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Sample records for candida albicans hyphae

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

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    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.

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

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    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.

  3. Pseudomonas aeruginosa lipopolysaccharide inhibits Candida albicans hyphae formation and alters gene expression during biofilm development.

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    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

  4. 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

  5. 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

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

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

    1998-01-01

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

  7. 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.

  8. Candida/Candida biofilms. First description of dual-species Candida albicans/C. rugosa biofilm.

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    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.

  9. 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.

  10. 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.

  11. 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.

  12. Skin Immunity to Candida albicans.

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    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

  13. 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.

  14. 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).

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

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    Endang W. Bachtiar

    2014-07-01

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

  16. Candida albicans commensalism in the gastrointestinal tract.

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    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.

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

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    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.

  18. 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.

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

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    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.

  20. In vitro modification of Candida albicans invasiveness.

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    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.

  1. 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.

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

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    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.

  3. 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.

  4. Adaptive immune responses to Candida albicans infection.

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    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.

  5. Development of DNA probes for Candida albicans

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    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.

  6. 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

  7. 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.

  8. 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.)

  9. 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.)

  10. 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

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

    LENUS (Irish Health Repository)

    O'Connor, Leanne

    2010-09-01

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

  12. 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...

  13. 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...

  14. 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.

  15. 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.

  16. 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.

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

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    Apurva K Pathak

    2012-02-01

    Full Text Available OBJECTIVE: In polymicrobial biofilms bacteria extensively interact with Candida species, but the interaction among the different species of the Candida is yet to be completely evaluated. In the present study, the difference in biofilm formation ability of clinical isolates of four species of Candida in both single-species and multi-species combinations on the surface of dental acrylic resin strips was evaluated. MATERIAL AND METHODS: The species of Candida, isolated from multiple species oral candidiasis of the neutropenic patients, were used for the experiment. Organisms were cultured on Sabouraud dextrose broth with 8% glucose (SDB. Biofilm production on the acrylic resins strips was determined by crystal violet assay. Student's t-test and ANOVA were used to compare in vitro biofilm formation for the individual species of Candida and its different multi-species combinations. RESULTS: In the present study, differences between the mean values of the biofilm-forming ability of individual species (C. glabrata>C. krusei>C. tropicalis>C. albicans and in its multi-species' combinations (the highest for C. albicans with C. glabrata and the lowest for all the four species combination were reported. CONCLUSIONS: The findings of this study showed that biofilm-forming ability was found greater for non-Candida albicans Candida species (NCAC than for C. albicans species with intra-species variation. Presence of C. albicans in multi-species biofilms increased, whereas; C. tropicalis decreased the biofilm production with all other NCAC species.

  18. Biofilm formation and Candida albicans morphology on the surface of denture base materials.

    Science.gov (United States)

    Susewind, Sabine; Lang, Reinhold; Hahnel, Sebastian

    2015-12-01

    Fungal biofilms may contribute to the occurrence of denture stomatitis. The objective of the study was to investigate the biofilm formation and morphology of Candida albicans in biofilms on the surface of denture base materials. Specimens were prepared from different denture base materials. After determination of surface properties and salivary pellicle formation, mono- and multispecies biofilm formation including Candida albicans ATCC 10231 was initiated. Relative amounts of adherent cells were determined after 20, 44, 68 and 188 h; C. albicans morphology was analysed employing selective fluorescence microscopic analysis. Significant differences were identified in the relative amount of cells adherent to the denture base materials. Highest blastospore/hyphae index suggesting an increased percentage of hyphae was observed in mono- and multispecies biofilms on the soft denture liner, which did not necessarily respond to the highest relative amount of adherent cells. For both biofilm models, lowest relative amount of adherent cells was identified on the methacrylate-based denture base material, which did not necessarily relate to a significantly lower blastospore/hyphae index. The results indicate that there are significant differences in both biofilm formation as well as the morphology of C. albicans cells in biofilms on the surface of different denture base materials.

  19. 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.

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

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    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.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. Comparison of Switching and Biofilm Formation between MTL-Homozygous Strains of Candida albicans and Candida dubliniensis.

    Science.gov (United States)

    Pujol, Claude; Daniels, Karla J; Soll, David R

    2015-12-01

    Candida albicans and Candida dubliniensis are highly related species that share the same main developmental programs. In C. albicans, it has been demonstrated that the biofilms formed by strains heterozygous and homozygous at the mating type locus (MTL) differ functionally, but studies rarely identify the MTL configuration. This becomes a particular problem in studies of C. dubliniensis, given that one-third of natural strains are MTL homozygous. For that reason, we have analyzed MTL-homozygous strains of C. dubliniensis for their capacity to switch from white to opaque, the stability of the opaque phenotype, CO2 induction of switching, pheromone induction of adhesion, the effects of minority opaque cells on biofilm thickness and dry weight, and biofilm architecture in comparison with C. albicans. Our results reveal that C. dubliniensis strains switch to opaque at lower average frequencies, exhibit a far lower level of opaque phase stability, are not stimulated to switch by high CO2, exhibit more variability in biofilm architecture, and most notably, form mature biofilms composed predominately of pseudohyphae rather than true hyphae. Therefore, while several traits of MTL-homozygous strains of C. dubliniensis appear to be degenerating or have been lost, others, most notably several related to biofilm formation, have been conserved. Within this context, the possibility is considered that C. dubliniensis is transitioning from a hypha-dominated to a pseudohypha-dominated biofilm and that aspects of C. dubliniensis colonization may provide insights into the selective pressures that are involved.

  6. 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.

  7. 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.

  8. 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.

