that might be targeted for antifungal therapy. We also observed that, compared to other fungi, the protein-coding sequences in the C. albicans genome are especially rich in short sequence repeats. Finally, our improved annotation permitted a detailed analysis of several multigene families, and comparative genomic studies showed that C. albicans has a far greater catabolic range, encoding respiratory Complex 1, several novel oxidoreductases and ketone body degrading enzymes, malonyl-CoA and enoyl-CoA carriers, several novel amino acid degrading enzymes, a variety of secreted catabolic lipases and proteases, and numerous transporters to assimilate the resulting nutrients. The results of these efforts will ensure that the Candida research community has uniform and comprehensive genomic information for medical research as well as for future diagnostic and therapeutic applications.

  12. Candida urinary tract infection and Candida species susceptibilities to antifungal agents.

    Science.gov (United States)

    Osawa, Kayo; Shigemura, Katsumi; Yoshida, Hiroyuki; Fujisawa, Masato; Arakawa, Soichi

    2013-11-01

    The purpose of this study is to review Candida isolation from urine of urinary tract infection (UTI) patients over the recent 3 years at the Kobe University Hospital. We recorded the type of strain, the department where the patient was treated such as the intensive care unit (ICU), and combined isolation of Candida with other microorganisms. We investigated Candida isolation and susceptibilities to antifungal agents and analyzed the risk factors for combined isolation with other microorganisms. The most frequently isolated Candida was Candida albicans, which showed good (100%) susceptibilities to 5-fluorocytosine (5-FC) and fluconazole (FLCZ) but not to voriconazole (VRCZ), followed by C. glabrata. ICU was the greatest source of Candida-positive samples, and the most relevant underlying diseases of ICU patients were pneumonia followed by renal failure and post liver transplantation status. Combined isolation with other bacteria was seen in 27 cases (42.9%) in 2009, 25 (33.3%) in 2010 and 31 (31.3%) in 2011 and comparatively often seen in non-ICU patients. Other candidas than C. albicans showed significantly decreased susceptibility to FLCZ over these 3 years (P=0.004). One hundred (97.1%) of 103 ICU cases were given antibiotics at the time of Candida isolation, and the most often used antibiotics were cefazolin or meropenem. In conclusion, C. albicans was representatively isolated in Candida UTI and showed good susceptibilities to 5-FC, FLCZ and VRCZ, but other candidas than C. albicans showed significantly decreased susceptibility to FLCZ in the change of these 3 years.

  13. The role of micro-organisms (Staphylococcus aureus and Candida albicans in the pathogenesis of breast pain and infection in lactating women: study protocol

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    Tabrizi Sepehr N

    2011-07-01

    Full Text Available Abstract Background The CASTLE (Candida and Staphylococcus Transmission: Longitudinal Evaluation study will investigate the micro-organisms involved in the development of mastitis and "breast thrush" among breastfeeding women. To date, the organism(s associated with the development of breast thrush have not been identified. The CASTLE study will also investigate the impact of physical health problems and breastfeeding problems on maternal psychological health in the early postpartum period. Methods/Design The CASTLE study is a longitudinal descriptive study designed to investigate the role of Staphylococcus spp (species and Candida spp in breast pain and infection among lactating women, and to describe the transmission dynamics of S. aureus and Candida spp between mother and infant. The relationship between breastfeeding and postpartum health problems as well as maternal psychological well-being is also being investigated. A prospective cohort of four hundred nulliparous women who are at least thirty six weeks gestation pregnant are being recruited from two hospitals in Melbourne, Australia (November 2009 to June 2011. At recruitment, nasal, nipple (both breasts and vaginal swabs are taken and participants complete a questionnaire asking about previous known staphylococcal and candidal infections. Following the birth, participants are followed-up six times: in hospital and then at home weekly until four weeks postpartum. Participants complete a questionnaire at each time points to collect information about breastfeeding problems and postpartum health problems. Nasal and nipple swabs and breast milk samples are collected from the mother. Oral and nasal swabs are collected from the baby. A telephone interview is conducted at eight weeks postpartum to collect information about postpartum health problems and breastfeeding problems, such as mastitis and nipple and breast pain. Discussion This study is the first longitudinal study of the role of both

  14. HIV相关性口腔白色念珠菌rDNA基因型研究%rDNA Genotyping of Oral Candida albicans Isolated from HIV-infected Population

    Institute of Scientific and Technical Information of China (English)

    张云操; 刘奇; 武有聪; 郭利军; 申元英; 白丽

    2011-01-01

    Objective: To investigate the distribution of genotypes of oral Candida albicans isolated from HIV-related group and healthy carriers group.Methods: PCR with CA-INT primers was designed to amplify group 1 intron-containing region in 25S rDNA of oral Candida albicans,the different strains of oral Candida albicans were classified into genotypes on the basis of bands from amplicons.Then the genotypic distribution results of all oral Candida albicans were analyzed with SPSS 17.0 by chi-square test.Results: One hundred and eight strains of oral cavities Candida albicans were classified into genotype A,B and C.Genotype A was the most predominant one.Identical genotypes distribution appeared in both groups.But the constituent ratio of genotype A of oral Candida albicans strains in HIV-positive group was statistically higher compared to the healthy people group.Conclusion: Genotypes of oral Candida albicans in both groups were highly polymorphic.The method in text is suitable to apply in genotyping research of oral Candida albicans.%目的:了解HIV感染人群和健康人群口腔白色念珠菌基因型的分布情况。方法:运用CA-INT特异性引物聚合酶链反应方法扩增白色念珠菌包含1类内含子的编码rRNA的25S rDNA区,根据扩增条带大小进行基因分型,并应用χ2检验对54株HIV感染人群和54株健康人群口腔白色念珠菌基因型别进行分析。结果:CA-INT特异性引物PCR法可将108株口腔白色念珠菌分为A、B和C型,以A型最多见,两组人群口腔白色念珠菌基因型分布基本相同,但HIV感染人群口腔白色念珠菌A型所占构成比高于健康人群,差别有统计学意义。结论:HIV感染人群和健康人群口腔白色念珠菌均具有基因多态性,CA-INT特异性引物PCR法是较好的口腔白色念珠菌种内菌株间鉴定的方法。

  15. Streptococcus gordonii glucosyltransferase promotes biofilm interactions with Candida albicans

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    Austin Ricker

    2014-01-01

    Full Text Available Background: Candida albicans co-aggregates with Streptococcus gordonii to form biofilms and their interactions in mucosal biofilms may lead to pathogenic synergy. Although the functions of glucosyltransferases (Gtf of Mutans streptococci have been well characterized, the biological roles of these enzymes in commensal oral streptococci, such as S. gordonii, in oral biofilm communities are less clear. Objective: The objective of this work was to explore the role of GtfG, the single Gtf enzyme of S. gordonii, in biofilm interactions with C. albicans. Design: Biofilms were grown under salivary flow in flow cells in vitro, or under static conditions in 96 well plates. A panel of isogenic S. gordonii CH1 gtfG mutants and complemented strains were co-inoculated with C. albicans strain SC5314 to form mixed biofilms. Biofilm accretion and binding interactions between the two organisms were tested. Biofilms were quantified using confocal microscopy or the crystal violet assay. Results: The presence of GtfG enhanced dual biofilm accretion, and sucrose supplementation further augmented dual biofilm formation, pointing to a role of newly synthesized glucans. GtfG also promoted binding to C. albicans preformed biofilms. Soluble α-1,6-glucans played a role in these interactions since: 1 a strain producing only soluble glucans (CH107 formed robust dual biofilms under conditions of salivary flow; and 2 the dual biofilm was susceptible to enzymatic breakdown by dextranase which specifically degrades soluble α-1,6-glucans. Conclusion: Our work identified a novel molecular mechanism for C. albicans and S. gordonii biofilm interactions, mediated by GtfG. This protein promotes early biofilm binding of S. gordonii to C. albicans which leads to increased accretion of streptococcal cells in mixed biofilms. We also showed that soluble glucans, with α-1,6-linkages, promoted inter-generic adhesive interactions.

  16. Candida species biofilm and Candida albicans ALS3 polymorphisms in clinical isolates

    OpenAIRE

    Ariane Bruder-Nascimento; Carlos Henrique Camargo; Alessandro Lia Mondelli; Maria Fátima Sugizaki; Terue Sadatsune; Eduardo Bagagli

    2015-01-01

    Over the last decades, there have been important changes in the epidemiology of Candida infections. In recent years, Candida species have emerged as important causes of invasive infections mainly among immunocompromised patients. This study analyzed Candida spp. isolates and compared the frequency and biofilm production of different species among the different sources of isolation: blood, urine, vulvovaginal secretions and peritoneal dialysis fluid. Biofilm production was quantified in 327 Ca...

  17. Clusters of patients with candidaemia due to genotypes of Candida albicans and Candida parapsilosis: differences in frequency between hospitals.

    Science.gov (United States)

    Marcos-Zambrano, L J; Escribano, P; Sanguinetti, M; Gómez G de la Pedrosa, E; De Carolis, E; Vella, A; Cantón, R; Bouza, E; Guinea, J

    2015-07-01

    The presence of clusters (identical genotypes infecting different patients) suggests patient-to-patient transmission or a common source for strains. We report the results of a genotyping study based on microsatellite markers of Candida albicans (n = 179) and Candida parapsilosis (n = 76) causing candidaemia, to assess and compare the percentage of patients grouped in clusters during the study period (January 2010 to December 2012). The study was performed in two large tertiary hospitals in Madrid, Spain. We detected 145 C. albicans genotypes (21 in clusters) and 63 C. parapsilosis genotypes (seven in clusters). Clusters involved two to seven patients each. Most of the clusters in the two centres involved two patients for both species, but the number of patients included in each cluster differed between hospitals. Considering both species, the percentage of patients per cluster ranged from 19% to 38% (p albicans and C. parapsilosis genotypes causing candidaemia differed between hospitals, suggesting differences in strain transmission. Occasionally, the same genotypes were found in patients admitted to different hospitals located in the same city.

  18. Antifungal activity of clotrimazole against Candida albicans depends on carbon sources, growth phase and morphology.

    Science.gov (United States)

    Kasper, Lydia; Miramón, Pedro; Jablonowski, Nadja; Wisgott, Stephanie; Wilson, Duncan; Brunke, Sascha; Hube, Bernhard

    2015-07-01

    Vulvovaginal candidiasis, a superficial infection caused predominantly by the pathogenic fungus Candida albicans, is frequently treated with clotrimazole. Some drug formulations contain lactate for improved solubility. Lactate may modify C. albicans physiology and drug sensitivity by serving as a carbon source for the fungus and/or affecting local pH. Here, we explored the effects of lactate, in combination with pH changes, on C. albicans proliferation, morphology and clotrimazole sensitivity. Moreover, we determined the influence of growth phase and morphology per se on drug sensitivity. We showed that utilization of lactate as a carbon source did not promote fast fungal proliferation or filamentation. Lactate had no influence on clotrimazole-mediated killing of C. albicans in standard fungal cultivation medium but had an additive effect on the fungicidal clotrimazole action under in vitro vagina-simulative conditions. Moreover, clotrimazole-mediated killing was growth-phase and morphology dependent. Post-exponential cells were resistant to the fungicidal action of clotrimazole, whilst logarithmic cells were sensitive, and hyphae showed the highest susceptibility. Finally, we showed that treatment of pre-formed C. albicans hyphae with sublethal concentrations of clotrimazole induced a reversion to yeast-phase growth. As C. albicans hyphae are considered the pathogenic morphology during mucosal infections, these data suggest that elevated fungicidal activity of clotrimazole against hyphae plus clotrimazole-induced hyphae-to-yeast reversion may help to dampen acute vaginal infections by reducing the relative proportion of hyphae and thus shifting to a non-invasive commensal-like population. In addition, lactate as an ingredient of clotrimazole formulations may potentiate clotrimazole killing of C. albicans in the vaginal microenvironment. PMID:25976001

  19. The GRF10 homeobox gene regulates filamentous growth in the human fungal pathogen Candida albicans.

    Science.gov (United States)

    Ghosh, Anup K; Wangsanut, Tanaporn; Fonzi, William A; Rolfes, Ronda J

    2015-12-01

    Candida albicans is the most common human fungal pathogen and can cause life-threatening infections. Filamentous growth is critical in the pathogenicity of C. albicans, as the transition from yeast to hyphal forms is linked to virulence and is also a pivotal process in fungal biofilm development. Homeodomain-containing transcription factors have been linked to developmental processes in fungi and other eukaryotes. We report here on GRF10, a homeobox transcription factor-encoding gene that plays a role in C. albicans filamentation. Deletion of the GRF10 gene, in both C. albicans SN152 and BWP17 strain backgrounds, results in mutants with strongly decreased hyphal growth. The mutants are defective in chlamydospore and biofilm formation, as well as showing dramatically attenuated virulence in a mouse infection model. Expression of the GRF10 gene is highly induced during stationary phase and filamentation. In summary, our study emphasizes a new role for the homeodomain-containing transcription factor in morphogenesis and pathogenicity of C. albicans.

  20. Application of surface plasmon resonance biosensor for the detection of Candida albicans

    Science.gov (United States)

    Yodmongkol, Sirasa; Thaweboon, Sroisiri; Thaweboon, Boonyanit; Puttharugsa, Chokchai; Sutapun, Boonsong; Amarit, Ratthasart; Somboonkaew, Armote; Srikhirin, Toemsak

    2016-02-01

    In this study, surface plasmon resonance imaging (SPR imaging) was developed for the detection of Candida albicans which is a causal agent of oral infection. The detection was based on the sandwich assay. The capture antibody was covalently immobilized on the mixed self assemble monolayers (SAMs). The ratio of mixed SAMs between 11-mercaptoundecanoic acid and 3-mercaptopropanol was varied to find the optimal ratio for use as a sensor surface. The results showed that the suitable surface for C. albicans detection was SAM of carboxylic (mixed SAMs 1:0), even though mixed SAMs 1:40 had a high detection signal in comparison to mixed SAMs 1:0, but the non-specific signal was higher. The detection limit was 107 cells/ml for direct detection, and was increased to 106 cells/ml with sandwich antibody. The use of polyclonal C. albicans antibody as capture and sandwich antibody showed good selectivity against the relevant oral bacteria including Escherichia coli, Streptococcus mutan, Staphylococcus aureus, β-streptococci, and Lactobacillus casei. SPR platform in this study could detect C. albicans from the mixed microbial suspension without requirement of skillful technician. This SPR imaging biosensor could be applied for Candida identification after cultivation.

  1. Initiation of phospholipomannan β-1,2 mannosylation involves Bmts with redundant activity, influences its cell wall location and regulates β-glucans homeostasis but is dispensable for Candida albicans systemic infection.

    Science.gov (United States)

    Courjol, F; Mille, C; Hall, R A; Masset, A; Aijjou, R; Gow, N A R; Poulain, D; Jouault, T; Fradin, C

    2016-01-01

    Pathogenic and non-pathogenic fungi synthesize glycosphingolipids, which have a crucial role in growth and viability. Glycosphingolipids also contribute to fungal-associated pathogenesis. The opportunistic yeast pathogen Candida albicans synthesizes phospholipomannan (PLM), which is a glycosphingolipid of the mannosylinositol phosphorylceramide family. Through its lipid and glycan moieties, PLM contributes to the initial recognition of the yeast, causing immune system disorder and persistent fungal disease through activation of host signaling pathways. The lipid moiety of PLM activates the deregulation signaling pathway involved in yeast phagocytosis whereas its glycan moiety, composed of β-1,2 mannosides (β-Mans), participates to inflammatory processes through a mechanism involving Galectin-3. Biosynthesis of PLM β-Mans involves two β-1,2 mannosyltransferases (Bmts) that initiate (Bmt5) and elongate (Bmt6) the glycan chains. After generation of double bmtsΔ mutants, we show that Bmt5 has redundant activity with Bmt2, which can replace Bmt5 in bmt5Δ mutant. We also report that PLM is located in the inner layer of the yeast cell wall. PLM seems to be not essential for systemic infection of the yeast. However, defect of PLM β-mannosylation increases resistance of C. albicans to inhibitors of β-glucans and chitin synthesis, highlighting a role of PLM in cell wall homeostasis.

  2. Effects of ambroxol on Candida albicans growth and biofilm formation.

    Science.gov (United States)

    Rene, Hernandez-Delgadillo; José, Martínez-Sanmiguel Juan; Isela, Sánchez-Nájera Rosa; Claudio, Cabral-Romero

    2014-04-01

    Typically, the onset of candidiasis is characterised by the appearance of a biofilm of Candida albicans, which is associated with several diseases including oral candidiasis in young and elderly people. The objective of this work was to investigate the in vitro fungicidal activity as well as the antibiofilm activity of ambroxol (AMB) against C. albicans growth. In the present investigation, the fungicidal activity of AMB was established using the cell viability 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Also the minimum inhibitory concentration (MIC) of AMB required to inhibit the fungal growth was determined. Simultaneously, the antibiofilm activity of AMB was evaluated using fluorescence microscopy. The study revealed that 2 mg ml(-1) of AMB exhibited higher fungicidal activity than 3.3 mg ml(-1) of terbinafine, one of most common commercial antifungals. A MIC of 1 mg ml(-1) was determined for AMB to interfere with C. albicans growth. Furthermore, AMB was found to be effective in inhibiting the biofilm formation of C. albicans and exerted its fungicidal activity against the fungal cells interspersed in the preformed biofilm. The study suggests a potential role of the mucolytic agent, AMB, as an interesting therapeutic alternative in the treatment of oral candidiasis.

  3. Histone deacetylase-mediated morphological transition in Candida albicans.

    Science.gov (United States)

    Kim, Jueun; Lee, Ji-Eun; Lee, Jung-Shin

    2015-12-01

    Candida albicans is the most common opportunistic fungal pathogen, which switches its morphology from single-cell yeast to filament through the various signaling pathways responding to diverse environmental cues. Various transcriptional factors such as Nrg1, Efg1, Brg1, Ssn6, and Tup1 are the key components of these signaling pathways. Since C. albicans can regulate its transcriptional gene expressions using common eukaryotic regulatory systems, its morphological transition by these signaling pathways could be linked to the epigenetic regulation by chromatin structure modifiers. Histone proteins, which are critical components of eukaryotic chromatin structure, can regulate the eukaryotic chromatin structure through their own modifications such as acetylation, methylation, phosphorylation and ubiquitylation. Recent studies revealed that various histone modifications, especially histone acetylation and deacetylation, participate in morphological transition of C. albicans collaborating with well-known transcription factors in the signaling pathways. Here, we review recent studies about chromatin-mediated morphological transition of C. albicans focusing on the interaction between transcription factors in the signaling pathways and histone deacetylases.

  4. Effects of ambroxol on Candida albicans growth and biofilm formation.

    Science.gov (United States)

    Rene, Hernandez-Delgadillo; José, Martínez-Sanmiguel Juan; Isela, Sánchez-Nájera Rosa; Claudio, Cabral-Romero

    2014-04-01

    Typically, the onset of candidiasis is characterised by the appearance of a biofilm of Candida albicans, which is associated with several diseases including oral candidiasis in young and elderly people. The objective of this work was to investigate the in vitro fungicidal activity as well as the antibiofilm activity of ambroxol (AMB) against C. albicans growth. In the present investigation, the fungicidal activity of AMB was established using the cell viability 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Also the minimum inhibitory concentration (MIC) of AMB required to inhibit the fungal growth was determined. Simultaneously, the antibiofilm activity of AMB was evaluated using fluorescence microscopy. The study revealed that 2 mg ml(-1) of AMB exhibited higher fungicidal activity than 3.3 mg ml(-1) of terbinafine, one of most common commercial antifungals. A MIC of 1 mg ml(-1) was determined for AMB to interfere with C. albicans growth. Furthermore, AMB was found to be effective in inhibiting the biofilm formation of C. albicans and exerted its fungicidal activity against the fungal cells interspersed in the preformed biofilm. The study suggests a potential role of the mucolytic agent, AMB, as an interesting therapeutic alternative in the treatment of oral candidiasis. PMID:24224742

  5. Increased Filamentous Growth of Candida albicans in Simulated Microgravity

    Institute of Scientific and Technical Information of China (English)

    Sara D. Altenburg; Sheila M. Nielsen-Preiss; Linda E. Hyman

    2008-01-01

    Knowledge of simulated microgravity (SMG)-induced changes in the pathogenicity of microorganisms is important for success of long-term spaceflight. In a previous study using the high aspect ratio vessel bioreactor, we showed that the yeast species Saccharomyces cerevisiae underwent a significant phenotypic response when grown in modeled microgravity, which was reflected in the analysis of gene expression profiles. In this study, we establish that Candida albicans responds to SMG in a similar fashion, demonstrating that there is a conserved response among yeast to this environmental stress. We also report that the growth of C. albicans in SMG results in a morphogenic switch that is consistent with enhanced pathogenicity. Specifically, we observed an increase in filamentous forms of the organism and accompanying changes in the expression of two genes associated with the yeasthyphal transition. The morphological response may have significant implications for astronauts' safety, as the fungal pathogen may become more virulent during spaceflight.

  6. 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. PMID:21924704

  7. Pengaruh Perendaman Basis Gigitiruan Resin Akrilik Polimerisasi Panas Dalam Ekstrak Kayu Manis Terhadap Jumlah Candida albicans

    OpenAIRE

    Siahaan, Grace Asima

    2015-01-01

    Resin akrilik polimerisasi panas merupakan bahan yang sering digunakan dalam proses pembuatan basis gigitiruan. Bahan ini memilik sifat kemis dan biologis yang berhubungan dengan pembentukan koloni Candida albicans .Terbentuknya koloni Candida albicans pada basis gigitiruan akan mengakibatkan terjadinya denture stomatitis pada pasien pemakai gigitiruan. Oleh karena itu, dokter gigi memiliki tanggung jawab memberikan instruksi kepada pasien agar menjaga kebersihan gigitiruan dan kebersihan ron...

  8. 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.

  9. Genetic susceptibility to Candida infections

    NARCIS (Netherlands)

    Smeekens, S.P.; Veerdonk, F.L. van de; Kullberg, B.J.; Netea, M.G.

    2013-01-01

    Candida spp. are medically important fungi causing severe mucosal and life-threatening invasive infections, especially in immunocompromised hosts. However, not all individuals at risk develop Candida infections, and it is believed that genetic variation plays an important role in host susceptibility

  10. Impaired killing of Candida albicans by granulocytes mobilized for transfusion purposes: a role for granule components.

    Science.gov (United States)

    Gazendam, Roel P; van de Geer, Annemarie; van Hamme, John L; Tool, Anton T J; van Rees, Dieke J; Aarts, Cathelijn E M; van den Biggelaar, Maartje; van Alphen, Floris; Verkuijlen, Paul; Meijer, Alexander B; Janssen, Hans; Roos, Dirk; van den Berg, Timo K; Kuijpers, Taco W

    2016-05-01

    Granulocyte transfusions are used to treat neutropenic patients with life-threatening bacterial or fungal infections that do not respond to anti-microbial drugs. Donor neutrophils that have been mobilized with granulocyte-colony stimulating factor (G-CSF) and dexamethasone are functional in terms of antibacterial activity, but less is known about their fungal killing capacity. We investigated the neutrophil-mediated cytotoxic response against C. albicans and A. fumigatus in detail. Whereas G-CSF/dexamethasone-mobilized neutrophils appeared less mature as compared to neutrophils from untreated controls, these cells exhibited normal ROS production by the NADPH oxidase system and an unaltered granule mobilization capacity upon stimulation. G-CSF/dexamethasone-mobilized neutrophils efficiently inhibited A. fumigatus germination and killed Aspergillus and Candida hyphae, but the killing of C. albicans yeasts was distinctly impaired. Following normal Candida phagocytosis, analysis by mass spectrometry of purified phagosomes after fusion with granules demonstrated that major constituents of the antimicrobial granule components, including major basic protein (MBP), were reduced. Purified MBP showed candidacidal activity, and neutrophil-like Crisp-Cas9 NB4-KO-MBP differentiated into phagocytes were impaired in Candida killing. Together, these findings indicate that G-CSF/dexamethasone-mobilized neutrophils for transfusion purposes have a selectively impaired capacity to kill Candida yeasts, as a consequence of an altered neutrophil granular content. PMID:26802050

  11. 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.

  12. Probiotic lactobacilli inhibit early stages of Candida albicans biofilm development by reducing their growth, cell adhesion, and filamentation.

    Science.gov (United States)

    Matsubara, Victor Haruo; Wang, Yi; Bandara, H M H N; Mayer, Marcia Pinto Alves; Samaranayake, Lakshman P

    2016-07-01

    We evaluated the inhibitory effects of the probiotic Lactobacillus species on different phases of Candida albicans biofilm development. Quantification of biofilm growth and ultrastructural analyses were performed on C. albicans biofilms treated with Lactobacillus rhamnosus, Lactobacillus casei, and Lactobacillus acidophilus planktonic cell suspensions as well as their supernatants. Planktonic lactobacilli induced a significant reduction (p  0.05), but significantly reduced the early stages of Candida biofilm formation (p < 0.01). Microscopic analyses revealed that L. rhamnosus suspensions reduced Candida hyphal differentiation, leading to a predominance of budding growth. All lactobacilli negatively impacted C. albicans yeast-to-hyphae differentiation and biofilm formation. The inhibitory effects of the probiotic Lactobacillus on C. albicans entailed both cell-cell interactions and secretion of exometabolites that may impact on pathogenic attributes associated with C. albicans colonization on host surfaces and yeast filamentation. This study clarifies, for the first time, the mechanics of how Lactobacillus species may antagonize C. albicans host colonization. Our data elucidate the inhibitory mechanisms that define the probiotic candicidal activity of lactobacilli, thus supporting their utility as an adjunctive therapeutic mode against mucosal candidal infections. PMID:27087525

  13. Control of Candida albicans Metabolism and Biofilm Formation by Pseudomonas aeruginosa Phenazines

    OpenAIRE

    Morales, Diana K.; Grahl, Nora; Okegbe, Chinweike; Dietrich, Lars E. P.; Jacobs, Nicholas J.; Hogan, Deborah A.

    2013-01-01

    ABSTRACT Candida albicans has developmental programs that govern transitions between yeast and filamentous morphologies and between unattached and biofilm lifestyles. Here, we report that filamentation, intercellular adherence, and biofilm development were inhibited during interactions between Candida albicans and Pseudomonas aeruginosa through the action of P. aeruginosa-produced phenazines. While phenazines are toxic to C. albicans at millimolar concentrations, we found that lower concentra...

  14. Effects of salivary protein flow and indigenous microorganisms on initial colonization of Candida albicans in an in vivo model

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    Kanaguchi Norihiko

    2012-08-01

    Full Text Available Abstract Background Candida albicans is a dimorphic fungus that is part of the commensal microbial flora of the oral cavity. When the host immune defenses are impaired or when the normal microbial flora is disturbed, C. albicans triggers recurrent infections of the oral mucosa and tongue. Recently, we produced NOD/SCID.e2f1-/- mice that show hyposalivation, decrease of salivary protein flow, lack IgA and IgG in saliva, and have decreased NK cells. Our objective was to characterize C. albicans infection and biofilm formation in mice. Methods NOD/SCID.e2f1-/- mice were used as an animal model for C. albicans infection. C. albicans yeast and hyphal forms solutions were introduced in the oral cavity after disinfection by Chlorhexidine. Results The numbers of C. albicans colonized and decreased in a time-dependent manner in NOD/SCID.e2f1+/+ after inoculation. However, the colonization levels were higher in NOD/SCID.e2f1+/+ than NOD/SCID.e2f1-/- mice. In the mice fed 1% sucrose water before inoculation, C. albicans sample was highly contaminated by indigenous microorganisms in the oral cavity; and was not in the mice fed no sucrose water. The colonization of C. albicans was not influenced by the contamination of indigenous microorganisms. The hyphal form of C. albicans restricted the restoration of indigenous microorganisms. The decreased saliva in NOD/SCID.e2f1-/- did not increase the colonization of C. albicans in comparison to NOD/SCID.e2f1+/+ mice. We suggest that the receptor in saliva to C. albicans may not be sufficiently provided in the oral cavity of NOD/SCID.e2f1-/- mice. Conclusion The saliva protein flow may be very important for C. albicans initial colonization, where the indigenous microorganisms do not affect colonization in the oral cavity.

  15. Sensitization of Candida albicans biofilms to various antifungal drugs by cyclosporine A

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    Shinde Ravikumar B

    2012-10-01

    Full Text Available Abstract Background Biofilms formed by Candida albicans are resistant towards most of the available antifungal drugs. Therefore, infections associated with Candida biofilms are considered as a threat to immunocompromised patients. Combinatorial drug therapy may be a good strategy to combat C. albicans biofilms. Methods Combinations of five antifungal drugs- fluconazole (FLC, voriconazole (VOR, caspofungin (CSP, amphotericin B (AmB and nystatin (NYT with cyclosporine A (CSA were tested in vitro against planktonic and biofilm growth of C. albicans. Standard broth micro dilution method was used to study planktonic growth, while biofilms were studied in an in vitro biofilm model. A chequerboard format was used to determine fractional inhibitory concentration indices (FICI of combination effects. Biofilm growth was analyzed using XTT-metabolic assay. Results MICs of various antifungal drugs for planktonic growth of C. albicans were lowered in combination with CSA by 2 to 16 fold. Activity against biofilm development with FIC indices of 0.26, 0.28, 0.31 and 0.25 indicated synergistic interactions between FLC-CSA, VOR-CSA, CSP-CSA and AmB-CSA, respectively. Increase in efficacy of the drugs FLC, VOR and CSP against mature biofilms after addition of 62.5 μg/ml of CSA was evident with FIC indices 0.06, 0.14 and 0.37, respectively. Conclusions The combinations with CSA resulted in increased susceptibility of biofilms to antifungal drugs. Combination of antifungal drugs with CSA would be an effective prophylactic and therapeutic strategy against biofilm associated C. albicans infections.

  16. 光动力疗法治疗食管癌合并白色念珠菌感染%Photodynamic Therapy for Esophageal Squamous Cell Carcinoma Associated with Candida albicans Infection

    Institute of Scientific and Technical Information of China (English)

    毛永平; 邱海霞; 顾瑛; 王颖; 朱建国; 曾晶; 刘庆森; 杨云生

    2011-01-01

    目的 观察光动力疗法抗食管真菌感染的疗效.方法 临床及病理确诊为食管癌合并食管白色念珠菌感染的患者1例,静脉注射光敏剂PSD-007 5 mg/kg后6h,以波长630nm的半导体激光(激光功率密度150 mW/cm2)出光段为3 cm的柱状光纤分节段及分次进行照射.食管癌或食管癌合并白色念珠菌感染灶处,每光斑照射30 min;单纯白色念珠菌感染灶,每光斑照射15min.观察术中和术后不良反应发生情况,根据相应标准进行近期临床疗效评价.结果 该患者共进行了3次PDT治疗,其中距门齿21 ~24 cm的食管癌2次治疗后达到完全效应,伴发的白色念珠菌感染1次治疗后治愈;距门齿25 ~28 cm念珠菌性食管炎2次治疗后治愈;距门齿35~33、33~30 cm的食管癌分别经2次和3次治疗后达到明显效应.除距门齿21 ~ 24 cm的食管癌第2次PDT治疗病变完全消失后遗留少量瘢痕外,余区未发生瘢痕,狭窄、穿孔等不良反应.结论 光动力疗法不仅能有效控制进展期食管癌,还能有效治疗食管白色念珠菌感染,具有高选择性、安全、毒副作用小、可重复应用等优点,对食管真菌感染,尤是对食管真菌感染合并食管癌的患者是一种有希望的治疗方法.%Objective To observe the ability of photodynamic therapy to deal with Candida esophagitis.Methods One patient with esophageal squamous cell carcinoma associated with Candida albicans infection confirmed by endoscopy and histopathology was included in the study. PSD-007 at 5 mg/kg body mass was intravenously injected 6 h prior to laser irradiation. A semiconductor laser emitting at 630 run was used as light source. The power density of 150 mW/cm2 was used. To lesions of esophageal squamous cell carcinoma associated with C. Albicans infection or esophageal squamous cell carcinoma alone, the exposure time of30 min and a total light dose of 270 J/cm2 was used at one light spot. To lesion with Candida

  17. Human antimicrobial peptide LL-37 inhibits adhesion of Candida albicans by interacting with yeast cell-wall carbohydrates.

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    Pei-Wen Tsai

    Full Text Available Candida albicans is the major fungal pathogen of humans. Fungal adhesion to host cells is the first step of mucosal infiltration. Antimicrobial peptides play important roles in the initial mucosal defense against C. albicans infection. LL-37 is the only member of the human cathelicidin family of antimicrobial peptides and is commonly expressed in various tissues and cells, including epithelial cells of both the oral cavity and urogenital tract. We found that, at sufficiently low concentrations that do not kill the fungus, LL-37 was still able to reduce C. albicans infectivity by inhibiting C. albicans adhesion to plastic surfaces, oral epidermoid OECM-1 cells, and urinary bladders of female BALB/c mice. Moreover, LL-37-treated C. albicans floating cells that did not adhere to the underlying substratum aggregated as a consequence of LL-37 bound to the cell surfaces. According to the results of a competition assay, the inhibitory effects of LL-37 on cell adhesion and aggregation were mediated by its preferential binding to mannan, the main component of the C. albicans cell wall, and partially by its ability to bind chitin or glucan, which underlie the mannan layer. Therefore, targeting of cell-wall carbohydrates by LL-37 provides a new strategy to prevent C. albicans infection, and LL-37 is a useful, new tool to screen for other C. albicans components involved in adhesion.

  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. 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. PMID:26902505

  20. Two independent killing mechanisms of Candida albicans by human neutrophils: evidence from innate immunity defects.

    Science.gov (United States)

    Gazendam, Roel P; van Hamme, John L; Tool, Anton T J; van Houdt, Michel; Verkuijlen, Paul J J H; Herbst, Martin; Liese, Johannes G; van de Veerdonk, Frank L; Roos, Dirk; van den Berg, Timo K; Kuijpers, Taco W

    2014-07-24

    Invasive fungal infections, accompanied by high rates of mortality, represent an increasing problem in medicine. Neutrophils are the major effector immune cells in fungal killing. Based on studies with neutrophils from patients with defined genetic defects, we provide evidence that human neutrophils use 2 distinct and independent phagolysosomal mechanisms to kill Candida albicans. The first mechanism for the killing of unopsonized C albicans was found to be dependent on complement receptor 3 (CR3) and the signaling proteins phosphatidylinositol-3-kinase and caspase recruitment domain-containing protein 9 (CARD9), but was independent of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. The second mechanism for the killing of opsonized C albicans was strictly dependent on Fcγ receptors, protein kinase C (PKC), and reactive oxygen species production by the NADPH oxidase system. Each of the 2 pathways of Candida killing required Syk tyrosine kinase activity, but dectin-1 was dispensable for both of them. These data provide an explanation for the variable clinical presentation of fungal infection in patients suffering from different immune defects, including dectin-1 deficiency, CARD9 deficiency, or chronic granulomatous disease. PMID:24948657

  1. Members of the Candida parapsilosis Complex and Candida albicans are Differentially Recognized by Human Peripheral Blood Mononuclear Cells

    Science.gov (United States)

    Estrada-Mata, Eine; Navarro-Arias, María J.; Pérez-García, Luis A.; Mellado-Mojica, Erika; López, Mercedes G.; Csonka, Katalin; Gacser, Attila; Mora-Montes, Héctor M.

    2016-01-01

    The systemic infections caused by members of the Candida parapsilosis complex are currently associated to high morbility and mortality rates, and are considered as relevant as those caused by Candida albicans. Since the fungal cell wall is the first point of contact with the host cells, here we performed a comparison of this organelle in members of the C. parapsilosis complex, and its relevance during interaction with human peripheral blood mononuclear cells (PBMCs). We found that the wall of the C. parapsilosis complex members is similar in composition, but differs to that from C. albicans, with less mannan content and more β-glucan and porosity levels. Furthermore, lectin-based analysis showed increased chitin and β1,3-glucan exposure at the surface of C. parapsilosis sensu lato when compared to C. albicans. Yeast cells of members of the C. parapsilosis complex stimulated more cytokine production by human PBMCs than C. albicans cells; and this significantly changed upon removal of O-linked mannans, indicating this wall component plays a significant role in cytokine stimulation by C. parapsilosis sensu lato. When inner wall components were exposed on the wall surface, C. parapsilosis sensu stricto and C. metapsilosis, but not C. orthopsilosis, stimulated higher cytokine production. Moreover, we found a strong dependency on β1,3-glucan recognition for the members of the C. parapsilosis complex, but not for live C. albicans cells; whereas TLR4 was required for TNFα production by the three members of the complex, and stimulation of IL-6 by C. orthopsilosis. Mannose receptor had a significant role during TNFα and IL-1β stimulation by members of the complex. Finally, we demonstrated that purified N- and O-mannans from either C. parapsilosis sensu lato or C. albicans are capable to block the recognition of these pathogens by human PBMCs. Together; our results suggest that the innate immune recognition of the members of the C. parapsilosis complex is differential

  2. Members of the Candida parapsilosis complex and Candida albicans are differentially recognized by human peripheral blood mononuclear cells

    Directory of Open Access Journals (Sweden)

    Eine eEstrada-Mata

    2016-01-01

    Full Text Available The systemic infections caused by members of the Candida parapsilosis complex are currently associated to high mobility and mortality rates, and are considered as relevant as those caused by Candida albicans. Since the fungal cell wall is the first point of contact with the host cells, here we performed a comparison of this organelle in members of the C. parapsilosis complex, and its relevance during interaction with human peripheral blood mononuclear cells. We found that the wall of the C. parapsilosis complex members is similar in composition, but differs to that from C. albicans, with less mannan content and more β-glucan and porosity levels. Furthermore, lectin-based analysis showed increased chitin and β1,3-glucan exposure at the surface of C. parapsilosis sensu lato when compared to C. albicans. Yeast cells of members of the C. parapsilosis complex stimulated more cytokine production by human peripheral blood mononuclear cells than C. albicans cells; and this significantly changed upon removal of O-linked mannans, indicating this wall component plays a significant role in cytokine stimulation by C. parapsilosis sensu lato. When inner wall components were exposed on the wall surface, C. parapsilosis sensu stricto and C. metapsilosis, but not C. orthopsilosis, stimulated higher cytokine production. Moreover, we found a strong dependency on β1,3-glucan recognition for the members of the C. parapsilosis complex, but not for live C. albicans cells; whereas TLR4 was required for TNFα production by the three members of the complex, and stimulation of IL-6 by C. orthopsilosis. Mannose receptor had a significant role during TNF and IL-1β stimulation by members of the complex. Finally, we demonstrated that purified N- and O-mannans from either C. parapsilosis sensu lato or C. albicans are capable to block the recognition of these pathogens by human peripheral blood mononuclear cells. Together; our results suggest that the innate immune

  3. Candida albicans menengitis in a newborn with classical galactosemia

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    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

  4. The ABCs of Candida albicans Multidrug Transporter Cdr1.

    Science.gov (United States)

    Prasad, Rajendra; Banerjee, Atanu; Khandelwal, Nitesh Kumar; Dhamgaye, Sanjiveeni

    2015-12-01

    In the light of multidrug resistance (MDR) among pathogenic microbes and cancer cells, membrane transporters have gained profound clinical significance. Chemotherapeutic failure, by far, has been attributed mainly to the robust and diverse array of these proteins, which are omnipresent in every stratum of the living world. Candida albicans, one of the major fungal pathogens affecting immunocompromised patients, also develops MDR during the course of chemotherapy. The pivotal membrane transporters that C. albicans has exploited as one of the strategies to develop MDR belongs to either the ATP binding cassette (ABC) or the major facilitator superfamily (MFS) class of proteins. The ABC transporter Candida drug resistance 1 protein (Cdr1p) is a major player among these transporters that enables the pathogen to outplay the battery of antifungals encountered by it. The promiscuous Cdr1 protein fulfills the quintessential need of a model to study molecular mechanisms of multidrug transporter regulation and structure-function analyses of asymmetric ABC transporters. In this review, we cover the highlights of two decades of research on Cdr1p that has provided a platform to study its structure-function relationships and regulatory circuitry for a better understanding of MDR not only in yeast but also in other organisms. PMID:26407965

  5. Diorcinol D Exerts Fungicidal Action against Candida albicans through Cytoplasm Membrane Destruction and ROS Accumulation.

    Directory of Open Access Journals (Sweden)

    Ying Li

    Full Text Available Candida albicans, which is the most common human fungal pathogen, causes high mortality among immunocompromised patients. Antifungal drug resistance becomes a major challenge for the management of Candida infection. Diorcinol D (DD, a diphenyl ether derivative isolated from an endolichenic fungus, exerted fungicidal action against Candida species. In this study, we investigated the possible mechanism of its antifungal activity. The change of membrane dynamics and permeability suggested that the cell membrane was disrupted by the treatment of DD. This was further supported by the evidences of intracellular glycerol accumulation, alteration of cell ultrastructure, and down-regulation of genes involved in cell membrane synthesis. In addition, the treatment of C. albicans with DD resulted in the elevation of reactive oxygen species (ROS, which caused the dysfunction of mitochondria. These altogether suggested that DD exerted its antifungal activity through cytoplasmic membrane destruction and ROS accumulation. This finding is helpful to uncover the underlying mechanisms for the diphenyl ether derivatives and provides a potential application in fighting clinical fungal infections.

  6. Fluorometric determination of acid proteinase activity in Candida albicans strains from diabetic patients with vulvovaginal candidiasis.

    Science.gov (United States)

    Yildirim, Zuhal; Kilic, Nedret; Kalkanci, Ayse

    2011-09-01

    Vulvovaginal candidiasis is one of the most frequent disorders in obstetrics and gynaecology. Approximately three-quarters of all adult women experience at least one episode of vulvovaginal candidiasis during their life span. Diabetes mellitus (DM) increases the rate of vaginal colonisation and infection with Candida species. The secreted acid proteinase might be especially relevant in the pathogenesis of vulvovaginal candidiasis. The aim of this study was to determine the acid proteinase activity in the samples of Candida albicans from diabetic patients with vulvovaginal candidiasis by a fluorometric method. Vaginal swabs were taken from 33 women (aged between 22 and 57 years) having symptoms of vaginitis. Patients were divided into three groups: control group, controlled diabetic group and uncontrolled diabetic group. The proteinase activity in the culture supernatants was determined by a modified fluorometric method. Acid proteinase activities were significantly increased in the uncontrolled diabetic group in comparison with both the control group and the controlled diabetic group (P albicans pathogenesis in diabetic patients. Improving glucose control may reduce the risk of Candida colonisation and potentially symptomatic infection, among women with diabetes and hence may be useful even for weaker enzyme activity measurements.

  7. Mast cells phagocyte Candida albicans and produce nitric oxide by mechanisms involving TLR2 and Dectin-1.

    Science.gov (United States)

    Pinke, Karen Henriette; Lima, Heliton Gustavo de; Cunha, Fernando Queiroz; Lara, Vanessa Soares

    2016-02-01

    Candida albicans (C. albicans) is a fungus commonly found in the human mucosa, which may cause superficial and systemic infections, especially in immunosuppression. Until now, the main actors in the defense against this fungus are the epithelial cells, neutrophils, macrophages/monocytes and dendritic cells. However, mast cells are strategically located to play a first line of anti-Candida defense and it has appropriate mechanisms to do it. As with other cells, the recognition of C. albicans occurs meanly via TLR2 and Dectin-1. We assess the TLR2/Dectin-1 involvement in phagocytosis and production of nitric oxide (NO) and reactive oxygen species (ROS) by mast cells challenged with C. albicans. Bone marrow-derived mast cells (MC) from wild type (Wt) or knockout (TLR2-/-) mice C57BL/6 were subjected to in vitro Dectin-1 blockade. After challenged with FITC-labeled C. albicans or zymosan, phagocytosis was analyzed by microscopy. The intracellular production of NO and ROS was measured by DAF-FM diacetate and CellROX Deep/Red Reagent kits. The nitrite formation and hydrogen peroxide release were analyzed by Griess reaction and Amplex Red Hydrogen Peroxide/Peroxidase Assay Kit. Wt/MC phagocytose C. albicans with production of intracellular NO, but not ROS. Moreover, increased levels of nitrite were also observed. The absence and/or blockade of TLR2/Dectin-1 caused significant decreased in C. albicans phagocytosis and NO production. Our results showed that mast cells are able to phagocytose and produce NO against C. albicans via TLR2/Dectin-1. Therefore, mast cells could be important during the course of Candida infection and as a therapeutic target.

  8. Mast cells phagocyte Candida albicans and produce nitric oxide by mechanisms involving TLR2 and Dectin-1.

    Science.gov (United States)

    Pinke, Karen Henriette; Lima, Heliton Gustavo de; Cunha, Fernando Queiroz; Lara, Vanessa Soares

    2016-02-01

    Candida albicans (C. albicans) is a fungus commonly found in the human mucosa, which may cause superficial and systemic infections, especially in immunosuppression. Until now, the main actors in the defense against this fungus are the epithelial cells, neutrophils, macrophages/monocytes and dendritic cells. However, mast cells are strategically located to play a first line of anti-Candida defense and it has appropriate mechanisms to do it. As with other cells, the recognition of C. albicans occurs meanly via TLR2 and Dectin-1. We assess the TLR2/Dectin-1 involvement in phagocytosis and production of nitric oxide (NO) and reactive oxygen species (ROS) by mast cells challenged with C. albicans. Bone marrow-derived mast cells (MC) from wild type (Wt) or knockout (TLR2-/-) mice C57BL/6 were subjected to in vitro Dectin-1 blockade. After challenged with FITC-labeled C. albicans or zymosan, phagocytosis was analyzed by microscopy. The intracellular production of NO and ROS was measured by DAF-FM diacetate and CellROX Deep/Red Reagent kits. The nitrite formation and hydrogen peroxide release were analyzed by Griess reaction and Amplex Red Hydrogen Peroxide/Peroxidase Assay Kit. Wt/MC phagocytose C. albicans with production of intracellular NO, but not ROS. Moreover, increased levels of nitrite were also observed. The absence and/or blockade of TLR2/Dectin-1 caused significant decreased in C. albicans phagocytosis and NO production. Our results showed that mast cells are able to phagocytose and produce NO against C. albicans via TLR2/Dectin-1. Therefore, mast cells could be important during the course of Candida infection and as a therapeutic target. PMID:26421959

  9. Potent Synergy between Spirocyclic Pyrrolidinoindolinones and Fluconazole against Candida albicans.

    Science.gov (United States)

    Premachandra, Ilandari Dewage Udara Anulal; Scott, Kevin A; Shen, Chengtian; Wang, Fuqiang; Lane, Shelley; Liu, Haoping; Van Vranken, David L

    2015-10-01

    A spiroindolinone, (1S,3R,3aR,6aS)-1-benzyl-6'-chloro-5-(4-fluorophenyl)-7'-methylspiro[1,2,3a,6a-tetrahydropyrrolo[3,4-c]pyrrole-3,3'-1H-indole]-2',4,6-trione, was previously reported to enhance the antifungal effect of fluconazole against Candida albicans. A diastereomer of this compound was synthesized, along with various analogues. Many of the compounds were shown to enhance the antifungal effect of fluconazole against C. albicans, some with exquisite potency. One spirocyclic piperazine derivative, which we have named synazo-1, was found to enhance the effect of fluconazole with an EC50 value of 300 pM against a susceptible strain of C. albicans and going as low as 2 nM against some resistant strains. Synazo-1 exhibits true synergy with fluconazole, with an FIC index below 0.5 in the strains tested. Synazo-1 exhibited low toxicity in mammalian cells relative to the concentrations required for antifungal synergy.

  10. Distribution of Candida albicans genotypes among family members

    Science.gov (United States)

    Mehta, S. K.; Stevens, D. A.; Mishra, S. K.; Feroze, F.; Pierson, D. L.

    1999-01-01

    Thirty-three families (71 subjects) were screened for the presence of Candida albicans in mouthwash or stool specimens; 12 families (28 subjects) were culture-positive for this yeast. An enrichment procedure provided a twofold increase in the recovery of C. albicans from mouthwash specimens. Nine of the twelve culture-positive families had two positive members each, two families had three positive members each, and one family had four positive members. Genetic profiles were obtained by three methods: pulsed-field gel electrophoresis; restriction endonuclease analysis, and random amplification of polymorphic DNA analysis. DNA fingerprinting of C. albicans isolated from one body site three consecutive times revealed that each of the 12 families carried a distinct genotype. No two families shared the same strain, and two or more members of a family commonly shared the same strain. Intrafamily genotypic identity (i.e., each member within the family harbored the same strain) was demonstrated in six families. Genotypes of isolates from husband and wife differed from one another in five families. All three methods were satisfactory in determining genotypes; however, we concluded that restriction endonuclease analysis provided adequate resolving power.

  11. Candida albicans biofilm on titanium: effect of peroxidase precoating

    Directory of Open Access Journals (Sweden)

    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

  12. Antimicrobial activity of calcium hydroxide and chlorhexidine on intratubular Candida albicans

    OpenAIRE

    Jacques Rezende Delgado, Ronan; Helena Gasparoto, Thaís; Renata Sipert, Carla; Ramos Pinheiro, Claudia; Gomes de Moraes, Ivaldo; Brandão Garcia, Roberto; Antônio Hungaro Duarte, Marco; Monteiro Bramante, Clóvis; Aparecido Torres, Sérgio; Pompermaier Garlet, Gustavo; Paula Campanelli, Ana; Bernardineli, Norberti

    2013-01-01

    This study investigated the efficacy of calcium hydroxide and chlorhexidine gel for the elimination of intratubular Candida albicans (C. albicans). Human single-rooted teeth contaminated with C. albicans were treated with calcium hydroxide, 2% chlorhexidine gel, calcium hydroxide plus 2% chlorhexidine gel, or saline (0.9% sodium chloride) as a positive control. The samples obtained at depths of 0–100 and 100–200 µm from the root canal system were analyzed for C. albicans load by counting the ...

  13. Genetic susceptibility to Candida infections

    OpenAIRE

    Smeekens, S P; Veerdonk, F.L. van de; Kullberg, B J; Netea, M.G.

    2013-01-01

    Candida spp. are medically important fungi causing severe mucosal and life-threatening invasive infections, especially in immunocompromised hosts. However, not all individuals at risk develop Candida infections, and it is believed that genetic variation plays an important role in host susceptibility. On the one hand, severe fungal infections are associated with monogenic primary immunodeficiencies such as defects in STAT1, STAT3 or CARD9, recently discovered as novel clinical entities. On the...

  14. 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.

  15. Candida infections : detection and epidemiology

    NARCIS (Netherlands)

    Borst, A. (Annemarie)

    2002-01-01

    Despite the fact that the yeast Candida is the number 4 cause of bloodstream infections in the United States and ranks number 8 in Europe, adequate detection methods are lacking. Furthermore, relatively little is known about the epidemiology of Candida. Our aim was to improve the detection and ident

  16. Quinacrine inhibits Candida albicans growth and filamentation at neutral pH.

    Science.gov (United States)

    Kulkarny, Vibhati V; Chavez-Dozal, Alba; Rane, Hallie S; Jahng, Maximillian; Bernardo, Stella M; Parra, Karlett J; Lee, Samuel A

    2014-12-01

    Candida albicans is a common cause of catheter-related bloodstream infections (CR-BSI), in part due to its strong propensity to form biofilms. Drug repurposing is an approach that might identify agents that are able to overcome antifungal drug resistance within biofilms. Quinacrine (QNC) is clinically active against the eukaryotic protozoan parasites Plasmodium and Giardia. We sought to investigate the antifungal activity of QNC against C. albicans biofilms. C. albicans biofilms were incubated with QNC at serially increasing concentrations (4 to 2,048 μg/ml) and assessed using a 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay in a static microplate model. Combinations of QNC and standard antifungals were assayed using biofilm checkerboard analyses. To define a mechanism of action, QNC was assessed for the inhibition of filamentation, effects on endocytosis, and pH-dependent activity. High-dose QNC was effective for the prevention and treatment of C. albicans biofilms in vitro. QNC with fluconazole had no interaction, while the combination of QNC and either caspofungin or amphotericin B demonstrated synergy. QNC was most active against planktonic growth at alkaline pH. QNC dramatically inhibited filamentation. QNC accumulated within vacuoles as expected and caused defects in endocytosis. A tetracycline-regulated VMA3 mutant lacking vacuolar ATPase (V-ATPase) function demonstrated increased susceptibility to QNC. These experiments indicate that QNC is active against C. albicans growth in a pH-dependent manner. Although QNC activity is not biofilm specific, QNC is effective in the prevention and treatment of biofilms. QNC antibiofilm activity likely occurs via several independent mechanisms: vacuolar alkalinization, inhibition of endocytosis, and impaired filamentation. Further investigation of QNC for the treatment and prevention of biofilm-related Candida CR-BSI is warranted. PMID:25288082

  17. Diferenciação de cepas de Candida albicans pelo sistema killer

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    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. In Vitro and In Vivo Antifungal Activity of Lichochalcone-A against Candida albicans Biofilms

    Science.gov (United States)

    Seleem, Dalia; Benso, Bruna; Noguti, Juliana; Pardi, Vanessa; Murata, Ramiro Mendonça

    2016-01-01

    Oral candidiasis (OC) is an opportunistic fungal infection with high prevalence among immunocompromised patients. Candida albicans is the most common fungal pathogen responsible for OC, often manifested in denture stomatitis and oral thrush. Virulence factors, such as biofilms formation and secretion of proteolytic enzymes, are key components in the pathogenicity of C. albicans. Given the limited number of available antifungal therapies and the increase in antifungal resistance, demand the search for new safe and effective antifungal treatments. Lichochalcone-A is a polyphenol natural compound, known for its broad protective activities, as an antimicrobial agent. In this study, we investigated the antifungal activity of lichochalcone-A against C. albicans biofilms both in vitro and in vivo. Lichochalcone-A (625 μM; equivalent to 10x MIC) significantly reduced C. albicans (MYA 2876) biofilm growth compared to the vehicle control group (1% ethanol), as indicated by the reduction in the colony formation unit (CFU)/ml/g of biofilm dry weight. Furthermore, proteolytic enzymatic activities of proteinases and phospholipases, secreted by C. albicans were significantly decreased in the lichochalcone-A treated biofilms. In vivo model utilized longitudinal imaging of OC fungal load using a bioluminescent-engineered C. albicans (SKCa23-ActgLUC) and coelenterazine substrate. Mice treated with lichochalcone-A topical treatments exhibited a significant reduction in total photon flux over 4 and 5 days post-infection. Similarly, ex vivo analysis of tongue samples, showed a significant decrease in CFU/ml/mg in tongue tissue sample of lichochalcone-A treated group, which suggest the potential of lichochalcone-A as a novel antifungal agent for future clinical use. PMID:27284694

  19. Rapid detection of Candida albicans by polymerase spiral reaction assay in clinical blood samples

    Directory of Open Access Journals (Sweden)

    Xiaoqun eJiang

    2016-06-01

    Full Text Available Candida albicans is the most common human yeast pathogen which causes mucosal infections and invasive fungal diseases. Early detection of this pathogen is needed to guide preventative and therapeutic treatment. The aim of this study was to establish a polymerase spiral reaction (PSR assay that rapidly and accurately detects C. albicans and to assess the clinical applicability of PSR-based diagnostic testing. Internal transcribed spacer 2 (ITS2, a region between 5.8S and 28S fungal ribosomal DNA, was used as the target sequence. Four primers were designed for amplification of ITS2 with the PSR method, which was evaluated using real time turbidity monitoring and visual detection using a pH indicator. Fourteen non- C. albicans yeast strains were negative for detection, which indicated the specificity of PSR assay was 100%. A 10-fold serial dilution of C. albicans genomic DNA was subjected to PSR and conventional PCR to compare their sensitivities. The detection limit of PSR was 6.9 pg/µl within 1 h, 10-fold higher than that of PCR (69.0 pg/µl. Blood samples (n=122 were collected from intensive care unit and hematological patients with proven or suspected C. albicans infection at two hospitals in Beijing, China. Both PSR assay and the culture method were used to analyze the samples. Of the 122 clinical samples, 34 were identified as positive by PSR. The result was consistent with those obtained by the culture method. In conclusion, a novel and effective C. albicans detection assay was developed that has a great potential for clinical screening and point-of-care testing.

  20. Total Protein Profile and Drug Resistance in Candida albicans Isolated from Clinical Samples

    Directory of Open Access Journals (Sweden)

    Kamal Uddin Zaidi

    2016-01-01

    Full Text Available This study was done to assess the antifungal susceptibility of clinical isolates of Candida albicans and to evaluate its total protein profile based on morphological difference on drug resistance. Hundred and twenty clinical isolates of C. albicans from various clinical specimens were tested for susceptibility against four antifungal agents, namely, fluconazole, itraconazole, amphotericin B, and ketoconazole. A significant increase of drug resistance in clinical isolates of C. albicans was observed. The study showed 50% fluconazole and itraconazole resistance at 32 μg mL−1 with a MIC50 and MIC90 values at 34 and 47 and 36 and 49 μg mL−1, respectively. All isolates were sensitive to amphotericin B and ketoconazole. The SDS-PAGE protein profile showed a prevalent band of ~52.5 kDa, indicating overexpression of gene in 72% strains with fluconazole resistance. Since the opportunistic infections of Candida spp. are increasing along with drug resistance, the total protein profile will help in understanding the evolutionary changes in drug resistance and also to characterize them.

  1. Effects of Mentha suaveolens Essential Oil Alone or in Combination with Other Drugs in Candida albicans.

    Science.gov (United States)

    Stringaro, Annarita; Vavala, Elisabetta; Colone, Marisa; Pepi, Federico; Mignogna, Giuseppina; Garzoli, Stefania; Cecchetti, Serena; Ragno, Rino; Angiolella, Letizia

    2014-01-01

    Candidosis is the most important cause of fungal infections in humans. The yeast Candida albicans can form biofilms, and it is known that microbial biofilms play an important role in human diseases and are very difficult to treat. The prolonged treatment with drugs has often resulted in failure and resistance. Due to the emergence of multidrug resistance, alternatives to conventional antimicrobial therapy are needed. This study aims to analyse the effects induced by essential oil of Mentha suaveolens Ehrh (EOMS) on Candida albicans and its potential synergism when used in combination with conventional drugs. Morphological differences between control and EOMS treated yeast cells or biofilms were observed by scanning electron microscopy and transmission electron microscopy (SEM and TEM resp.,). In order to reveal the presence of cell cycle alterations, flow cytometry analysis was carried out as well. The synergic action of EOMS was studied with the checkerboard method, and the cellular damage induced by different treatments was analysed by TEM. The results obtained have demonstrated both the effects of EOMS on C. albicans yeast cells and biofilms and the synergism of EOMS when used in combination with conventional antifungal drugs as fluconazole (FLC) and micafungin (MCFG), and therefore we can hypothesize on its potential use in therapy. Further studies are necessary to know its mechanism of action.

  2. 中草药抗白念珠菌作用研究进展%Research progress of Chinese herbal medicine against Candida albicans

    Institute of Scientific and Technical Information of China (English)

    李姝毅; 夏志宽; 杨蓉娅

    2013-01-01

    Candida albicans is one of the most common human fungal pathogen,which can cause a variety of superficial and deep mycoses,and often become resistant to commonly used antifungal agents.So looking for broad-spectrum,high efficiency,low toxicity anti-Candida drugs has became a hot research.Extremely rich resources of Chinese herbal medicine have certain advantages of the prevention and treatment of Candida infections.To study the role of Chinese herbal medicine against Candida albicans,articles summarize the three aspects:herbal mechanism of action against Candida albicans and its active ingredient,single herb and compound herbal preparations against Candida albicans,synergistic effect of compound traditional Chinese medicine and western medicine against Candida albicans.The Chinese herbal medicine against Candida albicans clinical and experimental studies in recent years were reviewed.The article further confirmed the role of herbal anti-Candida albicans and showed the broad application prospects of herbal antifungal aspects.%白念珠菌,是人类最常见的真菌病原体,可引起各种浅表及深部真菌病,对常用抗真菌药物易产生耐药.文章就近年来有关中草药抗白念珠菌的相关临床及实验研究进行综述,主要从中草药抗白念珠菌的作用机制及其活性成分、单味及复方中草药制剂抗白念珠菌作用、中西药协同抗白念珠菌作用几个方面进行阐述.

  3. 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.

  4. Role of CaECM25 in cell morphogenesis, cell growth and virulence in Candida albicans

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Candida albicans is the most prominent opportunistic fungal pathogen in humans. Multiple factors are associated with the virulence of C. albicans, including morphogenesis, cell wall organization and growth rate. Here, we describe the identification and functional characterization of CaECM25, a gene that has not been reported before. We constructed Caecm25?/? mutants and investigated the role of the gene in morphogenesis, cell wall organization and virulence. CaECM25 deletion resulted in defects in cell separation, a slower growth rate, reduced filamentous growth and attenuated adherence to plastic surfaces. The Caecm25?/? mutant was also significantly less virulent than wild type when tested for systemic infection in mice. Therefore, CaECM25 plays important roles in morphogenesis, cell wall organization and virulence.

  5. Role of CaECM25 in cell morphogenesis, cell growth and virulence in Candida albicans

    Institute of Scientific and Technical Information of China (English)

    ZHANG TingTing; LI WanJie; LI Di; WANG Yue; SANG JianLi

    2008-01-01

    Candida albicans is the most prominent opportunistic fungal pathogen in humans. Multiple factors are associated with the virulence of C. albicans, including morphogenesis, cell wall organization and growth rate. Here, we describe the identification and functional characterization of CaECM25, a gene that has not been reported before. We constructed Caecm25△/△ mutants and investigated the role of the gene In morphogenesis, cell wall organization and virulence. CaECM25 deletion resulted in defects in cell separation, a slower growth rate, reduced filamentous growth and attenuated adherence to plastic surfaces. The Caecm25△/△ mutant was also significantly less virulent than wild type when tested for systemic infection in mice. Therefore, CaECM25 plays important roles in morphogenesis, cell wall organization and virulence.

  6. Candida albicans osteomyelitis as a cause of chest pain and visual loss.

    Science.gov (United States)

    Magano, Rita; Cortez, Joana; Ramos, Evelise; Trindade, Luís

    2015-01-01

    Candida albicans osteomyelitis is a rare disease that occurs in immunocompromised individuals, sometimes with a late diagnosis related to the mismatch between symptoms and candidemia. This case refers to a 36-year-old male patient with a history of oesophageal surgery for achalasia with multiple subsequent surgeries and hospitalisation in the intensive care unit for oesophageal fistula complication. Four months after discharge, the patient was admitted to the infectious diseases department with pain in the 10th-12th left ribs, swelling of the 4th-6th costal cartilage and decreased visual acuity. An MRI study showed thickening and diffuse enhancement, with no defined borders in the cartilage and ribs, compatible with infection. After performing a CT-guided bone biopsy, isolated C. albicans sensitive to antifungal agents was detected. The patient started therapy with liposomal amphotericin B and maintenance fluconazole for 6 months and showed clinical and radiological improvement within this time. PMID:26475877

  7. Candida albicans and Candida parapsilosis induce different T-cell responses in human peripheral blood mononuclear cells

    NARCIS (Netherlands)

    Toth, A.; Csonka, K.; Jacobs, C.; Vagvolgyi, C.; Nosanchuk, J.D.; Netea, M.G.; Gacser, A.

    2013-01-01

    Candida parapsilosis is the third most frequent cause of candidemia. Despite its clinical importance, little is known about the human immunological response to C. parapsilosis. In this study, we compared the cytokine responses evoked by Candida albicans and C. parapsilosis. C. parapsilosis-stimulate

  8. Wild-type Drosophila melanogaster as a model host to analyze nitrogen source dependent virulence of Candida albicans.

    Directory of Open Access Journals (Sweden)

    Monica M Davis

    Full Text Available The fungal pathogen Candida albicans is a common cause of opportunistic infections in humans. We report that wild-type Drosophila melanogaster (OrR flies are susceptible to virulent C. albicans infections and have established experimental conditions that enable OrR flies to serve as model hosts for studying C. albicans virulence. After injection into the thorax, wild-type C. albicans cells disseminate and invade tissues throughout the fly, leading to lethality. Similar to results obtained monitoring systemic infections in mice, well-characterized cph1Δ efg1Δ and csh3Δ fungal mutants exhibit attenuated virulence in flies. Using the OrR fly host model, we assessed the virulence of C. albicans strains individually lacking functional components of the SPS sensing pathway. In response to extracellular amino acids, the plasma membrane localized SPS-sensor (Ssy1, Ptr3, and Ssy5 activates two transcription factors (Stp1 and Stp2 to differentially control two distinct modes of nitrogen acquisition (host protein catabolism and amino acid uptake, respectively. Our results indicate that a functional SPS-sensor and Stp1 controlled genes required for host protein catabolism and utilization, including the major secreted aspartyl protease SAP2, are required to establish virulent infections. By contrast, Stp2, which activates genes required for amino acid uptake, is dispensable for virulence. These results indicate that nutrient availability within infected hosts directly influences C. albicans virulence.

  9. Synergistic combinations of antifungals and antivirulence agents to fight against Candida albicans

    DEFF Research Database (Denmark)

    Cui, Jinhui; Ren, Biao; Tong, Yaojun;

    2015-01-01

    -drug resistance, demand innovative strategies for new effective antifungal drugs. Synergistic combinations of antifungals and anti-virulence agents highlight the pragmatic strategy to reduce the development of drug resistant and potentially repurpose known antifungals, which bypass the costly and time......Candida albicans, one of the pathogenic Candida species, causes high mortality rate in immunocompromised and high-risk surgical patients. In the last decade, only one new class of antifungal drug echinocandin was applied. The increased therapy failures, such as the one caused by multi......-consuming pipeline of new drug development. Anti-virulence and synergistic combination provide new options for antifungal drug discovery by counteracting the difficulty or failure of traditional therapy for fungal infections....

  10. Characteristics of Candida albicans biofilms grown in a synthetic urine medium.

    Science.gov (United States)

    Uppuluri, Priya; Dinakaran, Hemamalini; Thomas, Derek P; Chaturvedi, Ashok K; Lopez-Ribot, Jose L

    2009-12-01

    Urinary tract infections (UTIs) are the most common type of nosocomial infection, and Candida albicans is the most frequent organism causing fungal UTIs. Presence of an indwelling urinary catheter represents a significant risk factor for UTIs. Furthermore, these infections are frequently associated with the formation of biofilms on the surface of these catheters. Here, we describe the characterization of C. albicans biofilms formed in vitro using synthetic urine (SU) medium and the frequently used RPMI medium and compare the results. Biofilms of C. albicans strain SC5314 were formed in 96-well microtiter plates and on silicon elastomer pieces using both SU and RPMI media. Biofilm formation was monitored by microscopy and a colorimetric XTT [2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] reduction assay. As in biofilms grown in RPMI medium, time course studies revealed that biofilm formation using SU medium occurred after an initial adherence phase, followed by growth, proliferation, and maturation. However, microscopy techniques revealed that the architectural complexity of biofilms formed in SU medium was lower than that observed for those formed using RPMI medium. In particular, the level of filamentation of cells within the biofilms formed in SU medium was diminished compared to those in the biofilms grown in RPMI medium. This observation was also corroborated by expression profiling of five filamentation-associated genes using quantitative real-time reverse transcriptase PCR. Sessile C. albicans cells were resistant to fluconazole and amphotericin B, irrespective of the medium used to form the biofilms. However, caspofungin exhibited potent in vitro activity at therapeutic levels against C. albicans biofilms grown in both SU and RPMI media.

  11. The Candida genome database incorporates multiple Candida species: multispecies search and analysis tools with curated gene and protein information for Candida albicans and Candida glabrata.

    Science.gov (United States)

    Inglis, Diane O; Arnaud, Martha B; Binkley, Jonathan; Shah, Prachi; Skrzypek, Marek S; Wymore, Farrell; Binkley, Gail; Miyasato, Stuart R; Simison, Matt; Sherlock, Gavin

    2012-01-01

    The Candida Genome Database (CGD, http://www.candidagenome.org/) is an internet-based resource that provides centralized access to genomic sequence data and manually curated functional information about genes and proteins of the fungal pathogen Candida albicans and other Candida species. As the scope of Candida research, and the number of sequenced strains and related species, has grown in recent years, the need for expanded genomic resources has also grown. To answer this need, CGD has expanded beyond storing data solely for C. albicans, now integrating data from multiple species. Herein we describe the incorporation of this multispecies information, which includes curated gene information and the reference sequence for C. glabrata, as well as orthology relationships that interconnect Locus Summary pages, allowing easy navigation between genes of C. albicans and C. glabrata. These orthology relationships are also used to predict GO annotations of their products. We have also added protein information pages that display domains, structural information and physicochemical properties; bibliographic pages highlighting important topic areas in Candida biology; and a laboratory strain lineage page that describes the lineage of commonly used laboratory strains. All of these data are freely available at http://www.candidagenome.org/. We welcome feedback from the research community at candida-curator@lists.stanford.edu.

  12. Epithelial discrimination of commensal and pathogenic Candida albicans.

    Science.gov (United States)

    Tang, S X; Moyes, D L; Richardson, J P; Blagojevic, M; Naglik, J R

    2016-04-01

    All mucosal surfaces are lined by epithelial cells and are colonised by opportunistic microbes. In health, these opportunistic microbes remain commensal and are tolerated by the immune system. However, when the correct environmental conditions arise, these microbes can become pathogenic and need to be controlled or cleared by the immune system to prevent disease. The mechanisms that enable epithelial cells to initiate the 'danger' signals activated specifically by pathogenic microbes are critical to mucosal defence and homeostasis but are not well understood. Deciphering these mechanisms will provide essential understanding to how mucosal tissues maintain health and activate immunity, as well as how pathogens promote disease. This review focuses on the interaction of the human fungal pathogen Candida albicans with epithelial cells and the epithelial mechanisms that enable mucosal tissues to discriminate between the commensal and pathogenic state of this medically important fungus. PMID:26843519

  13. Purification and germination of Candida albicans and Candida dubliniensis chlamydospores cultured in liquid media.

    LENUS (Irish Health Repository)

    Citiulo, Francesco

    2009-10-01

    Candida albicans and Candida dubliniensis are the only Candida sp. that have been observed to produce chlamydospores. The function of these large, thick-walled cells is currently unknown. In this report, we describe the production and purification of chlamydospores from these species in defined liquid media. Staining with the fluorescent dye FUN-1 indicated that chlamydospores are metabolically active cells, but that metabolic activity is undetectable in chlamydospores that are >30 days old. However, 5-15-day-old chlamydospores could be induced to produce daughter chlamydospores, blastospores, pseudohyphae and true hyphae depending on the incubation conditions used. Chlamydospores that were preinduced to germinate were also observed to escape from murine macrophages following phagocytosis, suggesting that these structures may be viable in vivo. Mycelium-attached and purified chlamydospores rapidly lost their viability in water and when subjected to dry stress, suggesting that they are unlikely to act as long-term storage structures. Instead, our data suggest that chlamydospores represent an alternative specialized form of growth by C. albicans and C. dubliniensis.

  14. Fungistatic activity of all-trans retinoic acid against Aspergillus fumigatus and Candida albicans

    Science.gov (United States)

    Campione, Elena; Gaziano, Roberta; Marino, Daniele; Orlandi, Augusto

    2016-01-01

    Purpose Fungal infections are a major complication in hematologic and neoplastic patients causing severe morbidity and mortality. Aspergillus fumigatus and Candida albicans are among the most invasive opportunistic pathogens in immunocompromised patients, and classic antifungal drugs are frequently unsuccessful in these patients. Recent reports hypothesize that the antifungal efficacy of all-trans retinoic acid (ATRA) is mainly related to its strong capacity to stimulate monocyte-mediated immunity, but no consideration was given to its potential direct fungistatic activity. Moreover, ATRA offers the opportunity for systemic therapy. Methods and results We investigated the efficacy of ATRA at different concentrations for its antifungal activity against opportunistic A. fumigatus and C. albicans obtained from clinical samples according to standard protocols. A fungistatic activity of ATRA on A. fumigatus and C. albicans at 0.5–1 mM concentration was documented up to 7 days. Conclusion This is the first evidence of a direct and strong fungistatic activity of ATRA against A. fumigatus and C. albicans. The potential adjuvant therapeutic application of ATRA might be useful in the treatment and/or prevention of systemic mycoses in immunocompromised patients. The discovery of a direct fungistatic activity, in association with its reported immunomodulatory properties, makes ATRA an excellent candidate for new combined antifungal strategies for systemic mycoses in immunocompromised and cancer patients. PMID:27199548

  15. Hubungan Kadar Glukosa Darah dengan Pertumbuhan Candida Albicans pada Penderita Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Sri Hernawati

    2015-10-01

    Full Text Available Diabetes mellitus is comma only hereditary metabolic disorder. The signs were hyperglycemic and glucosuric with or without acute or chronic clinically symptoms. It was cause effectively insulin deficiency. The primary was carbohydrate metabolism disorder which followed lipid and protein metabolism disorders. The increase of boold. Glucose conentration could increase salivary glucose concentration. Glucose was a good media for the growth of microorganism, for example: candida albicans. The most frequently infection on oral mucous diabetes mellitus patients was candidacies. The purpose of the study was to determine the relation of blood glucose concentration and C. albicans growth on oral cavity diabetes mellitus patients. The subject consisted of 8 non regulated diabetes mellitus, 8 regulated diabetes mellitus, and 8 normal patients, respectively. The assessment of blood glucose concentration used Bio-Rad Diastat Halmoglobine A1c method. The growth of C. albicans was determined using swab on oral mucous. The result of swab was into culated on sabaurond agar, than gram stining and glucose test was done. Data was analyzed using spearman test. The result indicated that the growth of C. albicans was eughen on non regulated diabetes mellitus than regulated diabetes mellitus. It's also on regulated diabetes mellitus that normal patient.

  16. Effect of ethanolic extract of Ecballium elaterium against Staphylococcus aureus and Candida albicans

    Institute of Scientific and Technical Information of China (English)

    Ghaleb Adwan; Yousef Salameh; Kamel Adwan

    2011-01-01

    To evaluate the antimicrobial activity of ethanolic extract of Ecballium elaterium (E.elaterium) fruits alone against Staphylococcus aureus (S. aureus) strains and Candida albicans (C. albicans) strains, or in combination with penicillin against Staphylococcus areus strains. Methods: Evaluation of the antimicrobial activity or synergy interaction was carried out using microdilution method. Results: The results showed that ethanolic extract of E. elaterium fruits has antimicrobial activity against methicillin resistant S. aureus (MRSA), methicillin sensitive S.aureus (MSSA) and C. albicans. This extract showed a significant decrease in minimum inhibitory concentrations (MIC) of penicillin against both MRSA and MSSA strains. Fractional inhibitory concentration index (FIC) between penicillin and ethanolic extract of E. elaterium fruits against these test strains was less than 0.5. Conclusions: This study suggests that ethanolic extract of E. elaterium fruits has antimicrobial activity against S. aureus and C. albicans and there is a possibility of concurrent use of penicillin and E. elaterium extract in combination in the treatment of infections caused by MRSA and MSSA strains. A wider study is needed to identify the effective components, the mode of action and the possible toxic effect in vivo of these ingredients.

  17. Efficacy of ferulic acid encapsulated chitosan nanoparticles against Candida albicans biofilm.

    Science.gov (United States)

    Panwar, Richa; Pemmaraju, Suma C; Sharma, Asvene K; Pruthi, Vikas

    2016-06-01

    Candida albicans, an opportunistic fungal pathogen is a major causative agent of superficial to systemic life-threating biofilm infections on indwelling medical devices. These biofilms acts as double edge swords owing to their resistance towards antibiotics and immunological barriers. To overcome this threat ferulic acid encapsulated chitosan nanoparticles (FA-CSNPs) were formulated to assess its efficacy as an antibiofilm agent against C. albicans. These FA-CSNPs were synthesized using ionotropic gelation method and observed through field emission scanning electron microscopy (FESEM) and fluorescent microscopy. Assessment of successful encapsulation and stability of ferulic acid into chitosan nanoparticles was made using Fourier transform infrared spectrum (FTIR), (1)H NMR and thermal analyses. Synthesized FA-CSNPs, were found to be cytocompatible, when tested using Human Embryonic Kidney (HEK-293) cell lines. XTT assay revealed that FA-CSNPs reduced the cell metabolic activity of C. albicans upto 22.5% as compared to native ferulic acid (63%) and unloaded CSNPs (88%) after 24 h incubation. Disruption of C. albicans biofilm architecture was visualized by FESEM. Results highlighted the potential of FA-CSNPs to be used as an effective alternative to the conventional antifungal therapeutics. PMID:26930164

  18. Probiotic lactobacilli inhibit early stages of Candida albicans biofilm development by reducing their growth, cell adhesion, and filamentation.

    Science.gov (United States)

    Matsubara, Victor Haruo; Wang, Yi; Bandara, H M H N; Mayer, Marcia Pinto Alves; Samaranayake, Lakshman P

    2016-07-01

    We evaluated the inhibitory effects of the probiotic Lactobacillus species on different phases of Candida albicans biofilm development. Quantification of biofilm growth and ultrastructural analyses were performed on C. albicans biofilms treated with Lactobacillus rhamnosus, Lactobacillus casei, and Lactobacillus acidophilus planktonic cell suspensions as well as their supernatants. Planktonic lactobacilli induced a significant reduction (p  0.05), but significantly reduced the early stages of Candida biofilm formation (p lactobacilli negatively impacted C. albicans yeast-to-hyphae differentiation and biofilm formation. The inhibitory effects of the probiotic Lactobacillus on C. albicans entailed both cell-cell interactions and secretion of exometabolites that may impact on pathogenic attributes associated with C. albicans colonization on host surfaces and yeast filamentation. This study clarifies, for the first time, the mechanics of how Lactobacillus species may antagonize C. albicans host colonization. Our data elucidate the inhibitory mechanisms that define the probiotic candicidal activity of lactobacilli, thus supporting their utility as an adjunctive therapeutic mode against mucosal candidal infections.

  19. Global screening of potential Candida albicans biofilm-related transcription factors via network comparison

    Directory of Open Access Journals (Sweden)

    Murillo Luis A

    2010-01-01

    Full Text Available Abstract Background Candida albicans is a commonly encountered fungal pathogen in humans. The formation of biofilm is a major virulence factor in C. albicans pathogenesis and is related to antidrug resistance of this organism. Although many factors affecting biofilm have been analyzed, molecular mechanisms that regulate biofilm formation still await to be elucidated. Results In this study, from the gene regulatory network perspective, we developed an efficient computational framework, which integrates different kinds of data from genome-scale analysis, for global screening of potential transcription factors (TFs controlling C. albicans biofilm formation. S. cerevisiae information and ortholog data were used to infer the possible TF-gene regulatory associations in C. albicans. Based on TF-gene regulatory associations and gene expression profiles, a stochastic dynamic model was employed to reconstruct the gene regulatory networks of C. albicans biofilm and planktonic cells. The two networks were then compared and a score of relevance value (RV was proposed to determine and assign the quantity of correlation of each potential TF with biofilm formation. A total of twenty-three TFs are identified to be related to the biofilm formation; ten of them are previously reported by literature evidences. Conclusions The results indicate that the proposed screening method can successfully identify most known biofilm-related TFs and also identify many others that have not been previously reported. Together, this method can be employed as a pre-experiment screening approach that reveals new target genes for further characterization to understand the regulatory mechanisms in biofilm formation, which can serve as the starting point for therapeutic intervention of C. albicans infections.

  20. An expanded regulatory network temporally controls Candida albicans biofilm formation.

    Science.gov (United States)

    Fox, Emily P; Bui, Catherine K; Nett, Jeniel E; Hartooni, Nairi; Mui, Michael C; Andes, David R; Nobile, Clarissa J; Johnson, Alexander D

    2015-06-01

    Candida albicans biofilms are composed of highly adherent and densely arranged cells with properties distinct from those of free-floating (planktonic) cells. These biofilms are a significant medical problem because they commonly form on implanted medical devices, are drug resistant and are difficult to remove. C. albicans biofilms are not static structures; rather they are dynamic and develop over time. Here we characterize gene expression in biofilms during their development, and by comparing them to multiple planktonic reference states, we identify patterns of gene expression relevant to biofilm formation. In particular, we document time-dependent changes in genes involved in adhesion and metabolism, both of which are at the core of biofilm development. Additionally, we identify three new regulators of biofilm formation, Flo8, Gal4, and Rfx2, which play distinct roles during biofilm development over time. Flo8 is required for biofilm formation at all time points, and Gal4 and Rfx2 are needed for proper biofilm formation at intermediate time points.

  1. "PCR- Detection of Candida albicans in Blood Using a New Primer Pair to Diagnosis of Systemic Candidiasis"

    Directory of Open Access Journals (Sweden)

    SH Mirhendi

    2003-07-01

    Full Text Available The opportunistic pathogen C.albicans is able to cause disseminated infections in immunocompromised patients. Microbiological methods for the diagnosis of invasive candidiasis have many problems including low sensitivity, requirement to invasive clinical sampling such as biopsies or multiple blood cultures and need to expertise laboratory stuff. Since PCR has proven to be a powerful tool in the early diagnosis of several infectious diseases, we applied this approach as a rapid and sensitive method in detection of C.albicans cells in blood samples, for establishment a clinically useful method in diagnosing systemic candidiasis. DNA were extracted from blood samples seeded by serially diluted C.albicans cells, by omitting WBC and RBC followed by enzymatic breaking of fungal cell wall and phenol – chlorophorm extraction and alcohol precipitation of DNA. A new primer pair was designed for PCR-amplification of a part of ribosomal RNA gene. The primer set was able to amplify all medically important Candida species. When PCR was performed for detection of purified DNA, the sensitivity of the method was about 1 picogram fungal DNA, whereas the sensitivity for detection of C.albicans blastospores inoculated in blood was as few as 10 cell per 0.1 ml of blood. This method could be sensitive and useful for early and rapid diagnosis of systemic Candida infections and to simultaneous detection and speciation of Candida species by PCR-RFLP method.

  2. Species distribution & antifungal susceptibility pattern of oropharyngeal Candida isolates from human immunodeficiency virus infected individuals

    Directory of Open Access Journals (Sweden)

    Partha Pratim Das

    2016-01-01

    Results: From the 59 culture positive HIV seropositive cases, 61 Candida isolates were recovered; Candidaalbicans (n=47, 77.0%, C. dubliniensis (n=9, 14.7%, C. parapsilosis (n=2, 3.2%, C. glabrata (n=2, 3.2%, and C. famata (n=1, 1.6%. Candida colonization in HIV-seropositive individuals was significantly higher than that of HIV-seronegative (control group. Antifungal susceptibility testing revealed (n=6, 9.3% C. albicans isolates resistant to voriconazole and fluconazole by disk-diffusion method whereas no resistance was seen by Fungitest method. Interpretation & conclusions: C. albicans was the commonest Candida species infecting or colonizing HIV seropositive individuals. Oropharyngeal Candida isolates had high level susceptibility to all the major antifungals commonly in use. Increased level of immunosuppression in HIV-seropositives and drug resistance of non-albicans Candida species makes identification and susceptibility testing of Candida species necessary in different geographical areas of the country.

  3. Development of a high-throughput Candida albicans biofilm chip.

    Directory of Open Access Journals (Sweden)

    Anand Srinivasan

    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.

  4. In-vitro Inhibition of Biofilm Formation in Candida albicans and Candida tropicalis by Heat Stable Compounds in Culture Filtrate of Aspergillus flavus

    OpenAIRE

    Bhattacharyya, Sayan; Gupta, Prashant; Banerjee, Gopa; Jain, Amita; Singh, Mastan

    2013-01-01

    Background: Invasive candidiasis, caused mostly by Candida albicans and C. tropicalis is one of the most common causes of bloodstream infection with a substantial attributable mortality. This disease is associated with formation of structured, multilayered microbial communities known as biofilms over indwelling devices. Treatment is rendered difficult owing to factors like poor drug penetration through biofilms and high cost of the available antifungal drugs. Hence there is imminent need of d...

  5. Imbalanced Macrophage and Dendritic Cell Activations in Response to Candida albicans in a Murine Model of Diabetes Mellitus.

    Science.gov (United States)

    Venturini, James; Fraga-Silva, Thais Fernanda Campos; Marchetti, Camila Martins; Mimura, Luiza Ayumi Nishiyama; Conti, Bruno José; Golim, Márjorie de Assis; Mendes, Rinaldo Poncio; de Arruda, Maria Sueli Parreira

    2016-07-01

    Bloodstream infections caused by Candida species are responsible for high morbidity and mortality, and diabetes mellitus (DM) is an important underlying disease in candidemia episodes. Although DM patients show an enhanced proinflammatory profile, they are highly susceptible to mycobacterial and mycotic infections. Attempting to understand this paradox, we investigated if imbalanced macrophage and dendritic cell (DC) activations could be associated to high incidence and/or severity of Candida albicans infection in the hypoinsulinemia-hyperglycemia (HH) milieu. HH alloxan-induced mice were infected with C. albicans and peritoneal aderent phagocytes were co-cultured with or without lipopolyssaccharide or heat-killed C. albicans, and the production of cytotoxic metabolites, cytokines, and chemokines was evaluated. We also evaluated the surface expression of MHC-II and CD86 in splenic DCs. Our findings showed that both uninfected and C. albicans-infected HH mice showed less production of CCL2 and reduced expression of CD86 by peritoneal phagocytes and splenic DCs, respectively.

  6. Imbalanced Macrophage and Dendritic Cell Activations in Response to Candida albicans in a Murine Model of Diabetes Mellitus.

    Science.gov (United States)

    Venturini, James; Fraga-Silva, Thais Fernanda Campos; Marchetti, Camila Martins; Mimura, Luiza Ayumi Nishiyama; Conti, Bruno José; Golim, Márjorie de Assis; Mendes, Rinaldo Poncio; de Arruda, Maria Sueli Parreira

    2016-07-01

    Bloodstream infections caused by Candida species are responsible for high morbidity and mortality, and diabetes mellitus (DM) is an important underlying disease in candidemia episodes. Although DM patients show an enhanced proinflammatory profile, they are highly susceptible to mycobacterial and mycotic infections. Attempting to understand this paradox, we investigated if imbalanced macrophage and dendritic cell (DC) activations could be associated to high incidence and/or severity of Candida albicans infection in the hypoinsulinemia-hyperglycemia (HH) milieu. HH alloxan-induced mice were infected with C. albicans and peritoneal aderent phagocytes were co-cultured with or without lipopolyssaccharide or heat-killed C. albicans, and the production of cytotoxic metabolites, cytokines, and chemokines was evaluated. We also evaluated the surface expression of MHC-II and CD86 in splenic DCs. Our findings showed that both uninfected and C. albicans-infected HH mice showed less production of CCL2 and reduced expression of CD86 by peritoneal phagocytes and splenic DCs, respectively. PMID:27105208

  7. Comparison of the in vitro activity of echinocandins against Candida albicans, Candida dubliniensis, and Candida africana by time-kill curves.

    Science.gov (United States)

    Gil-Alonso, Sandra; Jauregizar, Nerea; Cantón, Emilia; Eraso, Elena; Quindós, Guillermo

    2015-05-01

    Candida albicans remains the most common fungal pathogen. This species is closely related to 2 phenotypically similar cryptic species, Candida dubliniensis and Candida africana. This study aims to compare the antifungal activities of echinocandins against 7 C. albicans, 5 C. dubliniensis, and 2 C. africana strains by time-kill methodology. MIC values were similar for the 3 species; however, differences in killing activity were observed among species, isolates, and echinocandins. Echinocandins produced weak killing activity against the 3 species. In all drugs, the fungicidal endpoint (99.9% mortality) was reached at ≤31 h with ≥0.5 μg/mL for anidulafungin in 4 C. albicans and 1 C. dubliniensis, for caspofungin in 1 C. albicans and 2 C. dubliniensis, and for micafungin in 4 C. albicans and 1 C. dubliniensis. None of echinocandins showed lethality against C. africana. Identification of these new cryptic species and time-kill studies would be recommendable when echinocandin treatment fails.

  8. Neonatal malnutrition programs the oxidant function of macrophages in response to Candida albicans.

    Science.gov (United States)

    Costa, Thacianna Barreto Da; Morais, Natália Gomes De; Pedrosa, Amanda Lúcia F; De Albuquerque, Suênia Da Cunha G; De Castro, Maria Carolina A B; Pereira, Valéria Rêgo A; Cavalcanti, Milena De Paiva; De Castro, Célia Maria M B

    2016-06-01

    Experimental maternal nutrition restriction models are used to investigate short or long-term consequences of nutritional deficiency on puppies' growth. By assuming that the immune function is directly related to host's nutritional status, the current study aims to investigate the effects of neonatal malnutrition on oxidative stress and on the cell death of the alveolar macrophage after in vitro infection by Candida albicans. Wistar rats were suckled by mothers fed on diets containing 17% protein (Nourished group) or 8% protein (Malnourished group) in the current assay. Both groups received the standard diet used in the vivarium until adulthood, after weaning. The results showed that the offspring from mothers fed on low-protein diet presented lower body weight from 5 days of life on. Their low weight remained until adulthood when it was compared to that of rats in the nourished group. Superoxide and nitric oxide production was lower in malnourished animals and it was accompanied by low inducible nitric oxide synthase gene expression levels in systems in which the alveolar macrophages were challenged by immunogenic stimulus. No significant differences were observed in comparisons performed between the nourished and malnourished groups in any of the analyzed cell viability (apoptosis/necrosis) parameters. The fungal inoculum-stimulated system induced higher oxidative stress and cell death by necrosis. The current study demonstrated that dietary restriction during lactation alters the oxidant function of alveolar macrophages in puppies; It happens from the gene transcription step to the release of mediators, thus compromising the host's defenses against Candida albicans. It raises the possibility that Candida albicans may cease to be a commensal fungus to become a pathogen in offspring that have suffered nutritional deficiency during critical developmental periods, due to impaired immune responses. PMID:27001703

  9. In Vitro Effect of Local Anesthetics on Candida albicans Germ Tube Formation

    Directory of Open Access Journals (Sweden)

    Acácio Rodrigues

    1994-01-01

    Full Text Available Objective: This study was planned to clarify the in vitro effect of lidocaine and bupivacaine on germ tube formation by Candida albicans isolates from cases of clinical vaginal candidiasis.

  10. In Vitro Study on the Adhesion and Colonization of Candida Albicans on Metal and Acrylic Piercings

    Directory of Open Access Journals (Sweden)

    Stamenov N.

    2016-03-01

    Full Text Available Oral/perioral piercing may provide an ideal environment for adhesion and colonization of microorganisms. The aim of this study is to perform an “in vitro” research on the capabilities of adhesion of Candida albicans on oral piercings made of plastic and metal. Acrylic and metal piercings were incubated with Candida albicans and then were observed using scanning electron microscopy under different magnifications. A lot of irregularities and roughness were observed on the surface of the plastic piercing unlike the surface of the metal one, which is not so rough. Nevertheless, the number of Candida albicans colonies was considerably larger on the scanned metal surface in comparison to the plastic surface. In vitro the metal surface of the piercing creates better environment for the adhesion and colonization of microorganisms than the acrylic. This could be attributed to the electrostatic forces that most likely attract Candida albicans to the metal piercing in the early stages of biofilm formation.

  11. Quercetin sensitizes fluconazole-resistant candida albicans to induce apoptotic cell death by modulating quorum sensing.

    Science.gov (United States)

    Singh, B N; Upreti, D K; Singh, B R; Pandey, G; Verma, S; Roy, S; Naqvi, A H; Rawat, A K S

    2015-04-01

    Quorum sensing (QS) regulates group behaviors of Candida albicans such as biofilm, hyphal growth, and virulence factors. The sesquiterpene alcohol farnesol, a QS molecule produced by C. albicans, is known to regulate the expression of virulence weapons of this fungus. Fluconazole (FCZ) is a broad-spectrum antifungal drug that is used for the treatment of C. albicans infections. While FCZ can be cytotoxic at high concentrations, our results show that at much lower concentrations, quercetin (QC), a dietary flavonoid isolated from an edible lichen (Usnea longissima), can be implemented as a sensitizing agent for FCZ-resistant C. albicans NBC099, enhancing the efficacy of FCZ. QC enhanced FCZ-mediated cell killing of NBC099 and also induced cell death. These experiments indicated that the combined application of both drugs was FCZ dose dependent rather than QC dose dependent. In addition, we found that QC strongly suppressed the production of virulence weapons-biofilm formation, hyphal development, phospholipase, proteinase, esterase, and hemolytic activity. Treatment with QC also increased FCZ-mediated cell death in NBC099 biofilms. Interestingly, we also found that QC enhances the anticandidal activity of FCZ by inducing apoptotic cell death. We have also established that this sensitization is reliant on the farnesol response generated by QC. Molecular docking studies also support this conclusion and suggest that QC can form hydrogen bonds with Gln969, Thr1105, Ser1108, Arg1109, Asn1110, and Gly1061 in the ATP binding pocket of adenylate cyclase. Thus, this QS-mediated combined sensitizer (QC)-anticandidal agent (FCZ) strategy may be a novel way to enhance the efficacy of FCZ-based therapy of C. albicans infections. PMID:25645848

  12. Lipopeptides from Bacillus subtilis AC7 inhibit adhesion and biofilm formation of Candida albicans on silicone.

    Science.gov (United States)

    Ceresa, Chiara; Rinaldi, Maurizio; Chiono, Valeria; Carmagnola, Irene; Allegrone, Gianna; Fracchia, Letizia

    2016-10-01

    Candida albicans is the major fungus that colonises medical implants, causing device-associated infections with high mortality. Antagonistic bacterial products with interesting biological properties, such as biosurfactants, have recently been considered for biofilm prevention. This study investigated the activity of lipopeptide biosurfactant produced by Bacillus subtilis AC7 (AC7 BS) against adhesion and biofilm formation of C. albicans on medical-grade silicone elastomeric disks (SEDs). Chemical analysis, stability, surface activities of AC7 BS crude extract and physicochemical characterisation of the coated silicone disk surfaces were also carried out. AC7 BS showed a good reduction of water surface tension, low critical micelle concentration, good emulsification activity, thermal resistance and pH stability. Co-incubation with 2 mg ml(-1) AC7 BS significantly reduced adhesion and biofilm formation of three C. albicans strains on SEDs in a range of 67-69 % and of 56-57 %, respectively. On pre-coated SEDs, fungal adhesion and biofilm formation were reduced by 57-62 % and 46-47 %, respectively. Additionally, AC7 BS did not inhibit viability of C. albicans strains in both planktonic and sessile form. Chemical analysis of the crude extract revealed the presence of two families of lipopeptides, principally surfactin and a lower percentage of fengycin. The evaluation of surface wettability indicated that AC7 BS coating of SEDs surface was successful although uneven. AC7 BS significantly prohibits the initial deposition of C. albicans and slows biofilm growth, suggesting a potential role of biosurfactant coatings for preventing fungal infection associated with silicone medical devices. PMID:27444239

  13. 白色假丝酵母菌感染的临床分布与药敏及生物膜类型分析%Clinical distribution and drug susceptibility and biological membrane type of Candida albicans infection

    Institute of Scientific and Technical Information of China (English)

    商安全; 吴健; 潘红超; 王微微; 刘晓明; 魏军

    2016-01-01

    目的:探讨白色假丝酵母菌感染的临床分布与药敏率以及产膜能力,为临床合理使用抗真菌药物提供科学依据。方法收集2013年1月-2015年8月住院患者标本分离出7612株真菌,真菌分离培养按《全国临床检验操作规程》进行,采用法国生物梅里埃公司全自动微生物VIT EK‐2 Compact分析仪鉴定到种,体外药敏试验采用纸片K‐B法,采用WHONET 5.6软件进行统计分析,通过结晶紫染色法对白色假丝酵母菌进行生物膜定量分析。结果分离的真菌中白色假丝酵母菌1366株,占17.9%;白色假丝酵母菌主要分离自呼吸科389株及急诊科241株,分别占28.5%及17.6%;白色假丝酵母菌的标本来源主要以痰液最多,其次为尿液及分泌物,分别占68.3%、10.5%及5.8%;白色假丝酵母菌对两性霉素B、伏立康唑、氟康唑、氟胞嘧啶、伊曲康唑的敏感率分别为100.0%、100.0%、99.9%、99.8%、98.0%;标准菌株SC5314为强产生物膜,临床分离的1366株白色假丝酵母菌中弱产生物膜325株、中等产生物膜243株、强产生物膜798株。结论白色假丝酵母菌对两性霉素B、伏立康唑、氟康唑、氟胞嘧啶、伊曲康唑依然保持较高的敏感性,白色假丝酵母菌的临床分布不同,临床治疗应合理选择抗真菌药物,同时加强对真菌耐药性的监测有助于减少耐药菌株的产生,也推动了生物膜产生能力与白色假丝酵母菌的耐药机理及致病性之间关系的进一步研究。%OBJECTIVE To comparatively analyze the clinical distribution ,drug susceptibility and capacity of bio‐logical membrane production of Candida albicans infection ,so as to provide a scientific basis for antifungal agents use in a rational way in clinic .METHODS A total of 7612 strains of fungi were isolated and collected from the pa‐tients'samples in the hospital from Jan .2013

  14. Genetic susceptibility to Candida infections.

    Science.gov (United States)

    Smeekens, Sanne P; van de Veerdonk, Frank L; Kullberg, Bart Jan; Netea, Mihai G

    2013-06-01

    Candida spp. are medically important fungi causing severe mucosal and life-threatening invasive infections, especially in immunocompromised hosts. However, not all individuals at risk develop Candida infections, and it is believed that genetic variation plays an important role in host susceptibility. On the one hand, severe fungal infections are associated with monogenic primary immunodeficiencies such as defects in STAT1, STAT3 or CARD9, recently discovered as novel clinical entities. On the other hand, more common polymorphisms in genes of the immune system have also been associated with fungal infections such as recurrent vulvovaginal candidiasis and candidemia. The discovery of the genetic susceptibility to Candida infections can lead to a better understanding of the pathogenesis of the disease, as well as to the design of novel immunotherapeutic strategies. This review is part of the review series on host-pathogen interactions. See more reviews from this series. PMID:23629947

  15. Ultrastructural and biochemical studies of two dynamically expressed cell surface determinants on Candida albicans.

    OpenAIRE

    Brawner, D L; Cutler, J E

    1986-01-01

    Variability in the expression of two different cell surface carbohydrate determinants was examined with two agglutinating immunoglobulin M monoclonal antibodies (H9 and C6) and immunoelectron microscopy during growth of three strains of Candida albicans. A single strain of Candida parapsilosis did not express either antigen at any time during growth. Antigens were detected on the surface of C. albicans by agglutination tests with either H9 or C6 over a 48-h growth period. The difference in sp...

  16. Biofilm formation is a risk factor for mortality in patients with Candida albicans bloodstream infection—Scotland, 2012–2013

    Science.gov (United States)

    Rajendran, R.; Sherry, L.; Nile, C.J.; Sherriff, A.; Johnson, E.M.; Hanson, M.F.; Williams, C.; Munro, C.A.; Jones, B.J.; Ramage, G.

    2016-01-01

    Bloodstream infections caused by Candida species remain a significant cause of morbidity and mortality in hospitalized patients. Biofilm formation by Candida species is an important virulence factor for disease pathogenesis. A prospective analysis of patients with Candida bloodstream infection (n = 217) in Scotland (2012–2013) was performed to assess the risk factors associated with patient mortality, in particular the impact of biofilm formation. Candida bloodstream isolates (n = 280) and clinical records for 157 patients were collected through 11 different health boards across Scotland. Biofilm formation by clinical isolates was assessed in vitro with standard biomass assays. The role of biofilm phenotype on treatment efficacy was also evaluated in vitro by treating preformed biofilms with fixed concentrations of different classes of antifungal. Available mortality data for 134 patients showed that the 30-day candidaemia case mortality rate was 41%, with predisposing factors including patient age and catheter removal. Multivariate Cox regression survival analysis for 42 patients showed a significantly higher mortality rate for Candida albicans infection than for Candida glabrata infection. Biofilm-forming ability was significantly associated with C. albicans mortality (34 patients). Finally, in vitro antifungal sensitivity testing showed that low biofilm formers and high biofilm formers were differentially affected by azoles and echinocandins, but not by polyenes. This study provides further evidence that the biofilm phenotype represents a significant clinical entity, and that isolates with this phenotype differentially respond to antifungal therapy in vitro. Collectively, these findings show that greater clinical understanding is required with respect to Candida biofilm infections, and the implications of isolate heterogeneity. PMID:26432192

  17. 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.

  18. PENGHAMBATAN CAJUPUTS CANDY TERHADAP VIABILITAS KHAMIR Candida albicans SECARA IN VITRO [Inhibition of Cajuputs Candy Toward the Viability of Candida albicans by using In Vitro Assay

    OpenAIRE

    C. Hanny Wijaya 2); A. Fieki Rachmatillah1); Bachtiar, Boy M.

    2014-01-01

    The utilization of cajuput essential oil as a flavor in candy may produce a physiological active added value. Some compounds of cajuput plant (Melaleuca cajuputi L) have been reported for their anti-microbial activities. Candida albicans is a normal commensal organism in human mouth. However, it may become virulent and responsible for oral diseases known as oral candidiasis. This study aimed to determine the effect of cajuput and peppermint oil in cajuputs candy in inhibiting the C. albicans ...

  19. 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.

  20. Is Candida albicans a trigger in the onset of coeliac disease?

    NARCIS (Netherlands)

    Nieuwenhuizen, W.F.; Pieters, R.H.H.; Knippels, L.M.J.; Jansen, M.C.J.F.; Koppelman, S.J.

    2003-01-01

    Coeliac disease is a T-cell-mediated autoimmune disease of the small intestine that is induced by ingestion of gluten proteins from wheat, barley, or rye. We postulate that Candida albicans is a trigger in the onset of coeliac disease. The virulence factor of C albicans - hyphal wall protein 1 (HWP1

  1. Cell Wall Polysaccharides of Candida albicans Induce Mast Cell Degranulation in the Gut

    OpenAIRE

    Sakurai, Atsuko; Yamaguchi, Natsu; Sonoyama, Kei

    2012-01-01

    We investigated Candida albicans-induced mast cell degranulation in vitro and in vivo. Cell wall fraction but not culture supernatant and cell membrane fraction prepared from hyphally grown C. albicans induced β-hexosaminidase release in RBL-2H3 cells. Cell wall mannan and soluble β-glucan fractions also induced β-hexosaminidase release. Histological examination of mouse forestomach showed that C. albicans gut colonization induces mast cell degranulation. However, intragastric administration ...

  2. Sap6, a secreted aspartyl proteinase, participates in maintenance the cell surface integrity of Candida albicans

    OpenAIRE

    Buu, Leh-Miauh; Chen, Yee-Chun

    2013-01-01

    Background The polymorphic species Candida albicans is the major cause of candidiasis in humans. The secreted aspartyl proteinases (Saps) of C. albicans, encoded by a family of 10 SAP genes, have been investigated as the virulent factors during candidiasis. However, the biological functions of most Sap proteins are still uncertain. In this study, we applied co-culture system of C. albicans and THP-1 human monocytes to explore the pathogenic roles and biological functions of Sap proteinases. R...

  3. Funktionelle Analyse einer Familie von Oligopeptidtransportern des humanpathogenen Hefepilzes Candida albicans

    OpenAIRE

    Reuß, Oliver Rainer

    2006-01-01

    Der Hefepilz Candida albicans ist Teil der natürlichen Mikroflora auf den Schleimhäuten des Verdauungs- und Urogenitaltrakts der meisten gesunden Menschen. Allerdings kann C. albicans vor allem in immunsupprimierten Patienten auch schwerwiegende Infektionen verursachen. Diese reichen von oberflächlichen Mykosen bis hin zu lebensbedrohlichen systemischen Infektionen. C. albicans besitzt eine Reihe von Eigenschaften, die es diesem opportunistisch humanpathogenen Pilz ermöglichen unterschiedlich...

  4. 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.

  5. Antifungal Activity of Bee Venom and Sweet Bee Venom against Clinically Isolated Candida albicans

    OpenAIRE

    Seung-Bae Lee

    2016-01-01

    Objectives: The purpose of this study was to investigate the antifungal effect of bee venom (BV) and sweet bee venom (SBV) against Candida albicans (C. albicans) clinical isolates. Methods: In this study, BV and SBV were examined for antifungal activities against the Korean Collection for Type Cultures (KCTC) strain and 10 clinical isolates of C. albicans. The disk diffusion method was used to measure the antifungal activity and minimum inhibitory concentration (MIC) assays were performed by ...

  6. Anti-Candida albicans activity of Pichia anomala as determined by a growth rate reduction assay.

    OpenAIRE

    Sawant, A D; Abdelal, A T; Ahearn, D G

    1988-01-01

    Killer toxin activity of Pichia anomala WC65 appeared fungicidal for P. bimundalis WC38 and fungistatic for Candida albicans RC1. Inhibitory activity against sensitive C. albicans showed a linear relationship between toxin concentrations and the inverse of the reduced growth rates. The plot of toxin concentrations against growth rates was hyperbolic, as is characteristic of saturation kinetics. Sensitivity of C. albicans to the toxin decreased with increased cell age. The measurement of growt...

  7. Self-Regulation of Candida albicans Population Size during GI Colonization

    OpenAIRE

    White, Sarah Jane; Rosenbach, Ari; Lephart, Paul; Nguyen, Diem; Benjamin, Alana; Tzipori, Saul; Whiteway, Malcolm; Mecsas, Joan; Kumamoto, Carol A.

    2007-01-01

    Interactions between colonizing commensal microorganisms and their hosts play important roles in health and disease. The opportunistic fungal pathogen Candida albicans is a common component of human intestinal flora. To gain insight into C. albicans colonization, genes expressed by fungi grown within a host were studied. The EFH1 gene, encoding a putative transcription factor, was highly expressed during growth of C. albicans in the intestinal tract. Counterintuitively, an efh1 null mutant ex...

  8. Successful Granulocyte Colony-stimulating Factor Treatment of Relapsing Candida albicans Meningoencephalitis Caused by CARD9 Deficiency.

    Science.gov (United States)

    Celmeli, Fatih; Oztoprak, Nefise; Turkkahraman, Doga; Seyman, Derya; Mutlu, Esvet; Frede, Natalie; Köksoy, Sadi; Grimbacher, Bodo

    2016-04-01

    Caspase-associated recruitment domain-9 (CARD9) deficiency is an autosomal-recessive primary immunodeficiency with genetic defects in Th17 immunity marked by susceptibility to recurrent and invasive Candida infections. We present a case of relapsing Candida albicans meningoencephalitis over 1-year period despite appropriate antifungal therapy. We detected a homozygous p.Q295X mutation in CARD9 as well as a defective interleukin-17 and interferon gamma synthesis in Enzyme-Linked ImmunoSpot tests. We achieved complete clinical remission, and improvement of interleukin-17 secretion with subcutaneous granulocyte colony-stimulating factor) treatment. PMID:26658378

  9. Role of autophagy genetic variants for the risk of Candida infections

    NARCIS (Netherlands)

    Rosentul, D.C.; Plantinga, T.S.; Farcas, M.; Oosting, M.; Hamza, O.J.M.; Scott, W.K.; Alexander, B.D.; Yang, J.C.; Laird, G.M.; Joosten, L.A.B.; Meer, J.W.M. van der; Perfect, J.R.; Kullberg, B.J.; Ven, A.J.A.M. van der; Johnson, M.D.; Netea, M.G.

    2014-01-01

    Candida albicans can cause candidemia in neutropenic and critically ill patients and oropharyngeal candidiasis in human immunodeficiency virus (HIV)-positive patients with low CD4(+) counts. Because all patients at risk do not develop Candida infections, it is possible that a patient's genetic backg

  10. A piglet model for studying Candida albicans colonization of the human oro-gastrointestinal tract.

    Science.gov (United States)

    Hoeflinger, Jennifer L; Coleman, David A; Oh, Soon-Hwan; Miller, Michael J; Hoyer, Lois L

    2014-08-01

    Pigs from a variety of sources were surveyed for oro-gastrointestinal (oro-GIT) carriage of Candida albicans. Candida albicans-positive animals were readily located, but we also identified C. albicans-free pigs. We hypothesized that pigs could be stably colonized with a C. albicans strain of choice, simply by feeding yeast cells. Piglets were farrowed routinely and remained with the sow for 4 days to acquire a normal microbiota. Piglets were then placed in an artificial rearing environment and fed sow milk replacer. Piglets were inoculated orally with one of three different C. albicans strains. Piglets were weighed daily, and culture swabs were collected to detect C. albicans orally, rectally and in the piglet's environment. Stable C. albicans colonization over the course of the study did not affect piglet growth. Necropsy revealed mucosally associated C. albicans throughout the oro-GIT with the highest abundance in the esophagus. Uninoculated control piglets remained C. albicans-negative. These data establish the piglet as a model to study C. albicans colonization of the human oro-GIT. Similarities between oro-GIT colonization in humans and pigs, as well as the ease of working with the piglet model, suggest its adaptability for use among investigators interested in understanding C. albicans-host commensal interactions.

  11. 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.

  12. A novel role for the NLRC4 inflammasome in mucosal defenses against the fungal pathogen Candida albicans.

    Directory of Open Access Journals (Sweden)

    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.

  13. Risk factors, antibiotics exposure and outcomes of patients with Candida albicans and non-Candida albicans bloodstream infection%白念珠菌与非白念珠菌血流感染危险因素、抗菌药物应用及预后比较

    Institute of Scientific and Technical Information of China (English)

    王昊; 吴大玮; 韩辉; 岳金凤; 张帆; 单梯超; 郭海鹏; 尹梅; 刘乃政

    2014-01-01

    Objective To investigate the risk factors,antibiotics exposure and outcomes in hospitalized patients with Candida albicans (C.albicans) bloodstream infection (CABSI) and non-C.albicans bloodstream infection (NABSI).Methods The clinical data of 56 patients with CABSI and 76 patients with NABSI from January 2009 to June 2010 were collected and reviewed.Two-sample t-test and chi-square test were used for statistical analysis.Risk factors of NABSI were evaluated by Logistic regression analysis.Results Compared to CABSI group,more patients in NABSI group received surgery operations (38.2% vs 21.4% ; x2 =4.214,P<0.05),central venous catheter (CVC) placement (63.2% vs 41.1% ; x2 =6.328,P<0.05),and less patients received mechanical ventilation (26.3% vs 44.6% ; x2 =4.820,P<0.05).And more patients with NABSI received antifungal agents (40.8% vs 21.4%; x2 =5.503,P<0.05) and nitroimidazoles agents (23.7% vs 8.9%; x2 =4.879,P<0.05) and less patients received β-lactam/β-lactamase inhibitors (34.2 % vs 51.8 % ; x2 =4.098,P<0.05).In multivariate analysis,independent risk factors of NABSI were prior nitroimidazoles agents (OR=1.276,95% CI:1.132-9.708),antifungal agents therapy (OR =1.902,95% CI:1.250-4.685) and CVC placement (OR =3.437,95%CI..1.269-17.323).Overall 30-day-mortality in patients with CABSI was higher than patients with NABSI (50.0% vs31.6%; x2=4.583,P<0.05).Conclusions Prior treatment of antifungal agents,nitroimidazoles agents and CVC placement are associated with the development of NABSI.Compared with NABSI,CABSI is associated with worse prognosis and should be treated with caution.%目的 探讨白念珠菌血流感染(CABSI)和非白念珠菌血流感染(NABSI)患者的危险因素、抗菌药物应用和预后的差异.方法 回顾性分析2009年1月至2010年6月收治的56例CABSI和76例NASBI患者的临床资料,组间比较采用独立样本t检验和x 2检验,相关性分析采

  14. [Molecular epidemiologic surveillance and antifungal agent sensitivity of Candida albicans isolated from anesthesia intensive care units].

    Science.gov (United States)

    Gülay, Zeynep; Ergon, Cem; Ozkütük, Aydan; Yücesoy, Mine; Biçmen, Meral

    2002-01-01

    Patients in intensive care units (ICU) are at risk of nosocomial infections. The incidence of nosocomial fungal infections has increased in parallel with the increase of nosocomial infections. Candida albicans is the most frequent pathogenic species among the fungi. The aim of this study was to make an epidemiological surveillance of C. albicans urine isolates which were isolated from patients who were hospitalized in ICU between June 2000 and October 2001 by antifungal susceptibility testing and Randomly Amplified Polymorphic DNA (RAPD) analysis. For this purpose, 38 C. albicans which were isolated from 29 patients were investigated for amphotericin B and fluconazole susceptibility with the microdilution method. The range of minimal inhibitory concentration (MIC) of amphotericin B was between 0.25-1 microgram/ml and MIC50 value was 0.5 microgram/ml and none of the isolates had high (MIC > 1 microgram/ml) MIC values. The MIC values for fluconazole varied between 0.25-16 micrograms/ml and MIC50 value was 1 microgram/ml. While none of the isolates was resistant to fluconazole, two isolates were detected as dose dependent susceptible. RAPD analysis was performed with two different primers in order to investigate clonal relationship, and 22 patterns were detected with one of the primers and 24 patterns were detected with the other. In conclusion, it is thought that the origin of the C. albicans urine isolates were mostly endogenous but exogenous spread might also be considered as isolates that were clonally related were isolated from different patients at the same time interval.

  15. [Phospholipase, proteinase and hemolytic activities of Candida albicans isolates obtained from clinical specimens].

    Science.gov (United States)

    Yenişehirli, Gülgün; Bulut, Yunus; Tunçoglu, Ebru

    2010-01-01

    This study was aimed to determine the phospholipase, proteinase and hemolytic activities of Candida albicans strains isolated from clinical specimens. A total of 147 C. albicans strains isolated from blood (n = 29), respiratory specimens (n = 44), urine (n = 52), pus (n = 17) and stool (n = 5) were included in the study. Proteinase and phospholipase activities were determined in 81% and 76% of C. albicans isolates, respectively. All C. albicans isolates revealed beta-hemolytic activity on Sabouraud dextrose agar supplemented with 7% fresh sheep blood and 3% glucose. Phospholipase and proteinase positivity were highest among the respiratory isolates. Proteinase activity of respiratory (93%) and blood (83%) isolates were statistically significantly higher than that of urine (77%; p = 0.032), pus (65%; p = 0.007) and stool isolates (60%; p = 0.026). While phospholipase activity showed statistically significant difference between respiratory (84%) and pus (53%) isolates (p = 0.014), no statistically significant difference was determined for blood (79%), urine (75%) and stool (80%) isolates (p > 0.05). Two blood isolates with 4+ proteinase activity and 3 urine isolates with 3+ proteinase activity were phospholipase negative. One urine isolate with 4+ phospholipase activity and 4 with 3+ phospholipase activity were proteinase negative. Phospholipase and proteinase negative 1 isolate from stool and 1 isolate from pus were found to have 4+ hemolytic activity. In conclusion, besides proteinase and phospholipase enzyme activities, hemolytic activity may play an important role for the C.albicans infections. The pathogenetic role of these virulence factors should be evaluated by further clinical studies.

  16. A novel antifungal is active against Candida albicans biofilms and inhibits mutagenic acetaldehyde production in vitro.

    Directory of Open Access Journals (Sweden)

    Mikko T Nieminen

    Full Text Available The ability of C. albicans to form biofilms is a major virulence factor and a challenge for management. This is evident in biofilm-associated chronic oral-oesophageal candidosis, which has been shown to be potentially carcinogenic in vivo. We have previously shown that most Candida spp. can produce significant levels of mutagenic acetaldehyde (ACH. ACH is also an important mediator of candidal biofilm formation. We have also reported that D,L-2-hydroxyisocaproic acid (HICA significantly inhibits planktonic growth of C. albicans. The aim of the present study was to investigate the effect of HICA on C. albicans biofilm formation and ACH production in vitro. Inhibition of biofilm formation by HICA, analogous control compounds or caspofungin was measured using XTT to measure biofilm metabolic activity and PicoGreen as a marker of biomass. Biofilms were visualised by scanning electron microscopy (SEM. ACH levels were measured by gas chromatography. Transcriptional changes in the genes involved in ACH metabolism were measured using RT-qPCR. The mean metabolic activity and biomass of all pre-grown (4, 24, 48 h biofilms were significantly reduced after exposure to HICA (p40 µM of ACH were detected in 24 and 48 h biofilms at both pHs. Interestingly, no ACH production was detected from D-glucose in the presence of HICA at acidic pH (p<0.05. Expression of genes responsible for ACH catabolism was up-regulated by HICA but down-regulated by caspofungin. SEM showed aberrant hyphae and collapsed hyphal structures during incubation with HICA at acidic pH. We conclude that HICA has potential as an antifungal agent with ability to inhibit C. albicans cell growth and biofilm formation. HICA also significantly reduces the mutagenic potential of C. albicans biofilms, which may be important when treating bacterial-fungal biofilm infections.

  17. Retrospective analysis of Candida albicans infections in hospitalized patients%住院患者白色假丝酵母菌感染的临床回顾性分析

    Institute of Scientific and Technical Information of China (English)

    曹俊敏; 曹毅; 杨雪静; 季聪华

    2012-01-01

    目的 探讨医院内白色假丝酵母菌感染的临床和流行病学特点,为减少白色假丝酵母菌感染以及相关白色假丝酵母菌的研究提供依据.方法 回顾性分析2010年9月-2011年9月住院患者白色假丝酵母菌的检出情况、标本来源、科室分布、疾病种类、医疗干预措施以及抗菌药物的使用等,并对定植组和感染确诊组的相关易感因素进行x2检验和logistic回归分析.结果 检出白色假丝酵母菌感染166例,其中101例白色假丝酵母菌确诊患者患有多种基础疾病,以肺部感染、高血压、恶性肿瘤常见;白血病在两组间差异有统计学意义,白血病患者中感染确诊组明显多于定植组;两组在静脉留置、留置导尿管、免疫抑制剂、肠外营养、放化疗、腹腔穿刺间差异有统计学意义;头孢菌素类、喹诺酮类、碳青霉烯类抗菌药物在两组间的使用差异有统计学意义;检出以>70岁的老年患者为主,中位年龄76岁;主要分离自痰液标本占64.5%;患者主要来自血液科、ICU、肿瘤科等.结论 感染确诊组与定植组相比,白血病、免疫抑制剂、肠外营养、放化疗、静脉置管、头孢菌素类、碳青霉烯类、喹诺酮类抗菌药物的使用是感染确诊组主要的危险因素;警惕白色假丝酵母菌感染的相关危险因素,对临床防治该菌感染具有重要意义.%OBJECTIVE To describe the clinical epidemiological characteristics of Candida albicans infections in hospitalized patients so as to provide bases for the reduction of C. albicans infections and related study on C. albicans. METHODS The isolation status,specimens sources, department distribution, the types of diseases, medical interventions and the use of antibiotics were retrospectively analyzed for the hospitalized patients form Sep 2010 to Sep 2011; x2 test and logistic regression analysis were performed for the relevant susceptible factors of the

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

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    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.

  19. 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.

  20. Contact-free inactivation of Candida albicans biofilms by cold atmospheric air plasma.

    Science.gov (United States)

    Maisch, Tim; Shimizu, Tetsuji; Isbary, Georg; Heinlin, Julia; Karrer, Sigrid; Klämpfl, Tobias G; Li, Yang-Fang; Morfill, Gregor; Zimmermann, Julia L

    2012-06-01

    Candida albicans is one of the main species able to form a biofilm on almost any surface, causing both skin and superficial mucosal infections. The worldwide increase in antifungal resistance has led to a decrease in the efficacy of standard therapies, prolonging treatment time and increasing health care costs. Therefore, the aim of this work was to demonstrate the applicability of atmospheric plasma at room temperature for inactivating C. albicans growing in biofilms without thermally damaging heat-sensitive materials. This so-called cold atmospheric plasma is produced by applying high voltage to accelerate electrons, which ionize the surrounding air, leading to the production of charged particles, reactive species, and photons. A newly developed plasma device was used, which exhibits a large plasma-generating surface area of 9 by 13 cm (117 cm(2)). Different time points were selected to achieve an optimum inactivation efficacy range of ≥3 log(10) to 5 log(10) reduction in CFU per milliliter, and the results were compared with those of 70% ethanol. The results obtained show that contact-free antifungal inactivation of Candida biofilms by cold atmospheric plasma is a promising tool for disinfection of surfaces (and items) in both health care settings and the food industry, where ethanol disinfection should be avoided.

  1. 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.

  2. The fungus Candida albicans tolerates ambiguity at multiple codons

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    João Salvador Simões

    2016-03-01

    Full Text Available The ascomycete Candida albicans is a normal resident of the gastrointestinal tract of humans and other warm-blooded animals. It occurs in a broad range of body sites and has high capacity to survive and proliferate in adverse environments with drastic changes in oxygen, carbon dioxide, pH, osmolarity, nutrients and temperature. Its biology is unique due to flexible reassignment of the leucine CUG codon to serine and synthesis of statistical proteins. Under standard growth conditions 3% of leucine and 97% of serine are incorporated at CUG sites on a proteome wide scale, but leucine incorporation fluctuates in response to environmental stressors and can be artificially increased up to 98%. In order to determine whether such flexibility also exists at other codons, we have constructed several serine tRNAs that decode various non-cognate codons. Expression of these tRNAs had minor effects on fitness, but growth of the mistranslating strains at different temperatures, in medium with different pH and nutrients composition was often enhanced relatively to the wild type (WT strain, supporting our previous data on adaptive roles of CUG ambiguity in variable growth conditions. Parallel evolution of the recombinant strains (100 generations followed by full genome resequencing identified various strain specific single nucleotide polymorphisms (SNP and one SNP in the deneddylase (JAB1 gene in all strains. Since JAB1 is a subunit of the COP9 signalosome complex, which interacts with cullin (Cdc53p to mediate degradation of a variety of cellular proteins, our data suggest that neddylation plays a key role in tolerance and adaptation to codon ambiguity in C. albicans.

  3. Susceptibility of Candida albicans to new synthetic sulfone derivatives.

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    Staniszewska, Monika; Bondaryk, Małgorzata; Ochal, Zbigniew

    2015-02-01

    The influence of halogenated methyl sulfones, i.e. bromodichloromethyl-4-chloro-3-nitrophenyl sulfone (named halogenated methyl sulfone 1), dichloromethyl-4-chloro-3-nitrophenyl sulfone (halogenated methyl sulfone 2), and chlorodibromomethyl-4-hydrazino-3-nitrophenyl sulfone (halogenated methyl sulfone 3), on cell growth inhibition, aspartic protease gene (SAP4-6) expression, adhesion to epithelium, and filamentation was investigated. Antifungal susceptibility of the halogenated methyl sulfones was determined with the M27-A3 protocol in the range of 16-0.0313 µg/mL. Adherence to Caco-2 cells was performed in 24-well plates; relative quantification was normalized against ACT1 in cells after 18 h of growth in YEPD and on Caco-2 cells. SAP4-6 expression was analyzed using RT-PCR. Structure-activity relationship studies suggested that halogenated methyl sulfone 1 containing bromodichloromethyl or dichloromethyl function at C-4 (halogenated methyl sulfone 2) of the phenyl ring showed the best activity (100% cell inhibition at 0.5 µg/mL), while hydrazine at C-1 (halogenated methyl sulfone 3) reduced the sulfone potential (100% = 4 µg/mL). SAP4-6 were up- or down-regulated depending on the strains' genetic background and the substitutions on the phenyl ring. Halogenated methyl sulfone 2 repressed germination and affected adherence to epithelium (P ≤ 0.05). The tested halogenated methyl sulfones interfered with the adhesion of Candida albicans cells to the epithelial tissues, without affecting their viability after 90 min of incubation. The mode of action of the halogenated methyl sulfones was attributed to the reduced virulence of C. albicans. SAP5 and SAP6 contribute to halogenated methyl sulfones resistance. Thus, halogenated methyl sulfones can inhibit biofilm formation due to their interference with adherence and with the yeast-to-hyphae transition.

  4. Bruton's Tyrosine Kinase (BTK and Vav1 contribute to Dectin1-dependent phagocytosis of Candida albicans in macrophages.

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    Karin Strijbis

    Full Text Available Phagocytosis of the opportunistic fungal pathogen Candida albicans by cells of the innate immune system is vital to prevent infection. Dectin-1 is the major phagocytic receptor involved in anti-fungal immunity. We identify two new interacting proteins of Dectin-1 in macrophages, Bruton's Tyrosine Kinase (BTK and Vav1. BTK and Vav1 are recruited to phagocytic cups containing C. albicans yeasts or hyphae but are absent from mature phagosomes. BTK and Vav1 localize to cuff regions surrounding the hyphae, while Dectin-1 lines the full length of the phagosome. BTK and Vav1 colocalize with the lipid PI(3,4,5P3 and F-actin at the phagocytic cup, but not with diacylglycerol (DAG which marks more mature phagosomal membranes. Using a selective BTK inhibitor, we show that BTK contributes to DAG synthesis at the phagocytic cup and the subsequent recruitment of PKCε. BTK- or Vav1-deficient peritoneal macrophages display a defect in both zymosan and C. albicans phagocytosis. Bone marrow-derived macrophages that lack BTK or Vav1 show reduced uptake of C. albicans, comparable to Dectin1-deficient cells. BTK- or Vav1-deficient mice are more susceptible to systemic C. albicans infection than wild type mice. This work identifies an important role for BTK and Vav1 in immune responses against C. albicans.

  5. Clonal Strain Persistence of Candida albicans Isolates from Chronic Mucocutaneous Candidiasis Patients.

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    Alexander J Moorhouse

    Full Text Available Chronic mucocutaneous candidiasis (CMC is a primary immunodeficiency disorder characterised by susceptibility to chronic Candida and fungal dermatophyte infections of the skin, nails and mucous membranes. Molecular epidemiology studies of CMC infection are limited in number and scope and it is not clear whether single or multiple strains inducing CMC persist stably or are exchanged and replaced. We subjected 42 C. albicans individual single colony isolates from 6 unrelated CMC patients to multilocus sequence typing (MLST. Multiple colonies were typed from swabs taken from multiple body sites across multiple time points over a 17-month period. Among isolates from each individual patient, our data show clonal and persistent diploid sequence types (DSTs that were stable over time, identical between multiple infection sites and exhibit azole resistant phenotypes. No shared origin or common source of infection was identified among isolates from these patients. Additionally, we performed C. albicans MLST SNP genotype frequency analysis to identify signatures of past loss of heterozygosity (LOH events among persistent and azole resistant isolates retrieved from patients with autoimmune disorders including CMC.

  6. Proteomic profiling of serologic response to Candida albicans during host-commensal and host-pathogen interactions.

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    Pitarch, Aida; Nombela, César; Gil, Concha

    2009-01-01

    Candida albicans is a commensal inhabitant of the normal human microflora that can become pathogenic and invade almost all body sites and organs in response to both host-mediated and fungus-mediated mechanisms. Serologic responses to C. albicans that underlie its dichotomist relationship with the host (host-commensal and host-pathogen interactions) display a high degree of heterogeneity, resulting in distinct serum anti-Candida antibody signatures (molecular fingerprints of anti-Candida antibodies in serum) that can be used to discriminate commensal colonization from invasive disease. We describe the typical proteomic strategy to globally and integratively profile these host antibody responses and determine serum antibody signatures. This approach is based on the combination of classic immunoproteomics or serologic proteome analysis (two-dimensional electrophoresis followed by quantitative Western blotting and mass spectrometry) with data mining procedures. This global proteomic stratagem is a useful tool not only for obtaining an overview of different anti-Candida antibodies that are being elicited during the host-fungus interaction and, consequently, of the complex C. albicans immunome (the subset of the C. albicans proteome targeted by the immune system), but also for evaluating how this pathogen organism interacts with its host to trigger infection. In contrast with genomics and transcriptomics, this proteomic technology has the potential to detect antigenicity associated with posttranslational modification, subcellular localization, and other functional aspects that can be relevant in the host immune response. Furthermore, this strategy to define molecular fingerprints of serum anti-Candida antibodies may hopefully bring to light potential candidates for diagnosis, prognosis, risk stratification, clinical follow-up, therapeutic monitoring, and/or immunotherapy of candidiasis, especially of its life-threatening systemic forms. PMID:19089396

  7. The role of candida albicans in the pathogenesis of psoriasis vulgaris: a systematic literature review

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    Sona Sepahi

    2016-07-01

    Full Text Available Introduction: Psoriasis is a chronic, inflammatory skin disease that is related to many genetic, and environmental factors, as well as infectious pathogens. Findings suggest that the Candida species, particularly Candida albicans, may play a role in the pathogenesis of psoriasis vulgaris. In this study, we aimed to systematically review the possible association between C. albicans and the prevalence of psoriasis. Methods: A systematic search of existing literature was performed in the PubMed, Scopus and Google Scholar databases and the Google search engine using the following search strategy ((Candida albicans OR C. albicans OR Candida AND (psoriasis vulgaris OR plaque psoriasis OR psoriasis to find relevant articles that described a possible positive or negative association between C. albicans and the incidence or progression of psoriasis. The search was not limited to articles that were published within a specific time period; however, only those written in the English language were included in the review.Result: Of the 499 articles in total that were identified during the initial database search, 491 were excluded from the review because they failed to meet the inclusion/exclusion criteria. The total number of people involved in the selected studies, including both patients and healthy controls, was 1260. The analysis of the results of the included documents showed that the colonization of C. albicans is more prevalent in biological specimens taken from psoriatic patients.Conclusion: Studies show that C. albicans, opportunistic yeast, like diploid fungus, may be involved in the pathogenesis of psoriasis.

  8. Morphological and physiological changes induced by contact-dependent interaction between Candida albicans and Fusobacterium nucleatum

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    Bor, Batbileg; Cen, Lujia; Agnello, Melissa; Shi, Wenyuan; He, Xuesong

    2016-01-01

    Candida albicans and Fusobacterium nucleatum are well-studied oral commensal microbes with pathogenic potential that are involved in various oral polymicrobial infectious diseases. Recently, we demonstrated that F. nucleatum ATCC 23726 coaggregates with C. albicans SN152, a process mainly mediated by fusobacterial membrane protein RadD and Candida cell wall protein Flo9. The aim of this study was to investigate the potential biological impact of this inter-kingdom interaction. We found that F. nucleatum ATCC 23726 inhibits growth and hyphal morphogenesis of C. albicans SN152 in a contact-dependent manner. Further analysis revealed that the inhibition of Candida hyphal morphogenesis is mediated via RadD and Flo9 protein pair. Using a murine macrophage cell line, we showed that the F. nucleatum-induced inhibition of Candida hyphal morphogenesis promotes C. albicans survival and negatively impacts the macrophage-killing capability of C. albicans. Furthermore, the yeast form of C. albicans repressed F. nucleatum-induced MCP-1 and TNFα production in macrophages. Our study suggests that the interaction between C. albicans and F. nucleatum leads to a mutual attenuation of virulence, which may function to promote a long-term commensal lifestyle within the oral cavity. This finding has significant implications for our understanding of inter-kingdom interaction and may impact clinical treatment strategies. PMID:27295972

  9. Self-regulation of Candida albicans population size during GI colonization.

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    Sarah Jane White

    2007-12-01

    Full Text Available Interactions between colonizing commensal microorganisms and their hosts play important roles in health and disease. The opportunistic fungal pathogen Candida albicans is a common component of human intestinal flora. To gain insight into C. albicans colonization, genes expressed by fungi grown within a host were studied. The EFH1 gene, encoding a putative transcription factor, was highly expressed during growth of C. albicans in the intestinal tract. Counterintuitively, an efh1 null mutant exhibited increased colonization of the murine intestinal tract, a model of commensal colonization, whereas an EFH1 overexpressing strain exhibited reduced colonization of the intestinal tract and of the oral cavity of athymic mice, the latter situation modeling human mucosal candidiasis. When inoculated into the bloodstream of mice, both efh1 null and EFH1 overexpressing strains caused lethal infections. In contrast, other mutants are attenuated in virulence following intravenous inoculation but exhibited normal levels of intestinal colonization. Finally, although expression of several genes is dependent on transcription factor Efg1p during laboratory growth, Efg1p-independent expression of these genes was observed during growth within the murine intestinal tract. These results show that expression of EFH1 regulated the level of colonizing fungi, favoring commensalism as opposed to candidiasis. Also, different genes are required in different host niches and the pathway(s that regulates gene expression during host colonization can differ from well-characterized pathways used during laboratory growth.

  10. 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.

  11. 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.

  12. 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.

  13. In vitro antifungal and antibiofilm activities of halogenated quinoline analogues against Candida albicans and Cryptococcus neoformans.

    Science.gov (United States)

    Zuo, Ran; Garrison, Aaron T; Basak, Akash; Zhang, Peilan; Huigens, Robert W; Ding, Yousong

    2016-08-01

    With the increasing prevalence of fungal infections coupled with emerging drug resistance, there is an urgent need for new and effective antifungal agents. Here we report the antifungal activities of 19 diverse halogenated quinoline (HQ) small molecules against Candida albicans and Cryptococcus neoformans. Four HQ analogues inhibited C. albicans growth with a minimum inhibitory concentration (MIC) of 100 nM, whilst 16 analogues effectively inhibited C. neoformans at MICs of 50-780 nM. Remarkably, two HQ analogues eradicated mature C. albicans and C. neoformans biofilms [minimum biofilm eradication concentration (MBEC) = 6.25-62.5 µM]. Several active HQs were found to penetrate into fungal cells, whilst one inactive analogue was unable to, suggesting that HQs elicit their antifungal activities through an intracellular mode of action. HQs are a promising class of small molecules that may be useful in future antifungal treatments. PMID:27256584

  14. Ethno botany and antimicrobial perspective of Spices and Honey against Candida albicans

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    Kothai Nil Seshathri

    2013-04-01

    Full Text Available Aim: In spite of obsessive use of spices in every Ethiopian meal, little has been investigated on the utilization of Ethiopian spices as a cure for oral opportunistic infections. Therefore the aim was to identify spices used in Ethiopian food through ethno botanical survey and study their antifungal activity against Candida albicans. Method: Ethno botanical survey of the selected Kebeles of Jimma, Ethiopia was conducted using a semi structured questionnaire from October 2006 to November 2007. Antifungal nature of the spices and combination of spices and honey were evaluated by agar well diffusion assay from September 2008 to July 2010. Result: Ethno botanical survey indicated fourteen species of spices and honey play a major role in Ethiopian food and beverages. Single plant extract of Trachyspermum copticum showed highest activity against C. albicans. The same plant showed antagonistic effect when combined with brown and white honey. Cinamomum zeylanicum showed highest synergistic effect with both brown and white honey when compared to Allium ursenum, Cuminum cyminum, Nigella sativa, Rosemarinus officinalis and Occimum hodiense. Conclusion: Thus spices used in Ethiopian food could be a preventive as well as a cure for oral candidiasis caused by C.albicans. [J Intercult Ethnopharmacol 2013; 2(2.000: 73-80

  15. 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.

  16. In vivo inhibitory effect on the biofilm formation of Candida albicans by liverwort derived riccardin D.

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    Yan Li

    Full Text Available Riccardin D, a macrocyclic bisbibenzyl isolated from Chinese liverwort Dumortiera hirsute, has been proved to have inhibitory effect on biofilms formation of Candida albicans in in vitro study. Our present study aims to investigate the in vivo effect and mechanisms of riccardin D against C. albicans biofilms when used alone or in combination with clinical using antifungal agent fluconazole. XTT reduction assay revealed riccardin D had both prophylactic and therapeutic effect against C. albicans biofilms formation in a dose-dependent manner when using a central venous catheter related infective animal model. Scanning electron microscope and laser confocal scanning microscope showed that the morphology of biofilms was altered remarkably after riccardin D treatment, especially hypha growth inhibition. To uncover the underlying molecular mechanisms, quantitative real-time RT-PCR was performed to observe the variation of related genes. The downregulation of hypha-specific genes such as ALS1, ALS3, ECE1, EFG1, HWP1 and CDC35 following riccardin D treatment suggested riccardin D inhibited the Ras-cAMP-Efg pathway to retard the hypha formation, then leading to the defect of biofilms maturation. Moreover, riccardin D displayed an increased antifungal activity when administered in combination with fluconazole. Our study provides a potential clinical application to eliminate the biofilms of relevant pathogens.

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

    Science.gov (United States)

    Capoci, Isis Regina Grenier; Bonfim-Mendonça, Patrícia de Souza; Arita, Glaucia Sayuri; Pereira, Raphaela Regina de Araújo; Consolaro, Marcia Edilaine Lopes; Bruschi, Marcos Luciano; Negri, Melyssa; Svidzinski, Terezinha Inez Estivalet

    2015-01-01

    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. PMID:25815029

  18. 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.

  19. Novel Regulatory Mechanisms of Pathogenicity and Virulence to Combat MDR in Candida albicans

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    Saif Hameed

    2013-01-01

    Full Text Available Continuous deployment of antifungals in treating infections caused by dimorphic opportunistic pathogen Candida albicans has led to the emergence of drug resistance resulting in cross-resistance to many unrelated drugs, a phenomenon termed multidrug resistance (MDR. Despite the current understanding of major factors which contribute to MDR mechanisms, there are many lines of evidence suggesting that it is a complex interplay of multiple factors which may be contributed by still unknown mechanisms. Coincidentally with the increased usage of antifungal drugs, the number of reports for antifungal drug resistance has also increased which further highlights the need for understanding novel molecular mechanisms which can be explored to combat MDR, namely, ROS, iron, hypoxia, lipids, morphogenesis, and transcriptional and signaling networks. Considering the worrying evolution of MDR and significance of C. albicans being the most prevalent human fungal pathogen, this review summarizes these new regulatory mechanisms which could be exploited to prevent MDR development in C. albicans as established from recent studies.

  20. A subset of IL-17+ mesenchymal stem cells possesses anti-Candida albicans effect

    Institute of Scientific and Technical Information of China (English)

    Ruili Yang; Yi Liu; Peyman Kelk; Cunye Qu; Kentaro Akiyama; Chider Chen; Ikiru Atsuta

    2013-01-01

    Bone marrow mesenchymal stem cells (MSCs) comprise a heterogeneous population of postnatal progenitor cells with profound immunomodulatory properties,such as upregulation of Foxp3+ regulatory T cells (Tregs) and downregulation of Th17 cells.However,it is unknown whether different MSC subpopulations possess the same range of immunomodulatory function.Here,we show that a subset of single colony-derived MSCs producing IL-17 is different from bulk MSC population in that it cannot upregulate Tregs,downregulate Th17 cells,or ameliorate disease phenotypes in a colitis mouse model.Mechanistically,we reveal that IL-17,produced by these MSCs,activates the NFκB pathway to downregulate TGF-β production in MSCs,resulting in abolishment of MSC-based immunomodulation.Furthermore,we show that NFκB is able to directly bind to TGF-β promoter region to regulate TGF-β expression in MSCs.Moreover,these IL-17+ MSCs possess anti-Candida albicans growth effects in vitro and therapeutic effect in C.albicans-infected mice.In summary,this study shows that MSCs contain an IL-17+ subset capable of inhibiting C.albicans growth,but attenuating MSC-based immunosuppression via NFκB-mediated downregulation of TGF-β.

  1. Fungistatic activity of all-trans retinoic acid against Aspergillus fumigatus and Candida albicans

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    Campione E

    2016-04-01

    Full Text Available Elena Campione,1 Roberta Gaziano,2 Daniele Marino,2 Augusto Orlandi3 1Department of Dermatology, 2Department of Microbiology, 3Department of Anatomic Pathology, University of Rome Tor Vergata, Rome, Italy Purpose: Fungal infections are a major complication in hematologic and neoplastic patients causing severe morbidity and mortality. Aspergillus fumigatus and Candida albicans are among the most invasive opportunistic pathogens in immunocompromised patients, and classic antifungal drugs are frequently unsuccessful in these patients. Recent reports hypothesize that the antifungal efficacy of all-trans retinoic acid (ATRA is mainly related to its strong capacity to stimulate monocyte-mediated immunity, but no consideration was given to its potential direct fungistatic activity. Moreover, ATRA offers the opportunity for systemic therapy. Methods and results: We investigated the efficacy of ATRA at different concentrations for its antifungal activity against opportunistic A. fumigatus and C. albicans obtained from clinical samples according to standard protocols. A fungistatic activity of ATRA on A. fumigatus and C. albicans at 0.5–1 mM concentration was documented up to 7 days. Conclusion: This is the first evidence of a direct and strong fungistatic activity of ATRA against A. fumigatus and C. albicans. The potential adjuvant therapeutic application of ATRA might be useful in the treatment and/or prevention of systemic mycoses in immunocompromised patients. The discovery of a direct fungistatic activity, in association with its reported immunomodulatory properties, makes ATRA an excellent candidate for new combined antifungal strategies for systemic mycoses in immunocompromised and cancer patients. Keywords: all-trans retinoic acid, fungistatic activity, fungal infections

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

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    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

  3. Emergence of non-albicans Candida species and antifungal resistance in intensive care unit patients

    Institute of Scientific and Technical Information of China (English)

    Ravinder Kaur; Megh Singh Dhakad; Ritu Goyal; Rakesh Kumar

    2016-01-01

    Objective: To evaluate the epidemiology of candidiasis and the antifungal susceptibility profile of Candida species isolated from the intensive care unit (ICU) patients. Methods: The study used a qualitative descriptive design. Relevant samples depending on organ system involvement from 100 ICU patients were collected and processed. Identification and speciation of the isolates was conducted by the biochemical tests. Antifungal susceptibility testing was carried out as per CLSI-M27-A3 document. Results: Ninety Candida isolates were isolated from the different clinical samples:urine (43.3%), tracheal aspirate (31.1%), urinary catheter (12.2%), endotracheal tube (7.8%), abdominal drains (3.3%), sputum (2.2%). The incidence of candidiasis caused by non-albicans Candida (NAC) species (63.3%) was higher than Candida albicans (36.7%). The various NAC species were isolated as: Candida tropicalis (41.1%), Candida glab-rata (10%), Candida parapsilosis (6.7%), Candida krusei (3.3%) and Candida kefyr (2.2%). The overall isolation rate of Candida species from samples was 53.3%. Anti-fungal susceptibility indicated that 37.8%and 7.8%of the Candida isolates were resistant to fluconazole and amphotericin B, respectively. Conclusions: Predominance of NAC species in ICU patients along with the increasing resistance being recorded to fluconazole which has a major bearing on the morbidity and management of these patients and needs to be further worked upon.

  4. Molecular mechanisms of primary resistance to flucytosine in Candida albicans.

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    Hope, William W; Tabernero, Lydia; Denning, David W; Anderson, Michael J

    2004-11-01

    Primary resistance in Candida albicans to flucytosine (5-FC) was investigated in 25 strains by identifying and sequencing the genes FCA1, FUR1, FCY21, and FCY22, which code for cytosine deaminase, uracil phosphoribosyltransferase (UPRT), and two purine-cytosine permeases, respectively. These proteins are involved in pyrimidine salvage and 5-FC metabolism. An association between a polymorphic nucleotide and resistance to 5-FC was found within FUR1 where the substitution of cytidylate for thymidylate at nucleotide position 301 results in the replacement of arginine with cysteine at amino acid position 101 in UPRT. Isolates that are homozygous for this mutation display increased levels of resistance to 5-FC, whereas heterozygous isolates have reduced susceptibility. Three-dimensional protein modeling of UPRT suggests that the Arg101Cys mutation disturbs the quaternary structure of the enzyme, which is postulated to compromise optimal enzyme activity. A single resistant isolate, lacking the above polymorphism in FUR1, has a homozygous polymorphism in FCA1 that results in a glycine-to-aspartate substitution at position 28 in cytosine deaminase.

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

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    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.

  6. The role of pattern recognition receptors in the innate recognition of Candida albicans.

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    Zheng, Nan-Xin; Wang, Yan; Hu, Dan-Dan; Yan, Lan; Jiang, Yuan-Ying

    2015-01-01

    Candida albicans is both a commensal microorganism in healthy individuals and a major fungal pathogen causing high mortality in immunocompromised patients. Yeast-hypha morphological transition is a well known virulence trait of C. albicans. Host innate immunity to C. albicans critically requires pattern recognition receptors (PRRs). In this review, we summarize the PRRs involved in the recognition of C. albicans in epithelial cells, endothelial cells, and phagocytic cells separately. We figure out the differential recognition of yeasts and hyphae, the findings on PRR-deficient mice, and the discoveries on human PRR-related single nucleotide polymorphisms (SNPs).

  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. Neutrophil extracellular traps contain calprotectin, a cytosolic protein complex involved in host defense against Candida albicans.

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    Constantin F Urban

    2009-10-01

    Full Text Available Neutrophils are the first line of defense at the site of an infection. They encounter and kill microbes intracellularly upon phagocytosis or extracellularly by degranulation of antimicrobial proteins and the release of Neutrophil Extracellular Traps (NETs. NETs were shown to ensnare and kill microbes. However, their complete protein composition and the antimicrobial mechanism are not well understood. Using a proteomic approach, we identified 24 NET-associated proteins. Quantitative analysis of these proteins and high resolution electron microscopy showed that NETs consist of modified nucleosomes and a stringent selection of other proteins. In contrast to previous results, we found several NET proteins that are cytoplasmic in unstimulated neutrophils. We demonstrated that of those proteins, the antimicrobial heterodimer calprotectin is released in NETs as the major antifungal component. Absence of calprotectin in NETs resulted in complete loss of antifungal activity in vitro. Analysis of three different Candida albicans in vivo infection models indicated that NET formation is a hitherto unrecognized route of calprotectin release. By comparing wild-type and calprotectin-deficient animals we found that calprotectin is crucial for the clearance of infection. Taken together, the present investigations confirmed the antifungal activity of calprotectin in vitro and, moreover, demonstrated that it contributes to effective host defense against C. albicans in vivo. We showed for the first time that a proportion of calprotectin is bound to NETs in vitro and in vivo.

  9. Blocking of Candida albicans biofilm formation by cis-2-dodecenoic acid and trans-2-dodecenoic acid.

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    Zhang, Yuqian; Cai, Chen; Yang, Yuxiang; Weng, Lixing; Wang, Lianhui

    2011-11-01

    Candida is an important opportunistic human fungal pathogen. Infections caused by Candida albicans are related to the formation of a biofilm. The biofilm enhances the resistance of the C. albicans defence system, increases its resistance to antifungal drugs and induces increased drug tolerance, making clinical care more challenging. The in vitro activity of cis-2-dodecenoic acid (BDSF; a diffusible signal factor from Burkholderia cenocepacia) and trans-2-dodecenoic acid (trans-BDSF) against C. albicans growth, germ-tube germination and biofilm formation was estimated by absorbance measurements and microscopic assessments. C. albicans biofilms were prepared using a static microtitre plate model. Quantitative analysis of biofilm formation was performed using a 2,3-bis(2-methoxy-4-nitro-5-sulfo-phenyl)-2H-tetrazolium-5-carboxanilide reduction assay to evaluate the effect of different concentrations of BDSF and trans-BDSF at different stages of biofilm formation. Reductions in biofilm structure and formation were visualized by inverted microscopy. Real-time RT-PCR was employed to estimate the mRNA expression levels of the hyphae-specific genes HWP1 and ALS3. It was found that 30 µM of either BDSF or trans-BDSF reduced germ-tube formation by approximately 70 % without inhibiting yeast growth. Yeast growth was strongly repressed by the exogenous addition of 300 µM BDSF and trans-BDSF at 0 and 1 h after cell attachment, with biofilm formation being reduced by approximately 90 and 60 %, respectively. BDSF and trans-BDSF were more effective against biofilm formation than farnesol and the diffusible signal factor cis-11-methyl-2-dodecenoic acid. None of the four drugs was able to destroy pre-formed biofilms. Real-time RT-PCR analysis showed that HWP1 was downregulated by approximately 90 % and ALS3 was downregulated by 70-80 % by 60 µM BDSF and trans-BDSF, implying that BDSF and trans-BDSF block C. albicans biofilm formation by interfering with the morphological

  10. Evaluation of Urinary Tract Infections Due to Candida Species

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    Yeser Karaca Derici

    2016-02-01

    Full Text Available Aim: Although urinary tract infections often caused by bacteria, fungal etiology is detected in a significant number of infections in which Candida is the leading cause. In this study we aimed to evaluate the distribution of Candida strains isolated from urine samples in our hospital. Material and Method: Candida species were identified based on germ tube test, colony morphology on chrom agar Candida (Biomerieux, France and API ID32C AUX (Biomerieux, France commercial kit. Data were analyzed with SPSS 15.0 software for data analysis. Results: During March 2011-March 2014 a total of 109662 urine cultures were evaluated and 24364 samples revealed significant growth. Of the significant growth detected 24364 (22% samples 1096 (4.5% were defined as yeasts. The isolates most frequently detected in this study were C. albicans (50.5%, C. tropicalis (15.9%, C. glabrata (12.7%, C. parapsilosis (7.2%, C. kefyr (5.8%, C. krusei (5.5%. The highest yeast growth was observed in anesthesia intensive care unit. Discussion: In our study, the most frequently isolated species of yeast in the urine was C. albicans. Determination of Candida species and their clinical distributions in hospitals is very important in terms of giving direction to the treatment and measures to be taken.

  11. Antifungal susceptibility and molecular typing of 115 Candida albicans isolates obtained from vulvovaginal candidiasis patients in 3 Shanghai maternity hospitals.

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    Ying, Chunmei; Zhang, Hongju; Tang, Zhenhua; Chen, Huifen; Gao, Jing; Yue, Chaoyan

    2016-05-01

    In our multicenter study, we studied the distribution of Candida species in vulvovaginal candidiasis patients and investigated antifungal susceptibility profile and genotype of Candida albicans in vaginal swab. A total of 115 Candida albicans strains were detected in 135 clinical isolates. Minimum inhibitory concentration determinations showed that 83% and 81% of the 115 Candida albicans strains were susceptible to fluconazole and voriconazole. Randomly amplified polymorphic DNA analysis (RAPD) was applied to identify clonally related isolates from different patients at the local level. All tested strains were classified into genotype A (77.4%), genotype B (18.3%), and genotype C (4.3%). Genotype A was further classified into five subtypes and genotype B into two subtypes.Candida albicans was the dominant pathogen of vulvovaginal candidiasis, the majority belonging to genotype A in this study. Exposure to azoles is a risk factor for the emergence of azole resistance among Candida albicans isolated from VVC patients.

  12. Immunoproteomic Analysis of Antibody Responses to Extracellular Proteins of Candida albicans Revealing the Importance of Glycosylation for Antigen Recognition.

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    Luo, Ting; Krüger, Thomas; Knüpfer, Uwe; Kasper, Lydia; Wielsch, Natalie; Hube, Bernhard; Kortgen, Andreas; Bauer, Michael; Giamarellos-Bourboulis, Evangelos J; Dimopoulos, George; Brakhage, Axel A; Kniemeyer, Olaf

    2016-08-01

    During infection, the human pathogenic fungus Candida albicans undergoes a yeast-to-hypha transition, secretes numerous proteins for invasion of host tissues, and modulates the host's immune response. Little is known about the interplay of C. albicans secreted proteins and the host adaptive immune system. Here, we applied a combined 2D gel- and LC-MS/MS-based approach for the characterization of C. albicans extracellular proteins during the yeast-to-hypha transition, which led to a comprehensive C. albicans secretome map. The serological responses to C. albicans extracellular proteins were investigated by a 2D-immunoblotting approach combined with MS for protein identification. On the basis of the screening of sera from candidemia and three groups of noncandidemia patients, a core set of 19 immunodominant antibodies against secreted proteins of C. albicans was identified, seven of which represent potential diagnostic markers for candidemia (Xog1, Lip4, Asc1, Met6, Tsa1, Tpi1, and Prx1). Intriguingly, some secreted, strongly glycosylated protein antigens showed high cross-reactivity with sera from noncandidemia control groups. Enzymatic deglycosylation of proteins secreted from hyphae significantly impaired sera antibody recognition. Furthermore, deglycosylation of the recombinantly produced, secreted aspartyl protease Sap6 confirmed a significant contribution of glycan epitopes to the recognition of Sap6 by antibodies in patient's sera. PMID:27386892

  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.

  14. A transmission electron microscopy study of the diversity of Candida albicans cells induced by Euphorbia hirta L.leaf extract in vitro

    Institute of Scientific and Technical Information of China (English)

    Abu; Arra; Basma; Zakaria; Zuraini; Sreenivasan; Sasidharan

    2011-01-01

    Objective:To determine the major changes in the microstructure of Candida albicans(C. albicans) after treatment with Euphorbia hirta(E.hirta) L.leaf extract.Methods:Transmission electron microscopy was used to study the ultrastructural changes caused by E.hirta extract on C. albicans cells al various exposure time.Results:It was found that the main abnormalities were the alterations in morphology,lysis and complete collapse of the yeast cells after 36 h of exposure to the extract.Whereas the control cultures showed a typical morphology of Candida with a uniform central density,typically structured nucleus,and a cytoplasm with several elements of endomembrane system and enveloped by a regular,intact cell wall.Conclusions:The significant antifungal activity shown by this methanol extract of E.hirta L.suggests its potential against infections caused by C.albicans.The extract may be developed as an anticandidal agent.

  15. A transmission electron microscopy study of the diversity of Candida albicans cells induced by Euphorbia hirta L. leaf extract in vitro

    Institute of Scientific and Technical Information of China (English)

    Abu Arra Basma; Zakaria Zuraini; Sreenivasan Sasidharan

    2011-01-01

    Objective: To determine the major changes in the microstructure of Candida albicans (C. albicans) after treatment with Euphorbia hirta (E. hirta) L. leaf extract. Methods: Transmission electron microscopy was used to study the ultrastructural changes caused by E. hirta extract on C.albicans cells at various exposure time. Results: It was found that the main abnormalities were the alterations in morphology, lysis and complete collapse of the yeast cells after 36 h of exposure to the extract. Whereas the control cultures showed a typical morphology of Candida with a uniform central density, typically structured nucleus, and a cytoplasm with several elements of endomembrane system and enveloped by a regular, intact cell wall. Conclusions: The significant antifungal activity shown by this methanol extract of E. hirta L. suggests its potential against infections caused by C. albicans. The extract may be developed as an anticandidal agent.

  16. Person-to-person transfer of Candida albicans in the spacecraft environment

    Science.gov (United States)

    Pierson, D. L.; Mehta, S. K.; Magee, B. B.; Mishra, S. K.

    1995-01-01

    We assessed the exchange of Candida albicans among crew members during 10 Space Shuttle missions. Throat, nasal, urine and faecal specimens were collected from 61 crew members twice before and once after space flights ranging from 7 to 10 days in duration; crews consisted of groups of five, six or seven men and women. Candida albicans was isolated at least once from 20 of the 61 subjects (33%). Candida strains were identified by restriction-fragment length polymorphism (RFLP) after digestion by the endonucleases EcoRI and HinfI; further discrimination was gained by Southern blot hybridization with the C. albicans repeat fragment 27A. Eighteen of the 20 Candida-positive crew members carried different strains of C. albicans in the specimens collected. Possible transfer of C. albicans between members of the same crew was demonstrated only once in the 10 missions studied. We conclude that the transfer of C. albicans among crew members during Space Shuttle flights is less frequent than had been predicted from earlier reports.

  17. Pseudomonas aeruginosa lipopolysaccharide inhibits Candida albicans hyphae formation and alters gene expression during biofilm development.

    Science.gov (United States)

    Bandara, H M H N; K Cheung, B P; Watt, R M; Jin, L J; Samaranayake, L P

    2013-02-01

    Elucidation of bacterial and fungal interactions in multispecies biofilms will have major impacts on understanding the pathophysiology of infections. The objectives of this study were to (i) evaluate the effect of Pseudomonas aeruginosa lipopolysaccharide (LPS) on Candida albicans hyphal development and transcriptional regulation, (ii) investigate protein expression during biofilm formation, and (iii) propose likely molecular mechanisms for these interactions. The effect of LPS on C. albicans biofilms was assessed by XTT-reduction and growth curve assays, light microscopy, scanning electron microscopy (SEM), and confocal laser scanning microscopy (CLSM). Changes in candidal hypha-specific genes (HSGs) and transcription factor EFG1 expression were assessed by real-time polymerase chain reaction and two-dimensional gel electrophoresis, respectively. Proteome changes were examined by mass spectrometry. Both metabolic activities and growth rates of LPS-treated C. albicans biofilms were significantly lower (P yeasts in test biofilms compared with the controls. SEM and CLSM further confirmed these data. Significantly upregulated HSGs (at 48 h) and EFG1 (up to 48 h) were noted in the test biofilms (P < 0.05) but cAMP levels remained unaffected. Proteomic analysis showed suppression of candidal septicolysin-like protein, potential reductase-flavodoxin fragment, serine hydroxymethyltransferase, hypothetical proteins Cao19.10301(ATP7), CaO19.4716(GDH1), CaO19.11135(PGK1), CaO19.9877(HNT1) by P. aeruginosa LPS. Our data imply that bacterial LPS inhibit C. albicans biofilm formation and hyphal development. The P. aeruginosa LPS likely target glycolysis-associated mechanisms during candidal filamentation. PMID:23194472

  18. Candida albicans Inhibits Pseudomonas aeruginosa Virulence through Suppression of Pyochelin and Pyoverdine Biosynthesis.

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    Eduardo Lopez-Medina

    2015-08-01

    Full Text Available Bacterial-fungal interactions have important physiologic and medical ramifications, but the mechanisms of these interactions are poorly understood. The gut is host to trillions of microorganisms, and bacterial-fungal interactions are likely to be important. Using a neutropenic mouse model of microbial gastrointestinal colonization and dissemination, we show that the fungus Candida albicans inhibits the virulence of the bacterium Pseudomonas aeruginosa by inhibiting P. aeruginosa pyochelin and pyoverdine gene expression, which plays a critical role in iron acquisition and virulence. Accordingly, deletion of both P. aeruginosa pyochelin and pyoverdine genes attenuates P. aeruginosa virulence. Heat-killed C. albicans has no effect on P. aeruginosa, whereas C. albicans secreted proteins directly suppress P. aeruginosa pyoverdine and pyochelin expression and inhibit P. aeruginosa virulence in mice. Interestingly, suppression or deletion of pyochelin and pyoverdine genes has no effect on P. aeruginosa's ability to colonize the GI tract but does decrease P. aeruginosa's cytotoxic effect on cultured colonocytes. Finally, oral iron supplementation restores P. aeruginosa virulence in P. aeruginosa and C. albicans colonized mice. Together, our findings provide insight into how a bacterial-fungal interaction can modulate bacterial virulence in the intestine. Previously described bacterial-fungal antagonistic interactions have focused on growth inhibition or colonization inhibition/modulation, yet here we describe a novel observation of fungal-inhibition of bacterial effectors critical for virulence but not important for colonization. These findings validate the use of a mammalian model system to explore the complexities of polymicrobial, polykingdom infections in order to identify new therapeutic targets for preventing microbial disease.

  19. Convergent Regulation of Candida albicans Aft2 and Czf1 in Invasive and Opaque Filamentation.

    Science.gov (United States)

    Xu, Ning; Dong, Yi-Jie; Yu, Qi-Lin; Zhang, Bing; Zhang, Meng; Jia, Chang; Chen, Yu-Lu; Zhang, Biao; Xing, Lai-Jun; Li, Ming-Chun

    2015-09-01

    Candida albicans is the most common fungal pathogen of mucosal infections and invasive diseases in immuno-compromised humans. The abilities of yeast-hyphal growth and white-opaque switching affect C. albicans physiology and virulence. Here, we showed that C. albicans Aft2 regulator was required for embedded filamentous growth and opaque cell-type formation. Under low-temperature matrix embedded conditions, Aft2 functioned downstream of Czf1-mediated pathway and was required for invasive filamentation. Moreover, deletion of AFT2 significantly reduced opaque cell-type formation under N-acetylglucosamine (GlcNAc) inducing conditions. Ectopic expression of CZF1 slightly increased the white-opaque switching frequency in the aft2Δ/Δ mutant, but did not completely restore to wild-type levels, suggesting that Czf1 at least partially bypassed the essential requirement for Aft2 in response to opaque-inducing cues. In addition, multiple environmental cues altered AFT2 mRNA and protein levels, such as low temperature, physical environment and GlcNAc. Although the absence of Czf1 or Efg1 also increased the expression level of AFT2 gene, deletion of CZF1 remarkably reduced the stability of Aft2 protein. Furthermore, C. albicans Aft2 physically interacted with Czf1 under all tested conditions, whereas the interaction between Aft2 and Efg1 was barely detectable under embedded conditions, supporting the hypothesis that Aft2, together with Czf1, contributed to activate filamentous growth by antagonizing Efg1-mediated repression under matrix-embedded conditions.

  20. The first report of treatment of liver abscess due to Candida albicans with intra-abscess and intravenous administration of liposomal amphotericin B (Amphotec)

    Institute of Scientific and Technical Information of China (English)

    LIAO Wan-qing; YAO Zhi-rong; WEN Hai; XU Hong; YANG Song-lin; LIU Xing-hua; TAN Wei-ping

    2005-01-01

    Increasing reports on application and safety of liposomal amphotericin B (Amphotec) in the treatment of deep fungal infections have been described recently. This is the first report that a case of liver abscess due to Candida albicans was completely cured with intra-abscess and intravenous administration of liposomal amphotericin B without recurrence in three-year follow-up period.

  1. Efficient surface functionalization of wound dressings by a phytoactive nanocoating refractory to Candida albicans biofilm development.

    Science.gov (United States)

    Anghel, Ion; Holban, Alina Maria; Andronescu, Ecaterina; Grumezescu, Alexandru Mihai; Chifiriuc, Mariana Carmen

    2013-12-01

    The present study reports the fabrication and characterization of a novel nanostructured phyto-bioactive coated rayon/polyester wound dressing (WD) surface refractory to Candida albicans adhesion, colonization and biofilm formation, based on functionalized magnetite nanoparticles and Anethum graveolens (AG) and Salvia officinalis (SO) essential oils (EOs). TEM, XRD, TGA, FT-IR were used for the characterization of the fabricated nanobiocoated WDs. Using magnetic nanoparticles for the stabilization and controlled release of EOs, the activity of natural volatile compounds is significantly enhanced and their effect is stable during time. For this reason the nanobiocoated surfaces exhibited a longer term anti-biofilm effect, maintained for at least 72 h. Besides their excellent anti- adherence properties, the proposed solutions exhibit the advantage of using vegetal natural compounds, which are less toxic and easily biodegradable in comparison with synthetic antifungal drugs, representing thus promising approaches for the development of successful ways to control and prevent fungal biofilms associated infections. PMID:24706124

  2. Disruption of homocitrate synthase genes in Candida albicans affects growth but not virulence.

    Science.gov (United States)

    Kur, Krzysztof; Gabriel, Iwona; Morschhäuser, Joachim; Barchiesi, Francesco; Spreghini, Elisabetta; Milewski, Sławomir

    2010-12-01

    Two genes, LYS21 and LYS22, encoding isoforms of homocitrate synthase, an enzyme catalysing the first committed step in the lysine biosynthetic pathway, were disrupted in Candida albicans using the SAT1 flipper strategy. The double null lys21Δ/lys22Δ mutant lacked homocitrate synthase activity and exhibited lysine auxotrophy in minimal media that could be fully rescued by the addition of 0.5-0.6 mM L: -lysine. On the other hand, its virulence in vivo in the model of disseminated murine candidiasis appeared identical to that of the mother, wild-type strain. These findings strongly question a possibility of exploitation of homocitrate synthase and possibly also other enzymes of the lysine biosynthetic pathway as targets in chemotherapy of disseminated fungal infections.

  3. Molecular Docking Evaluation of Imidazole Analogues as Potent Candida albicans 14α-Demethylase Inhibitors.

    Science.gov (United States)

    Rani, Nidhi; Kumar, Praveen; Singh, Randhir; Sharma, Ajay

    2015-01-01

    Candida albicans is one of the most important causes of life-threating fungal infections. Lanosterol 14α-demethylase (Cytochrome P450DM) is the target enzyme of azole antifungal agents. The study involved selection and modeling of the target enzyme followed by refinement of the model using molecular dynamic simulation. The modeled structure of enzyme was validated using Ramachandran plot and Sequence determination technique. A series of chlorosubstituted imidazole analogues were evaluated for Cytochrome P450 inhibitory activity using molecular docking studies. The imidazole analogues were prepared using Chem sketch and molecular docking was performed using Molergo Virtual Docker program. The docking study indicated that all the imidazole analogues (AN1-AN45) and standard drugs i.e., Ketoconazole, Clotrimazole and Miconazole have interaction with protein residue of 14α-demethylase, Heme cofactor and the water molecules present in the active site. PMID:26081558

  4. Candida albicans commensalism and pathogenicity are intertwined traits directed by a tightly knit transcriptional regulatory circuit.

    Directory of Open Access Journals (Sweden)

    J Christian Pérez

    Full Text Available Systemic, life-threatening infections in humans are often caused by bacterial or fungal species that normally inhabit a different locale in our body, particularly mucosal surfaces. A hallmark of these opportunistic pathogens, therefore, is their ability to thrive in disparate niches within the host. In this work, we investigate the transcriptional circuitry and gene repertoire that enable the human opportunistic fungal pathogen Candida albicans to proliferate in two different niches. By screening a library of transcription regulator deletion strains in mouse models of intestinal colonization and systemic infection, we identified eight transcription regulators that play roles in at least one of these models. Using genome-wide chromatin immunoprecipitation, we uncovered a network comprising ∼800 target genes and a tightly knit transcriptional regulatory circuit at its core. The network is enriched with genes upregulated in C. albicans cells growing in the host. Our findings indicate that many aspects of commensalism and pathogenicity are intertwined and that the ability of this microorganism to colonize multiple niches relies on a large, integrated circuit.

  5. Biochemical analysis and application of molecular display technology on Candida albicans for diagnosing and preventing candidiasis.

    Science.gov (United States)

    Shibasaki, Seiji; Aoki, Wataru; Ueda, Mitsuyoshi

    2013-01-01

    Medical facilities and advances in therapeutics have improved world over in recent times. Concomitant with this, the human population has been growing steadily. However, emerging infectious diseases such as severe acute respiratory syndrome (SARS) and AIDS, as well as re-emerging infectious diseases such as Japanese encephalitis and dengue fever, have been spreading in recent times. Three major infectious diseases, namely AIDS, malaria, and tuberculosis, are killing around 8 million people in the world annually. Although drugs effective against these infectious diseases are available at present, drastic therapeutics have not been developed yet. In addition, vaccines against these diseases often cannot prevent infections, because pathogenic viruses or bacteria evade the immune system of the host. Many diseases and emerging infections of pathogenic bacteria cannot be controlled by conventional pharmaceutics. These pathogens secrete regulatory factors. When the produced regulatory factor attains a certain level, an active factor is then produced by the pathogen to destroy the host. Considering these phenomena, we thought investigating characteristic regulatory or active factors will pave the way for developing novel vaccines or diagnostic drugs. Therefore, candidiasis was selected as a model, and application of the secretory protease of Candida albicans was examined for the development of novel drugs. Screening of novel candidates of antigens of C. albicans and vaccine development are also underway. In this paper, our strategy of platform technology against various infectious diseases are introduced.

  6. Candida albicans Pathogenesis: Fitting within the Host-Microbe Damage Response Framework.

    Science.gov (United States)

    Jabra-Rizk, Mary Ann; Kong, Eric F; Tsui, Christina; Nguyen, M Hong; Clancy, Cornelius J; Fidel, Paul L; Noverr, Mairi

    2016-10-01

    Historically, the nature and extent of host damage by a microbe were considered highly dependent on virulence attributes of the microbe. However, it has become clear that disease is a complex outcome which can arise because of pathogen-mediated damage, host-mediated damage, or both, with active participation from the host microbiota. This awareness led to the formulation of the damage response framework (DRF), a revolutionary concept that defined microbial virulence as a function of host immunity. The DRF outlines six classifications of host damage outcomes based on the microbe and the strength of the immune response. In this review, we revisit this concept from the perspective of Candida albicans, a microbial pathogen uniquely adapted to its human host. This fungus commonly colonizes various anatomical sites without causing notable damage. However, depending on environmental conditions, a diverse array of diseases may occur, ranging from mucosal to invasive systemic infections resulting in microbe-mediated and/or host-mediated damage. Remarkably, C. albicans infections can fit into all six DRF classifications, depending on the anatomical site and associated host immune response. Here, we highlight some of these diverse and site-specific diseases and how they fit the DRF classifications, and we describe the animal models available to uncover pathogenic mechanisms and related host immune responses. PMID:27430274

  7. Single-cell force spectroscopy of the medically important Staphylococcus epidermidis-Candida albicans interaction

    Science.gov (United States)

    Beaussart, Audrey; Herman, Philippe; El-Kirat-Chatel, Sofiane; Lipke, Peter N.; Kucharíková, Soňa; van Dijck, Patrick; Dufrêne, Yves F.

    2013-10-01

    Despite the clinical importance of bacterial-fungal interactions, their molecular details are poorly understood. A hallmark of such medically important interspecies associations is the interaction between the two nosocomial pathogens Staphylococcus aureus and Candida albicans, which can lead to mixed biofilm-associated infections with enhanced antibiotic resistance. Here, we use single-cell force spectroscopy (SCFS) to quantify the forces engaged in bacterial-fungal co-adhesion, focusing on the poorly investigated S. epidermidis-C. albicans interaction. Force curves recorded between single bacterial and fungal germ tubes showed large adhesion forces (~5 nN) with extended rupture lengths (up to 500 nm). By contrast, bacteria poorly adhered to yeast cells, emphasizing the important role of the yeast-to-hyphae transition in mediating adhesion to bacterial cells. Analysis of mutant strains altered in cell wall composition allowed us to distinguish the main fungal components involved in adhesion, i.e. Als proteins and O-mannosylations. We suggest that the measured co-adhesion forces are involved in the formation of mixed biofilms, thus possibly as well in promoting polymicrobial infections. In the future, we anticipate that this SCFS platform will be used in nanomedicine to decipher the molecular mechanisms of a wide variety of pathogen-pathogen interactions and may help in designing novel anti-adhesion agents.

  8. Biochemical analysis and application of molecular display technology on Candida albicans for diagnosing and preventing candidiasis.

    Science.gov (United States)

    Shibasaki, Seiji; Aoki, Wataru; Ueda, Mitsuyoshi

    2013-01-01

    Medical facilities and advances in therapeutics have improved world over in recent times. Concomitant with this, the human population has been growing steadily. However, emerging infectious diseases such as severe acute respiratory syndrome (SARS) and AIDS, as well as re-emerging infectious diseases such as Japanese encephalitis and dengue fever, have been spreading in recent times. Three major infectious diseases, namely AIDS, malaria, and tuberculosis, are killing around 8 million people in the world annually. Although drugs effective against these infectious diseases are available at present, drastic therapeutics have not been developed yet. In addition, vaccines against these diseases often cannot prevent infections, because pathogenic viruses or bacteria evade the immune system of the host. Many diseases and emerging infections of pathogenic bacteria cannot be controlled by conventional pharmaceutics. These pathogens secrete regulatory factors. When the produced regulatory factor attains a certain level, an active factor is then produced by the pathogen to destroy the host. Considering these phenomena, we thought investigating characteristic regulatory or active factors will pave the way for developing novel vaccines or diagnostic drugs. Therefore, candidiasis was selected as a model, and application of the secretory protease of Candida albicans was examined for the development of novel drugs. Screening of novel candidates of antigens of C. albicans and vaccine development are also underway. In this paper, our strategy of platform technology against various infectious diseases are introduced. PMID:24189555

  9. Phage displaying epitope of Candida albicans HSP90 and serodiagnosis

    Institute of Scientific and Technical Information of China (English)

    杨琼; 王丽; 卢大宁; 邢沈阳; 尹东; 朱筱娟

    2004-01-01

    @@ Recently, the frequent use of immunosuppressants and chemotherapeutic drugs for cancers has caused an increase in the frequency of life-threatening systemic candidiasis.1 Studies by Matthews et al2 indicated HSP90 fragments are major targets for the immune system in infection due to C. albicans, and anti-epitope LKVIRK of HSP90 antibody is a serological marker for diagnosis of invasive candidiasis. Cloning and sequencing HSP90 antigen revealed that the linear epitope LKVIRK, localized near the C-terminus of the 47 kDa protein which circulates in the sera of patients with invasive candidiasis, as a heat-stable breakdown product of large more heat-labile antigen HSP90.2 In this study, epitope LKVIRK was displayed on the surface of phage fd to develop a new serological test for systemic candidiasis.

  10. An Unusual Cause of Renal and Perirenal Abscesses: Candida albicans

    Directory of Open Access Journals (Sweden)

    Serhan PİŞKİNPAŞA

    2014-01-01

    Full Text Available A 42-year-old female with history of surgery due to urolithiasis was admitted to hospital with complaints of fever, left fl ank pain and vomiting. She was found to have acute kidney injury due to urinary tract infection. Abdominal computed tomography revealed right atrophic kidney and left renal and perirenal abscesses together with urolithiasis. Urine, blood and abscess cultures yielded C. albicans. The patient was treated with fl uconazole and percutaneous drainage of the perirenal abscess, which was 60 mm in diameter. Her serum creatinine returned to the normal ranges within two weeks of hospitalization. Nearly 18 months following this presentation, she has normal serum creatinine and no abscesses in the kidneys.

  11. Performance of commercial latex agglutination tests for the differentiation of Candida dubliniensis and Candida albicans in routine diagnostics.

    Science.gov (United States)

    Chryssanthou, E; Fernandez, V; Petrini, B

    2007-11-01

    Candida dubliniensis is phenotypically similar to Candida albicans and may therefore be underdiagnosed in the clinical microbiology laboratory. The performance of Bichro-Dubli latex agglutination test for rapid species identification of C. dubliniensis was prospectively evaluated on 111 vaginal and 118 respiratory isolates. These had presumptively been identified as C. albicans/C. dubliniensis by their green colonies on CHROMagar Candida plates. Bichro-Dubli test identifed 2 (1.8%) vaginal and 6 (5.1%) respiratory isolates as C. dubliniensis. The test was also positive for 37 C. dubliniensis control strains characterised by 18S-28S DNA-sequencing. Bichro-Dubli test is thus a sensitive and accurate tool for rapid diagnostics in routine laboratories. PMID:18092961

  12. Genetic relatedness and antifungal susceptibility profile of Candida albicans isolates from fungaemia patients.

    Science.gov (United States)

    Costa-de-Oliveira, Sofia; Sousa, Inês; Correia, Alexandra; Sampaio, Paula; Pais, Célia; Rodrigues, Acácio Gonçalves; Pina-Vaz, Cidália

    2011-04-01

    A prospective study to assess fungaemia was conducted for 12 months at a Portuguese University Hospital. A total of 35 Candida albicans isolates obtained from 12 patients with fungaemia were compared by a multiplex PCR system using four microsatellite loci. Blood isolates were evaluated against concomitant isolates from urine, lower respiratory secretions and central venous catheters, as well as with successive isolates recovered from recurrent episodes of fungaemia. The data analyzed included the department of admission, underlying diseases and antifungal therapy. The susceptibility phenotypes of all isolates to amphotericin B, fluconazole, itraconazole, voriconazole and caspofungin were determined according to the CLSI M27-A3 protocol. We observed a high degree of similarity between successive blood isolates and between blood and concomitant isolates from other sites of the same patient. This is suggestive of the recurrence of fungaemia and was due to the same strain, possibly as a result of the failure of antifungal therapy. The genetic similarity observed between some strains isolated from different patients suggested the likelihood that they were hospital acquired. Distinct patients were infected by the same strain at different time periods, and an increase in antifungal resistance was observed over time for some of these strains. Hospital-acquired exogenous nosocomial infections can be associated with higher risks of antifungal resistance and need to be closely monitored. Particular attention should also be given to endogenous non-blood Candida isolates which can be critical in high risk patients, as they often can become invasive in immunodeficient individuals.

  13. Physical-chemical and microbiological stability of biotherapy Candida albicans RC in different potencies

    Directory of Open Access Journals (Sweden)

    Sheila Garcia

    2011-09-01

    Full Text Available Introduction: Oral Candidiasis is an opportunist fungal infection, with high incidence in HIV and immunosuppressed patients and Candida albicans is the most common causing agent. In some cases, it can evolve to resistant injuries to antifungal conventional therapy. According to Brazilian Homeopathic Pharmacopeia (BHP [1], biotherapic medicines are prepared from chemically undefined biological products. Biotherapics created by Brazilian doctor Roberto Costa (RC have a different homeopathic compounding technique, as its dynamization starts from the ethiologic agent of the illness in its alive form, which present higher capability to stimulate the host immunological system [2,3]. Aim: The goal of this study was evaluate the physical-chemical and microbiological stability of Candida albicans RC potencies under different conditions of storage. Methodology: To prepare the biotherapics, one part of Candida albicans yeast suspension (109 cell/ml was diluted in 9 parts of sterile distillated water. After preparing this 1:10 dilution, the sample was undergone 100 succussions, resulting in the first decimal dilution (1x. Then, one part of this solution was diluted in 9 parts of sterile distillated water and submitted to 100 succussions, generating the 2x. This process was successively repeated following BHP, until 30x. Water 30x was prepared by the same technique, as control. All the solutions were prepared in aseptic and sterile conditions. Biotherapics 6x, 12x, 18x, 24x, 30x and water 30x were storage under refrigeration (2 to 8°C and at room temperate (25°C during 8 weeks. Every 15 days, the following parameters were analyzed: pH, electrical conductivity, UV absorbance (260 and 280 nm. Microbiological analyses were performed after 3 weeks by colony forming unit (CFU method [4]. Results: The preliminary analyses performed at times zero, 15, 30 and 45 days suggest that electrical conductivity of these solutions tend to increase

  14. [25S intron analysis followed by restriction enzyme digestion performed for genotyping Candida albicans isolates].

    Science.gov (United States)

    Karahan, Zeynep Ceren; Saran, Begüm; Yenice, Sevinç; Ağırbaşlı, Handan; Arıkan Akan, Ozay; Tekeli, Alper

    2012-04-01

    Candida albicans is the most frequently encountered fungal pathogen especially in the immunocompromised hosts. Genotyping clinical microbial isolates is important for obtaining epidemiological data and for establishing appropriate infection control strategies in the hospital setting. 25S intron analysis is an easy and reliable method used for genotyping C.albicans strains. As it has a low discriminatory power, its use is limited in epidemiological studies. In this study, our aim was to genotype clinical C.albicans isolates by using 25S intron analysis followed by restriction enzyme digestion in order to develop a more discriminative genotyping system for C.albicans. A total of 260 clinical C.albicans strains isolated from various infection sites (121 blood, 69 sputum, 36 vaginal discharge, 26 wound, 8 urine samples) were genotyped by 25S intron analysis, and all the products obtained by polymerase chain reaction (PCR) were digested with HaeIII restriction enzyme. Discriminatory power of each method was calculated. Among the isolates 184 (70.8%) were classified as genotype A, 42 (16.2%) as genotype B, and 34 (13%) as genotype C by 25S intron analysis. Discriminatory power of the method was calculated as 0.46. HaeIII restriction of genotype A, B and C isolates produced ten, one, and five restriction patterns (genotypes), respectively. By the addition of restriction enzyme analysis, the number of genotypes obtained was increased to 16, and the discriminatory power of the method to 0.79. Combining different genotyping methods increases the discriminatory power by increasing the number of genotypes obtained. However, there is also a risk to split certain strains in different genotypes by the different methods used and this makes the genotypic evaluation more difficult. On the other hand, combining 25S intron analysis with restriction enzyme analysis increases the discriminatory power without introducing a totally different method, and makes the method more suitable for

  15. Shuttle vectors for facile gap repair cloning and integration into a neutral locus in Candida albicans

    OpenAIRE

    Gerami-Nejad, Maryam; Zacchi, Lucia F.; McClellan, Mark; Matter, Kathleen; Berman, Judith

    2013-01-01

    Candida albicans is the most prevalent fungal pathogen of humans. The current techniques used to construct C. albicans strains require integration of exogenous DNA at ectopic locations, which can exert position effects on gene expression that can confound the interpretation of data from critical experiments such as virulence assays. We have identified a large intergenic region, NEUT5L, which facilitates the integration and expression of ectopic genes. To construct and integrate inserts int...

  16. Human submandibular-sublingual saliva promotes adhesion of Candida albicans to polymethylmethacrylate.

    OpenAIRE

    Edgerton, M; Scannapieco, F A; Reddy, M. S.; Levine, M J

    1993-01-01

    The purpose of this study was to identify components of saliva that interact with Candida albicans in solution and that may modulate adhesion to dental acrylic (polymethylmethacrylate [PMMA]) surfaces. Saliva-derived pellicles extracted from C. albicans blastoconidia and hyphal-form cells mixed with fresh human submandibular-sublingual saliva (HSMSL) contained predominantly high- and low-molecular-weight mucins (MG1 and MG2, respectively). In contrast, few components from fresh human parotid ...

  17. Modulation der Candida albicans Biofilmbildung und Expression von Pathogenitätsfaktoren durch Lactobacillus spp.

    OpenAIRE

    Dreßel, Tilmann

    2014-01-01

    Lactobacillus- Spezies, die zur Gattung der Milchsäurebakterien gehören, haben bereits hemmende Eigenschaften gegen Candida albicans gezeigt. Dieser dimorphe Hefepilz ist einer der bedeutendsten Erreger von Pilzinfektionen beim Menschen und einer der häufigsten Verursacher Katheter- assoziierter Infektionen. Eine bedeutende Rolle bei der Pathogenität von C. albicans spielt die Biofilmbildung, die sowohl die körpereigene Abwehr als auch die antimykotische Therapie einer invasiven Infektion erh...

  18. New aniline blue dye medium for rapid identification and isolation of Candida albicans.

    OpenAIRE

    Goldschmidt, M C; Fung, D Y; Grant, R; White, J.; Brown, T

    1991-01-01

    Organic dyes have long been used in diagnostic microbiology to differentiate species by color reactions. We studied the ability of a new noninhibitory medium, YM agar containing 0.01% aniline blue WS dye, Colour Index 42780 (YMAB), to identify Candida albicans among 1,554 yeast specimens obtained from seven clinical laboratories. Appropriate American Type Culture Collection and other characterized strains served as controls. A total of 487 of the clinical strains were identified as C. albican...

  19. Formation of Azole-Resistant Candida albicans by Mutation of Sterol 14-Demethylase P450

    OpenAIRE

    Asai, Kentaro; Tsuchimori, Noboru; Okonogi, Kenji; Perfect, John R.; Gotoh, Osamu; Yoshida, Yuzo

    1999-01-01

    The sterol 14-demethylase P450 (CYP51) of a fluconazole-resistant isolate of Candida albicans, DUMC136, showed reduced susceptibility to this azole but with little change in its catalytic activity. Twelve nucleotide substitutions, resulting in four amino acid changes, were identified in the DUMC136 CYP51 gene in comparison with a reported CYP51 sequence from a wild-type, fluconazole-susceptible C. albicans strain. Seven of these substitutions, including all of those causing amino acid changes...

  20. Prothioconazole and Prothioconazole-Desthio Activities against Candida albicans Sterol 14-α-Demethylase

    OpenAIRE

    Parker, Josie E.; Warrilow, Andrew G. S.; Cools, Hans J; Fraaije, Bart A.; Lucas, John A.; Rigdova, Katarina; Griffiths, William J.; Kelly, Diane E.; Kelly, Steven L.

    2013-01-01

    Prothioconazole is a new triazolinthione fungicide used in agriculture. We have used Candida albicans CYP51 (CaCYP51) to investigate the in vitro activity of prothioconazole and to consider the use of such compounds in the medical arena. Treatment of C. albicans cells with prothioconazole, prothioconazole-desthio, and voriconazole resulted in CYP51 inhibition, as evidenced by the accumulation of 14α-methylated sterol substrates (lanosterol and eburicol) and the depletion of ergosterol. We the...

  1. Modulation of Post-Antibiotic Bacterial Community Reassembly and Host Response by Candida albicans

    OpenAIRE

    Erb Downward, John R.; Falkowski, Nicole R.; Mason, Katie L.; Ryan Muraglia; Huffnagle, Gary B.

    2013-01-01

    The introduction of Candida albicans into cefoperazone-treated mice results in changes in bacterial community reassembly. Our objective was to use high-throughput sequencing to characterize at much greater depth the specific changes in the bacterial microbiome. The colonization of C. albicans significantly altered bacterial community reassembly that was evident at multiple taxonomic levels of resolution. There were marked changes in the levels of Bacteriodetes and Lactobacillaceae. Lachnospir...

  2. An iron homeostasis regulatory circuit with reciprocal roles in Candida albicans commensalism and pathogenesis

    OpenAIRE

    Chen, Changbin; Pande, Kalyan; French, Sarah D.; Tuch, Brian B.; Noble, Suzanne M.

    2011-01-01

    The mammalian gastrointestinal tract and bloodstream are highly disparate biological niches that differ in concentrations of nutrients such as iron. However, some commensal-pathogenic microorganisms, such as the yeast Candida albicans, thrive in both environments. We report the evolution of a transcription circuit in C. albicans that controls iron uptake and determines its fitness in both niches. Our analysis of DNA-binding proteins that regulate iron uptake by this organism suggests the evol...

  3. Factors affecting colonization and dissemination of Candida albicans from the gastrointestinal tract of mice.

    OpenAIRE

    Ekenna, O; Sherertz, R J

    1987-01-01

    Male ICR Swiss mice (2 to 3 months old) were fed Candida albicans in their drinking water for 3 days, followed by no treatment, antibiotics in their drinking water (daily), or immunosuppressants given by intraperitoneal injection (two to three times weekly) over a 3- to 4-week period. The organs of animals were processed to determine the numbers of C. albicans and total aerobic bacteria per g of tissue. Untreated animals had mean Candida counts during the 1-month period of 10(2.3) CFU/g of ce...

  4. The synthesis and synergistic antifungal effects of chalcones against drug resistant Candida albicans.

    Science.gov (United States)

    Wang, Yuan-Hua; Dong, Huai-Huai; Zhao, Fei; Wang, Jie; Yan, Fang; Jiang, Yuan-Ying; Jin, Yong-Sheng

    2016-07-01

    To identify effective and low toxicity synergistic antifungal compounds, 24 derivatives of chalcone were synthesized to restore the effectiveness of fluconazole against fluconazole-resistant Candida albicans. The minimal inhibitory concentration (MIC80) and the fractional inhibitory concentration index (FICI) of the antifungal synergist fluconazole were measured against fluconazole-resistant Candida albicans. This was done via methods established by the clinical and laboratory standards institute (CLSI). Of the synthesized compounds, 2'-hydroxy-4'-methoxychalcone (8) exhibited the most potent in vitro (FICI=0.007) effects. The structure activity relationship of the compounds are then discussed. PMID:27210436

  5. Yeasts isolated from Algerian infants's feces revealed a burden of Candida albicans species, non-albicans Candida species and Saccharomyces cerevisiae.

    Science.gov (United States)

    Seddik, Hamza Ait; Ceugniez, Alexandre; Bendali, Farida; Cudennec, Benoit; Drider, Djamel

    2016-01-01

    This study aimed at showing the yeast diversity in feces of Algerian infants, aged between 1 and 24 months, hospitalized at Bejaia hospital (northeast side of the country). Thus, 20 colonies with yeast characteristics were isolated and identified using biochemical (ID32C Api system) and molecular (sequencing of ITS1-5.8S-ITS2 region) methods. Almost all colonies isolated (19 strains) were identified as Candida spp., with predominance of Candida albicans species, and one strain was identified as Saccharomyces cerevisiae. Screening of strains with inhibitory activities unveiled the potential of Candida parapsilosis P48L1 and Candida albicans P51L1 to inhibit the growth of Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 25923. Further studies performed with these two Candida strains revealed their susceptibility to clinically used antifungal compounds and were then characterized for their cytotoxicity and hemolytic properties. On the other hand, Saccharomyces cerevisiae P9L1 isolated as well in this study was shown to be devoid of antagonism but resulted safe and overall usable as probiotic.

  6. Frequency, pathogenicity and microbiologic outcome of non-Candida albicans candiduria.

    Science.gov (United States)

    Occhipinti, D J; Gubbins, P O; Schreckenberger, P; Danziger, L H

    1994-06-01

    A retrospective review of urine cultures obtained from patients at the University of Illinois Hospital revealed that the frequency of isolation of non-albicans Candida species increased significantly from 1990 to 1991 (p = 0.0003), while the frequency of isolation of Candida albicans species decreased significantly (p = 0.0006). Patients with urine cultures positive for non-albicans Candida species of Torulopsis glabrata during 1991 were identified for review. Sixty-seven patients were eligible for evaluation. Non-albicans candiduria developed in an average of 12 days. Identical fungal species were isolated from the blood following a positive urine culture in only two patients. Twenty patients were treated; candiduria persisted in 9 (45%), while resolution occurred in 11 (55%). The remaining 47 patients were not treated. Non-albicans candiduria persisted in 30 (64%) of these patients and resolved in 15 (32%); in the remaining two patients (4%) the microbiologic outcome was undetermined. The difference in microbiologic outcomes between treated and untreated patients was not significant using the Chi-square test (p = 0.170). Non-albicans candiduria developed rapidly, frequently persisted whether treated or untreated, and rarely progressed to candidemia.

  7. Study on the comparative activity of echinocandins on murine gut colonization by Candida albicans.

    Science.gov (United States)

    Maraki, Sofia; Hamilos, George; Dimopoulou, Dimitra; Andrianaki, Angeliki M; Karageorgiadis, Alexander Steven; Kyvernitakis, Andreas; Lionakis, Stelios; Kofteridis, Diamantis P; Samonis, George

    2015-08-01

    Colonization of the gastrointestinal (GI) tract by Candida species is a principal pathogenetic event for development of invasive candidiasis. Importantly, the effect of echinocandins, the preferred antifungal agents for treatment of invasive candidiasis, on GI tract colonization by Candida spp. is currently unknown. Herein, we used an established model of persistent murine GI tract colonization by Candida albicans to test the ability of different echinocandins to eradicate the yeast from murine gut. Adult male Crl:CD1 (ICR) BR mice were fed with chow containing C. albicans and subsequently treated with different echinocandins or normal saline via daily intraperitoneal injections for 10 days. Quantitative stool cultures were performed immediately before (week one), and weekly for three months after discontinuation of treatment. Notably, treatment with all three echinocandins used (caspofungin, anidulafungin, and micafungin) resulted in eradication of Candida albicans from the stools, as evidenced by the significant reduction of yeast cells from a mean of 4.2 log10 CFU/g of stool before treatment (week one of colonization) to undetectable (Candida yeast cells in the stools of control mice. Collectively, the ability of echinocandins to eradicate C. albicans from the stools could have important implications in prophylaxis of high-risk patients for development of invasive candidiasis originating from the GI tract.

  8. Comparative adherence of Candida albicans and Candida dubliniensis to human buccal epithelial cells and extracellular matrix proteins.

    Science.gov (United States)

    Jordan, Rachael P C; Williams, David W; Moran, Gary P; Coleman, David C; Sullivan, Derek J

    2014-04-01

    Candida albicans and Candida dubliniensis are very closely related pathogenic yeast species. Despite their close relationship, C. albicans is a far more successful colonizer and pathogen of humans. The purpose of this study was to determine if the disparity in the virulence of the two species is attributed to differences in their ability to adhere to human buccal epithelial cells (BECs) and/or extracellular matrix proteins. When grown overnight at 30°C in yeast extract peptone dextrose, genotype 1 C. dubliniensis isolates were found to be significantly more adherent to human BECs than C. albicans or C. dubliniensis genotypes 2-4 (P < 0.001). However, when the yeast cells were grown at 37°C, no significant difference between the adhesion of C. dubliniensis genotype 1 and C. albicans to human BECs was observed, and C. dubliniensis genotype 1 and C. albicans adhered to BECs in significantly greater numbers than the other C. dubliniensis genotypes (P < 0.001). Using surface plasmon resonance analysis, C. dubliniensis isolates were found to adhere in significantly greater numbers than C. albicans to type I and IV collagen, fibronectin, laminin, vitronectin, and proline-rich peptides. These data suggest that C. albicans is not more adherent to epithelial cells or matrix proteins than C. dubliniensis and therefore other factors must contribute to the greater levels of virulence exhibited by C. albicans.

  9. Inhibitory Effect of Alpha-Mangostin on Adhesion of Candida albicans to Denture Acrylic

    Science.gov (United States)

    Kaomongkolgit, Ruchadaporn; Jamdee, Kusuma

    2015-01-01

    Objective: Candida-associated denture stomatitis is a very common disease affecting denture wearers. It is characterized by the presence of yeast biofilm on the denture, primarily associated with C. albicans. The investigation of agents that can reduce C. albicans adhesion may represent a significant advancement in the prevention and treatment of this disease. This study aims to investigate the effect of alpha-mangostin on the in vitro adhesion of C. albicans to denture acrylic and germ tube formation by C. albicans and to compare its activity with clotrimazole which is a topical antifungal agent commonly used for the treatment of Candida-associated denture stomatitis. Materials and Methodology: Alpha-mangostin was extracted by thin layer chromatography. The effect of alpha-mangostin on adhesion of C. albicans to denture acrylic was determined by using a colorimetric tetrazolium assay and germ tube formation by C. albicans was determined by using the counting chamber. Results: A significant reduction of C. albicans adhesion to denture acrylic was evident after exposure to 2,000 µg/ml of alpha-mangostin for only 15 min. In addition, the 2,000 µg/ml of the alpha-mangostin-treated C. albicans had a reduced ability for germ tube formation. These inhibitory effects of alpha-mangostin were as effective as clotrimazole. Conclusion: Alpha-mangostin has antifungal property against C. albicans by inhibiting the adhesion to denture acrylic and germ tube formation in vitro. These results suggest the potential application of alpha-mangostin as a topical medication or a natural oral hygiene product for treatment of Candida-associated denture stomatitis. PMID:26962371

  10. Transcription Factors Efg1 and Bcr1 Regulate Biofilm Formation and Virulence during Candida albicans-Associated Denture Stomatitis.

    Science.gov (United States)

    Yano, Junko; Yu, Alika; Fidel, Paul L; Noverr, Mairi C

    2016-01-01

    Denture stomatitis (DS) is characterized by inflammation of the oral mucosa in direct contact with dentures and affects a significant number of otherwise healthy denture wearers. The disease is caused by Candida albicans, which readily colonizes and form biofilms on denture materials. While evidence for biofilms on abiotic and biotic surfaces initiating Candida infections is accumulating, a role for biofilms in DS remains unclear. Using an established model of DS in immunocompetent animals, the purpose of this study was to determine the role of biofilm formation in mucosal damage during pathogenesis using C. albicans or mutants defective in morphogenesis (efg1-/-) or biofilm formation (bcr1-/-). For in vivo analyses, rats fitted with custom dentures, consisting of fixed and removable parts, were inoculated with wild-type C. albicans, mutants or reconstituted strains and monitored weekly for fungal burden (denture and palate), body weight and tissue damage (LDH) for up to 8 weeks. C. albicans wild-type and reconstituted mutants formed biofilms on dentures and palatal tissues under in vitro, ex vivo and in vivo conditions as indicated by microscopy demonstrating robust biofilm architecture and extracellular matrix (ECM). In contrast, both efg1-/- and bcr1-/- mutants exhibited poor biofilm growth with little to no ECM. In addition, quantification of fungal burden showed reduced colonization throughout the infection period on dentures and palates of rats inoculated with efg1-/-, but not bcr1-/-, compared to controls. Finally, rats inoculated with efg1-/- and bcr1-/- mutants had minimal palatal tissue damage/weight loss while those inoculated with wild-type or reconstituted mutants showed evidence of tissue damage and exhibited stunted weight gain. These data suggest that biofilm formation is associated with tissue damage during DS and that Efg1 and Bcr1, both central regulators of virulence in C. albicans, have pivotal roles in pathogenesis of DS.

  11. Transcription Factors Efg1 and Bcr1 Regulate Biofilm Formation and Virulence during Candida albicans-Associated Denture Stomatitis.

    Directory of Open Access Journals (Sweden)

    Junko Yano

    Full Text Available Denture stomatitis (DS is characterized by inflammation of the oral mucosa in direct contact with dentures and affects a significant number of otherwise healthy denture wearers. The disease is caused by Candida albicans, which readily colonizes and form biofilms on denture materials. While evidence for biofilms on abiotic and biotic surfaces initiating Candida infections is accumulating, a role for biofilms in DS remains unclear. Using an established model of DS in immunocompetent animals, the purpose of this study was to determine the role of biofilm formation in mucosal damage during pathogenesis using C. albicans or mutants defective in morphogenesis (efg1-/- or biofilm formation (bcr1-/-. For in vivo analyses, rats fitted with custom dentures, consisting of fixed and removable parts, were inoculated with wild-type C. albicans, mutants or reconstituted strains and monitored weekly for fungal burden (denture and palate, body weight and tissue damage (LDH for up to 8 weeks. C. albicans wild-type and reconstituted mutants formed biofilms on dentures and palatal tissues under in vitro, ex vivo and in vivo conditions as indicated by microscopy demonstrating robust biofilm architecture and extracellular matrix (ECM. In contrast, both efg1-/- and bcr1-/- mutants exhibited poor biofilm growth with little to no ECM. In addition, quantification of fungal burden showed reduced colonization throughout the infection period on dentures and palates of rats inoculated with efg1-/-, but not bcr1-/-, compared to controls. Finally, rats inoculated with efg1-/- and bcr1-/- mutants had minimal palatal tissue damage/weight loss while those inoculated with wild-type or reconstituted mutants showed evidence of tissue damage and exhibited stunted weight gain. These data suggest that biofilm formation is associated with tissue damage during DS and that Efg1 and Bcr1, both central regulators of virulence in C. albicans, have pivotal roles in pathogenesis of DS.

  12. Adherence of Candida albicans to oral epithelial cells differentiated by Papanicolaou staining.

    OpenAIRE

    Williams, D. W.; Walker, R; Lewis, M.A.; Allison, R T; Potts, A J

    1999-01-01

    OBJECTIVE: To examine the relative adherence of Candida albicans to oral epithelial cells differentiated by Papanicolaou staining. METHODS: Oral epithelial cells were collected from 10 healthy adults (five male, five female) and counted. Equal volumes of oral epithelial cells and candida were mixed and incubated. The epithelial cells from this mix were collected by filtration through 10 microns polycarbonate membrane filters. Cells retained on the membrane filters were stained with crystal vi...

  13. Effect of surface treatments of titanium on amphotericin B-treated Candida albicans persister cells

    OpenAIRE

    Tsang, CSP; Tang, DYK

    2010-01-01

    Although persister cells in Candida albicans biofilm may contribute to its increased resistance to antifungal drugs, little information is available on the formation of Candida persister cells on titanium surfaces. The effect of different surface treatments of Ti on persister cells was determined in the present study. Titanium discs were surface-treated by three different methods (Group A - polishing, Group B - sandblasting followed by acid-etching, and Group C - sandblasting alone). Persiste...

  14. Presumptive identification of Candida species other than C. albicans, C. krusei, and C. tropicalis with the chromogenic medium CHROMagar Candida

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    Horvath Lynn L

    2006-01-01

    Full Text Available Abstract Background CHROMagar Candida (CaC is increasingly being reported as a medium used to differentiate Candida albicans from non-albicans Candida (NAC species. Rapid identification of NAC can assist the clinician in selecting appropriate antifungal therapy. CaC is a differential chromogenic medium designed to identify C. albicans, C. krusei, and C. tropicalis based on colony color and morphology. Some reports have proposed that CaC can also reliably identify C. dubliniensis and C. glabrata. Methods We evaluated the usefulness of CaC in the identification of C. dubliniensis, C. famata, C. firmetaria, C. glabrata, C. guilliermondii, C. inconspicua, C. kefyr, C. lipolytica, C. lusitaniae, C. norvegensis, C. parapsilosis, and C. rugosa. Results Most NAC produced colonies that were shades of pink, lavender, or ivory. Several isolates of C. firmetaria and all C. inconspicua produced colonies difficult to differentiate from C. krusei. Most C. rugosa isolates produced unique colonies with morphology like C. krusei except in a light blue-green color. C. glabrata isolates produced small dark violet colonies that could be differentiated from the pink and lavender colors produced by other species. All seventeen isolates of C. dubliniensis produced green colonies similar to those produced by C. albicans. Conclusion C. glabrata and C. rugosa appear distinguishable from other species using CaC. Some NAC, including C. firmetaria and C. inconspicua, could be confused with C. krusei using this medium.

  15. Efficacy of 1% sodium fluoride as a preservative in urine samples containing glucose and Candida albicans.

    Science.gov (United States)

    Lough, P S; Fehn, R

    1993-03-01

    Whether urine samples used in forensic science DUI testing can be compromised by endogenous ethanol production is a recurrent and yet unresolved issue. This study first assessed unpreserved urine samples that were collected, processed, and analyzed repeatedly over 13 to 41 days using a standard gas chromatographic procedure for ethanol analysis. Despite extensive microbial growth, ethanol was not detected in any test sample. The extent of ethanol production in samples supplemented with glucose, Candida albicans, or both was determined to evaluate the potential for ethanol production in urine samples associated with pathological conditions such as urinary tract yeast infections and diabetes mellitus. Ethanol production under each of the above treatment conditions was assessed in the presence and absence of 1% sodium fluoride as a microbial suppressant. Mean ethanol concentrations were determined for unpreserved samples containing urine only (0.003 +/- 0.005 g%), urine plus yeast (0.006 +/- 0.009 g%) and urine plus glucose (0.067 +/- 0.070 g%). Unpreserved samples supplemented with both yeast and glucose attained mean ethanol concentrations of 0.164 +/- 0.057 g% (P urine samples indicates that false DUI convictions due to endogenous ethanol production are very unlikely. And while endogenous ethanol production is possible in the presence of both glucose and contaminating C. albicans, 1% sodium fluoride completely eliminated microbial fermentation.

  16. 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.

  17. Miltefosine is effective against Candida albicans and Fusarium oxysporum nail biofilms in vitro.

    Science.gov (United States)

    Machado Vila, Taissa Vieira; Sousa Quintanilha, Natália; Rozental, Sonia

    2015-11-01

    Onychomycosis is a fungal nail infection that represents ∼50 % of all nail disease cases worldwide. Clinical treatment with standard antifungals frequently requires long-term systemic therapy to avoid chronic disease. Onychomycosis caused by non-dermatophyte moulds, such as Fusarium spp., and yeasts, such as Candida spp., is particularly difficult to treat, possibly due to the formation of drug-resistant fungal biofilms on affected areas. Here, we show that the alkylphospholipid miltefosine, used clinically against leishmaniasis and cutaneous breast metastases, has potent activity against biofilms of Fusarium oxysporum and Candida albicans formed on human nail fragments in vitro. Miltefosine activity was compared with that of commercially available antifungals in the treatment of biofilms at two distinct developmental phases: formation and maturation (pre-formed biofilms). Drug activity towards biofilms formed on nail fragments and on microplate surfaces (microdilution assays) was evaluated using XTT [2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] assays, and drug effects on fingernail biofilms were analysed by scanning electron microscopy (SEM). For F. oxysporum, miltefosine at 8 μg ml- 1 inhibited biofilm formation by 93%, whilst 256 μg ml- 1 reduced the metabolic activity of pre-formed nail biofilms by 93%. Treatment with miltefosine at 1000 μg ml- 1 inhibited biofilm formation by 89% and reduced the metabolic activity of pre-formed C. albicans biofilms by 99%. SEM analyses of biofilms formed on fingernail fragments showed a clear reduction in biofilm biomass after miltefosine treatment, in agreement with XTT results. Our results show that miltefosine has potential as a therapeutic agent against onychomycosis and should be considered for in vivo efficacy studies, especially in topical formulations for refractory disease treatment.

  18. Melanin Externalization in Candida albicans Depends on Cell Wall Chitin Structures▿

    OpenAIRE

    Walker, Claire A; Gómez, Beatriz L.; Mora-Montes, Héctor M.; Mackenzie, Kevin S; Munro, Carol A.; Brown, Alistair J. P.; Gow, Neil A. R.; Kibbler, Christopher C.; Odds, Frank C.

    2010-01-01

    The fungal pathogen Candida albicans produces dark-pigmented melanin after 3 to 4 days of incubation in medium containing l-3,4-dihydroxyphenylalanine (l-DOPA) as a substrate. Expression profiling of C. albicans revealed very few genes significantly up- or downregulated by growth in l-DOPA. We were unable to determine a possible role for melanin in the virulence of C. albicans. However, we showed that melanin was externalized from the fungal cells in the form of electron-dense melanosomes tha...

  19. Anti-fungal activity of Morinda citrifolia (noni extracts against Candida albicans: An in vitro study

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    K Barani

    2014-01-01

    Full Text Available Aim: The aim of this study was to investigate the anti-fungal activity of Morinda citrifolia fruit extract on Candida albicans. Materials and Methods: Juice extract from M. citrifolia fruit was lyophilized and used in anti-fungal testing. Anti-fungal activity of M. citrifolia fruit extract against C. albicans was tested in vitro at various concentrations. The inhibitory effect of M. citrifolia extract on C. albicans was determined by agar culture and applied broth dilution test. Results: M. citrifolia extract at 1000 μg/ml concentration effectively inhibited the growth of C. albicans (16.6 ± 0.3 compared with the positive control - amphotericin B (20.6 ± 0.6. It was found to be a dose-dependent reaction. Conclusion: M. citrifolia fruit extract had an anti-fungal effect on C. albicans and the inhibitory effect varied with concentration.

  20. Growth of Candida albicans in human saliva is supported by low-molecular-mass compounds.

    Science.gov (United States)

    Valentijn-Benz, Marianne; Nazmi, Kamran; Brand, Henk S; van't Hof, Wim; Veerman, Enno C I

    2015-12-01

    Saliva plays a key role in the maintenance of a stable oral microflora. It contains antimicrobial compounds but also functions as a substrate for growth of bacteria under conditions of low external nutrient supply. Besides bacteria, yeasts, in particular Candida albicans, commonly inhabit the oral cavity. Under immunocompromised conditions, instantaneous outgrowth of this yeast occurs in oral carriers of C. albicans, suggesting that this yeast is able to survive in the oral cavity with saliva as sole source of growth substrate. The aim of the present study was to identify the salivary constituents that are used by C. albicans for growth and survival in saliva. In addition, we have explored the effect of growth in saliva on the susceptibility of C. albicans to histatin 5, a salivary antifungal peptide. It was found that C. albicans was able to grow in human saliva without addition of glucose, and in the stationary phase could survive for more than 400 h. Candida albicans grown in saliva was more than 10 times less susceptible for salivary histatin 5 than C. albicans cultured in Sabouraud medium.

  1. Effect of Nitric Oxide on the Antifungal Activity of Oxidative Stress and Azoles Against Candida albicans.

    Science.gov (United States)

    Li, De-Dong; Yang, Chang-Chun; Liu, Ping; Wang, Yan; Sun, Yan

    2016-06-01

    Nitric oxide (NO) is a small molecule with a wide range of biological activities in mammalian and bacteria. However, the role of NO in fungi, especially Candida albicans, is not clear. In this study, we confirmed the generation of endogenous NO in C. albicans, and found that the production of endogenous NO in C. albicans was associated with nitric oxide synthase pathway. Our results further indicated that the production of endogenous NO in C. albicans was reduced under oxidative stress such as menadione or H2O2 treatment. Meanwhile, exogenous NO donor, sodium nitroprusside (SNP), synergized with H2O2 against C. albicans. Interestingly, SNP could inhibit the antifungal effect of azoles against C. albicans in vitro, suggesting that NO might be involved in the resistance of C. albicans to antifungals. Collectively, this study demonstrated the production of endogenous NO in C. albicans, and indicated that NO may play an important role in the response of C. albicans to oxidative stress and azoles. PMID:27570314

  2. Chronic Candida albicans Meningitis in a 4-Year-Old Girl with a Homozygous Mutation in the CARD9 Gene (Q295X).

    Science.gov (United States)

    Herbst, Martin; Gazendam, Roel; Reimnitz, Denise; Sawalle-Belohradsky, Julie; Groll, Andreas; Schlegel, Paul-Gerhardt; Belohradsky, Bernd; Renner, Ellen; Klepper, Jörg; Grimbacher, Bodo; Kuijpers, Taco; Liese, Johannes

    2015-09-01

    A 4-year-old Turkish girl of consanguineous parents was hospitalized for the evaluation of headaches and recurrent febrile episodes of unknown origin. Her medical history was unremarkable except for a few episodes of uncomplicated oral thrush. Meningitis was diagnosed, and Candida albicans was the only pathogen identified by polymerase chain reaction and culture. Despite systemic antifungal multidrug therapy, a prolonged course of 16 months of therapy was necessary to clear C. albicans from the cerebrospinal fluid. Molecular genetic analysis revealed a homozygous caspase recruitment domain 9 (CARD9) mutation (Q295X), which was reported to predispose to chronic mucocutaneous candidiasis. Immunologic workup excluded predisposing B-cell and T-cell defects. In addition, T cells producing interleukin-17 were repeatedly measured within the normal range. Analyses of neutrophils demonstrated normal nicotinamide adenine dinucleotide phosphate oxidase activity in response to various stimuli including Staphylococcus aureus and C. albicans. Additional neutrophilic functional testing, however, showed a decreased cytotoxicity to nonopsonized C. albicans, indicating an impaired killing mechanism against Candida spp. independent from the production of reactive oxygen species by the nicotinamide adenine dinucleotide phosphate oxidase system. Because this defect was only demonstrated in the absence of opsonins, it might especially predispose to chronic C. albicans infections in the central nervous system where opsonin concentrations are usually low. We, therefore, suggest that due to an additional neutrophil dependent defect CARD9 deficiency predisposes not only to chronic mucocutaneous candidiasis, but also to invasive chronic Candida infections, especially of the central nervous system.

  3. Chronic Candida albicans Meningitis in a 4-Year-Old Girl with a Homozygous Mutation in the CARD9 Gene (Q295X).

    Science.gov (United States)

    Herbst, Martin; Gazendam, Roel; Reimnitz, Denise; Sawalle-Belohradsky, Julie; Groll, Andreas; Schlegel, Paul-Gerhardt; Belohradsky, Bernd; Renner, Ellen; Klepper, Jörg; Grimbacher, Bodo; Kuijpers, Taco; Liese, Johannes

    2015-09-01

    A 4-year-old Turkish girl of consanguineous parents was hospitalized for the evaluation of headaches and recurrent febrile episodes of unknown origin. Her medical history was unremarkable except for a few episodes of uncomplicated oral thrush. Meningitis was diagnosed, and Candida albicans was the only pathogen identified by polymerase chain reaction and culture. Despite systemic antifungal multidrug therapy, a prolonged course of 16 months of therapy was necessary to clear C. albicans from the cerebrospinal fluid. Molecular genetic analysis revealed a homozygous caspase recruitment domain 9 (CARD9) mutation (Q295X), which was reported to predispose to chronic mucocutaneous candidiasis. Immunologic workup excluded predisposing B-cell and T-cell defects. In addition, T cells producing interleukin-17 were repeatedly measured within the normal range. Analyses of neutrophils demonstrated normal nicotinamide adenine dinucleotide phosphate oxidase activity in response to various stimuli including Staphylococcus aureus and C. albicans. Additional neutrophilic functional testing, however, showed a decreased cytotoxicity to nonopsonized C. albicans, indicating an impaired killing mechanism against Candida spp. independent from the production of reactive oxygen species by the nicotinamide adenine dinucleotide phosphate oxidase system. Because this defect was only demonstrated in the absence of opsonins, it might especially predispose to chronic C. albicans infections in the central nervous system where opsonin concentrations are usually low. We, therefore, suggest that due to an additional neutrophil dependent defect CARD9 deficiency predisposes not only to chronic mucocutaneous candidiasis, but also to invasive chronic Candida infections, especially of the central nervous system. PMID:25933095

  4. Genome-wide expression profiling of the response to terbinafine in Candida albicans using a cDNA microarray analysis

    Institute of Scientific and Technical Information of China (English)

    ZENG Yue-bin; QIAN Yuan-shu; MA Lian; GU Hong-ni

    2007-01-01

    Background Candida albicans is the most frequently seen opportunistic human fungal pathogen. Terbinafine is an allylamine antifungal agent that has been proven to have high clinical efficacy in the therapy of fungal infections, the mechanism of action of terbinafine involves the specific inhibition of fungal squalene epoxidase, resulting in ergosterol deficiency and accumulation of intracellular squalene. We used cDNA microarray analysis technology to monitor global expression profile changes of Candida albicans genes in response to terbinafine treatment, and we anticipated a panoramic view of the responses of Candida albicans cells to the representatives of allylamine antifungal agents at the molecular level in an effort to identify drug class-specific and mechanism-independent changes in gene expression.Methods Candida albicans strain ATCC 90028 was exposed to either medium alone or terbinafine at a concentration equivalent to the 1/2 minimal inhibitory concentrations (MICs, 4 mg/L) for 90 minutes. RNA was isolated and gene expression profiles were compared to identify the changes in the gene expression profile using a cDNA microarray analysis. Differential expression of 10 select genes detected by cDNA microarray analysis was confirmed by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR).Results A total of 222 genes were found to be responsive to terbinafine, including 121 up-regulated genes and 101 down-regulated genes. These included genes encoding membrane transport proteins belonging to the members of the ATP-binding cassette (ABC) or major facilitator superfamily (MFS; CDR1, AGP2, GAP6, PHO84, HOL3, FCY23, VCX1),genes involved in stress response and detoxification (CDR1, AGP2, HOL3), and gene involved in the ergosterol biosynthesis pathway (ERG12). The results of semi-quantitative RT-PCR were consistent with that of the cDNA microarray analysis.Conclusions The up-regulation of the gene encoding the multidrug resistance efflux pump

  5. Phenotypic plasticity regulates Candida albicans interactions and virulence in the vertebrate host

    Directory of Open Access Journals (Sweden)

    Emily M Mallick

    2016-05-01

    Full Text Available Phenotypic diversity is critical to the lifestyles of many microbial species, enabling rapid responses to changes in environmental conditions. In the human fungal pathogen Candida albicans, cells exhibit heritable switching between two phenotypic states, white and opaque, which yield differences in mating, filamentous growth, and interactions with immune cells in vitro. Here, we addressed the in vivo properties of the two cell states in a zebrafish model of infection. Multiple attributes were compared including the stability of phenotypic states, filamentation, virulence, dissemination, and phagocytosis by immune cells, and phenotypes equated across three different host temperatures. We show that both white and opaque cells can establish a lethal systemic infection. The relative virulence of the two cell types is temperature dependent; virulence is similar at 25°C, but at higher temperatures (30 and 33°C white cells are significantly more virulent than opaque cells. Despite the difference in virulence, fungal burdens and dissemination are similar between cells in the two states. Additionally, both white and opaque cells exhibit robust filamentation during infection, and mutants unable to filament show decreased virulence, establishing that this program is critical for pathogenesis in both cell states. Interactions between C. albicans cells and immune cells were compared both in vitro and in vivo. Macrophages and neutrophils preferentially phagocytosed white cells over opaque cells in vitro, and neutrophils also showed preferential phagocytosis of white cells in vivo. Together, these studies distinguish the properties of white and opaque cells in a vertebrate host, and establish that the two cell types demonstrate both important similarities and key differences during infection.

  6. Invasive infection in an acute myeloblastic leukemia patient due to triazole-resistant Candida tropicalis.

    Science.gov (United States)

    de Carvalho Parahym, Ana Maria Rabelo; da Silva, Carolina Maria; Leão, Mariele Porto Carneiro; Macario, Michele Chianca; Filho, Gustavo Antônio da Trindade Meira Henriques; de Oliveira, Neiva Tinti; Neves, Rejane Pereira

    2011-11-01

    Non-albicans Candida species are being increasingly reported as causes of nosocomial fungal infections. For example, invasive candidiasis caused by C. tropicalis has been associated with hematologic malignancies. In this study, we report a fatal case of fungemia and a possible urinary and pulmonary infection in a leukemia patient that was due to a strain of C. tropicalis resistant to 2 triazole antifungals.

  7. 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.

  8. Prospective evaluation of the chromogenic medium CandiSelect 4 for differentiation and presumptive identification of non-Candida albicans Candida species.

    Science.gov (United States)

    Zhao, Liang; de Hoog, G Sybren; Cornelissen, Akke; Lyu, Qian; Mou, Lili; Liu, Taohua; Cao, Yu; Vatanshenassan, Mansoureh; Kang, Yingqian

    2016-02-01

    Rapid identification of pathogenic yeasts is a crucial step in timely and appropriate antifungal therapy. For diagnostics in the clinical laboratory, simplified alternatives to barcoding are needed. CandiSelect 4 (CS4) medium, a chromogenic medium for isolation of clinical yeasts, allows routine recognition of Candida albicans and presumptive identification of Candida tropicalis, Candida glabrata, and Candida krusei. We evaluated an extension of this method with 46 non-Candida albicans Candida (NCAC) and 7 Malassezia species. The medium supported growth of all species tested and a wide diversity of cultural types were observed. Colony colours were in violet, turquoise (including green and blue), or white tinges. Eight NCAC species produced violet pigmentation similar to that of C. albicans. Most NCAC species, including C. glabrata and C. tropicalis were distributed in the turquoise group. Malassezia species were invariably blue.

  9. 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.

  10. Anti-Candida activity of Quercus infectoria gall extracts against Candida species

    OpenAIRE

    Nur Saeida Baharuddin; Hasmah Abdullah; Wan Nor Amilah Wan Abdul Wahab

    2015-01-01

    Background: Galls of Quercus infectoria have been traditionally used to treat common ailments, including yeast infections caused by Candida species. Objective: This study aimed to evaluate the in vitro anti-Candida activity of Q. infectoria gall extracts against selected Candida species. Materials and Methods: Methanol and aqueous extracts of Q. infectoria galls were tested for anti-Candida activity against Candida albicans, Candida krusei, Candida glabrata, Candida parapsilosis and Candida t...

  11. 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.

  12. Antifungal susceptibility analysis of berberine, baicalin, eugenol and curcumin on Candida albicans

    Institute of Scientific and Technical Information of China (English)

    Wu Jianhua; Wen Hai

    2009-01-01

    Objective: To analyze the antifungal effects of Chinese herb monomers, i.e. berberine, baicalin, eugenol and curcumin, on Candida albicans. Methods: After Candida albicans strain Y01-09 was incubated for 48 h in YEPD broth which contained different concentrations of Chinese herb components, the cell cycle, fluorescent intensity and the size of cell volume were detected by flow cytometry. Results: The 4 Chinese herb monomers could affect the cell cycle of Candida albicans in different ranges. The ratio of cells in S-G2-M period decreased as the agents concentration increased, indicating that the cell division was inhibited. The fluorescent intensity of Candida albicans cells became weaker after being incubated, which reflected the loss of DNA fragments. The higher the concentration was, the weaker the fluorescent intensity became. The cell size, cell diopter and particle size changed much as the agents concentration increased. Conclusion: Chinese herb monomers play the antifungal role in inhibiting cell division. FCM could be used to determine the susceptibility of antifungal agents.

  13. In vitro effects of Salvia officinalis L. essential oil on Candida albicans

    Directory of Open Access Journals (Sweden)

    Tularat Sookto

    2013-05-01

    Conclusions: S. officinalis L. essential oil exhibited anticandidal activities against C. albicans and had inhibitory effects on the adhesion of the cells to PMMA resin surface. With further testing and development, S. officinalis essential oil may be used as an antifungal denture cleanser to prevent candidal adhesion and thus reduce the risk of candida-associated denture stomatitis.

  14. Streptococcus mutans Competence-Stimulating Peptide Inhibits Candida albicans Hypha Formation

    NARCIS (Netherlands)

    Jarosz, Lucja M.; Deng, Dong Mei; van der Mei, Henny C.; Crielaard, Wim; Krom, Bastiaan P.

    2009-01-01

    The oral cavity is colonized by microorganisms growing in biofilms in which interspecies interactions take place. Streptococcus mutans grows in biofilms on enamel surfaces and is considered one of the main etiological agents of human dental caries. Candida albicans is also commonly found in the huma

  15. Trapping and Killing of Candida albicans by Corynebacterium parvum-Activated Livers †

    OpenAIRE

    Sawyer, R T; Moon, R J; Beneke, E S

    1981-01-01

    Corynebacterium parvum vaccination significantly increased the number of leukocytes adherent to hepatic vessels. Perfused C. parvum-treated livers killed significantly more Candida albicans than did livers not treated with C. parvum, an effect reversed by the macrophage inhibitors silica, phenylbutazone, and iodoacetate.

  16. Complement plays a central role in Candida albicans-induced cytokine production by human PBMCs

    DEFF Research Database (Denmark)

    Cheng, Shih-Chin; Sprong, Tom; Joosten, Leo A B;

    2012-01-01

    In experimental studies, the role of complement in antifungal host defense has been attributed to its opsonizing capability. In this study, we report that in humans an activated complement system mainly augments Candida albicans-induced host proinflammatory cytokine production via C5a-C5aR signal...

  17. Iron restriction-induced adaptations in the wall proteome of Candida albicans

    NARCIS (Netherlands)

    A.G. Sorgo; S. Brul; C.G. de Koster; L.J. de Koning; F.M. Klis

    2013-01-01

    The opportunistic fungal pathogen Candida albicans has developed various ways to overcome iron restriction in a mammalian host. Using different surface proteins, among them membrane- and wall-localized GPI-proteins, it can exploit iron from host hemoglobin, ferritin, and transferrin. Culturing C. al

  18. Phagocytosis and killing of Candida albicans by human neutrophils after exposure to structurally different lipid emulsions.

    NARCIS (Netherlands)

    Wanten, G.J.A.; Curfs, J.H.A.J.; Meis, J.F.G.M.; Naber, A.H.J.

    2001-01-01

    BACKGROUND: To test the hypothesis that structurally different lipid emulsions have distinct immune-modulating properties, we analyzed the elimination of Candida albicans by neutrophils after exposure to various emulsions. METHODS: Neutrophils from 8 volunteers were incubated in physiologic 5 mmol/L

  19. A Concise Synthesis of Antigenic Factor 4 Existing in Candida albicans

    Institute of Scientific and Technical Information of China (English)

    ZHU,Yu-Liang(朱玉亮); CHEN,Lang-Qiu(陈朗秋); KONG,Fan-Zuo(孔繁祚)

    2001-01-01

    A concise synthesis of α-Man12-α-Man1→3-(α-Man1→6)-α-Man12-α-Man12-a-Man12-Man,the antigenic factot 4 existing in Candida albicans,was achieved via TMSOTf promoted condensation of the corresponding acylated tetrasac charide donor with the trisaccharide acceptor.``

  20. Streptococcus mutans competence-stimulating peptide inhibits Candida albicans hypha formation

    NARCIS (Netherlands)

    L.M. Jarosz; D.M. Deng; H.C. van der Mei; W. Crielaard; B.P. Krom

    2009-01-01

    The oral cavity is colonized by microorganisms growing in biofilms in which interspecies interactions take place. Streptococcus mutans grows in biofilms on enamel surfaces and is considered one of the main etiological agents of human dental caries. Candida albicans is also commonly found in the huma

  1. Host responses to Candida albicans: Th17 cells and mucosal candidiasis

    OpenAIRE

    Conti, Heather R.; Gaffen, Sarah L

    2010-01-01

    Candida albicans causes mucosal and disseminated candidiasis, which represent serious problems for the rapidly expanding immunocompromised population. Until recently, Th1-mediated immunity was thought to confer the primary protection, particularly for oral candidiasis. However, emerging data indicate that the newly-defined Th17 compartment appears to play the predominant role in mucosal candidiasis.

  2. Malassezia and Candida infections in bull terriers with lethal acrodermatitis.

    Science.gov (United States)

    McEwan, N A

    2001-06-01

    In 12 cases of lethal acrodermatitis (LAD), four sampling techniques (brush, swab, scrape and adhesive tape strip) were used to study the distribution of yeasts in various body sites and these results were compared with those from five cases of atopic dermatitis and those of 10 normal dogs. Malassezia was frequently isolated from lesional and non-lesional skin and haircoat, footpads, nails and mucous membranes from dogs with either LAD or atopic dermatitis, although, generally, more Malassezia organisms were isolated from LAD cases. In normal dogs, Malassezia was most frequently recovered from the ear canal and the perianal skin. Candida was isolated frequently from dogs with LAD, but only a single isolate of this yeast was found in the other two groups. Fungal hyphae and pseudohyphae, probably Candida albicans, could be detected in samples collected from the nails and footpads of dogs with LAD. Both Malassezia and Candida could be isolated using all four sampling techniques. The MacKenzie (toothbrush) technique and adhesive tape strip cultures proved simple methods for the semiquantitative evaluation of yeasts. The high recovery rate of Malassezia and Candida from dogs with LAD is probably related to immune dysfunction, particularly T-cell dysfunction, known to be present in these dogs. C albicans infection may in part be responsible for the pathogenic changes of the nails and footpads commonly seen in cases of LAD. PMID:11440398

  3. Nanoparticles and Ethylene Diamine Tetra Acetic Acid on Growth Inhibition of Standard Strain of Candida albicans

    Directory of Open Access Journals (Sweden)

    F Haghighi

    2010-07-01

    Full Text Available Introduction & Objective: In recent years, the incidence of opportunistic fungi has shown a marked increase. Infection caused by common pathogenic fungi is a significant health problem in immune compromised hosts. The present study evaluated antifungal activity of Titanum dioxide nanoparticles and Ethylene Diamine Tetra-acetic Acid against Candida albicans as self-cleaning agent by standard micro dilution test. Materials & Methods: The present study was conducted at the Medical University of Tarbiyat Modares in 2009. TiO2 nanoparticles were obtained through the hydrolysis of TiCl4 (Titanium tetrachloride. Size and type of these nanoparticles were characterized by scanning electron microscopy (SEM and X-Ray-Diffraction (XRD. Afterwards, the Minimum Inhibitory Concentration (MIC and Minimal Fungicide Concentration (MFC test for TiO2 and EDTA were performed. Results: Concentration of synthesised TiO2 was 7.03 mg/ml and 5.63 5.63 ×1020 particles/ml. Evaluation of morphology and diameter of the TiO2 nanoparticles with SEM showed that nanoparticles were spherical with diameter between 40-65 nm. MIC50 of 2.2, 1.24 and 0.125 µg/ml respectively. MIC90 and MFC of TiO2, EDTA and fluconazole were 3.51, 2.48 , 0.5 µg/ml and 4.06, 3.1 ,1 µg/ml respectively. Conclusion: In the present study, using of synthesized TiO2 nanoparticles with chemical method showed