  9. Potent Activities of Roemerine against Candida albicans and the Underlying Mechanisms

    Directory of Open Access Journals (Sweden)

    Chaoyu Ma

    2015-09-01

    Full Text Available Roemerine (RM is an aporphine alkaloid isolated from the fresh rattan stem of Fibraurea recisa, and it has been demonstrated to have certain antifungal activity. This study aimed to investigate the antifungal activity of RM and the underlying mechanisms in Candida albicans (C. albicans. The in vitro antifungal activity of RM was evaluated by a series of experiments, including the XTT reduction assay, confocal laser scanning microscopy assay, scanning electron microscope assay. Results showed that 1 μg/mL RM inhibited biofilm formation significantly (p < 0.01 both in Spider medium and Lee’s medium. In addition, RM could inhibit yeast-to-hyphae transition of C. albicans in a dose-dependent manner. The biofilm-specific and hypha-specific genes such as YWP1, SAP5, SAP6, HWP1, ECE1 were up-regulated and EFG1 was down-regulated after 8 μg/mL RM treatment. Furthermore, the toxicity of RM was investigated using C. elegans worms, three cancer cells and one normal cell. The date showed that RM had no significant toxicity. In conclusion, RM could inhibited the formation of C. albicans biofilm in vitro, but it had no fungicidal effect on planktonic C. albicans cells, and the anti-biofilm mechanism may be related to the cAMP pathway.

  10. 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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

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

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    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.

  14. 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...

  15. Morphogenesis of Candida albicans and Cytoplasmic Proteins Associated with Differences in Morphology, Strain, or Temperature

    OpenAIRE

    1981-01-01

    The extent of change in cytoplasmic proteins which accompanies yeast-to-mycelium morphogenesis of Candida albicans was analyzed by two-dimensional gel electrophoresis. Pure cultures of yeasts and true hyphae (i.e., without concomitant production of pseudohyphae) were grown in a synthetic low-sulfate medium. The two strains selected for this study were strain 4918, which produces pure mycelial cultures in low-sulfate medium at 37 degrees C and yeast cells at 24 degrees C, and strain 2252, whic...

  16. 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.

  17. Immunoproteomic Analysis of Antibody Responses to Extracellular Proteins of Candida albicans Revealing the Importance of Glycosylation for Antigen Recognition.

    Science.gov (United States)

    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

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. 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

  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. Candida albicans keratitis in an immunocompromised patient

    Directory of Open Access Journals (Sweden)

    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

  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. Synthetic arylquinuclidine derivatives exhibit antifungal activity against Candida albicans, Candida tropicalis and Candida parapsilopsis

    Directory of Open Access Journals (Sweden)

    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

  8. 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

  9. 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

  10. CaSfl1 plays a dual role in transcriptional regulation in Candida albicans

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

    As a newly identified transcription factor in Candida albcians, CaSfl1 has been shown to be involved in cell flocculation and filamentation and in the negative regulation of several genes involved in hyphal growth. In this study, we constructed Casfl1△/△ mutants and confirmed that deletion of this gene in-deed affected cell flocculation and filamentation. In addition, by RT-PCR we found that while Casfl1 repressed the expression of several hypha-specific genes including HWP1, ECE1, ALS1, ALS3, and FL08, it strongly activated the expression of the heat-shock protein genes HSP30 and HSP90 under certain stress conditions. Therefore, we propose that CaSfl1 can act as both positive and negative regulators, thereby playing a dual role in transcriptional controls in Candida albicans.

  11. Potent Activities of Roemerine against Candida albicans and the Underlying Mechanisms.

    Science.gov (United States)

    Ma, Chaoyu; Du, Faya; Yan, Lan; He, Gonghao; He, Jianchang; Wang, Chengying; Rao, Gaoxiong; Jiang, Yuanying; Xu, Guili

    2015-01-01

    Roemerine (RM) is an aporphine alkaloid isolated from the fresh rattan stem of Fibraurea recisa, and it has been demonstrated to have certain antifungal activity. This study aimed to investigate the antifungal activity of RM and the underlying mechanisms in Candida albicans (C. albicans). The in vitro antifungal activity of RM was evaluated by a series of experiments, including the XTT reduction assay, confocal laser scanning microscopy assay, scanning electron microscope assay. Results showed that 1 μg/mL RM inhibited biofilm formation significantly (p albicans in a dose-dependent manner. The biofilm-specific and hypha-specific genes such as YWP1, SAP5, SAP6, HWP1, ECE1 were up-regulated and EFG1 was down-regulated after 8 μg/mL RM treatment. Furthermore, the toxicity of RM was investigated using C. elegans worms, three cancer cells and one normal cell. The date showed that RM had no significant toxicity. In conclusion, RM could inhibited the formation of C. albicans biofilm in vitro, but it had no fungicidal effect on planktonic C. albicans cells, and the anti-biofilm mechanism may be related to the cAMP pathway.

  12. 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.

  13. 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.

  14. 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

  15. 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...

  16. 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...

  17. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

  1. 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.

  2. 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.

  3. 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

  4. Co-occurence of filamentation defects and impaired biofilms in Candida albicans protein kinase mutants.

    Science.gov (United States)

    Konstantinidou, Nina; Morrissey, John Patrick

    2015-12-01

    Pathogenicity of Candida albicans is linked with its developmental stages, notably the capacity switch from yeast-like to hyphal growth, and to form biofilms on surfaces. To better understand the cellular processes involved in C. albicans development, a collection of 63 C. albicans protein kinase mutants was screened for biofilm formation in a microtitre plate assay. Thirty-eight mutants displayed some degree of biofilm impairment, with 20 categorised as poor biofilm formers. All the poor biofilm formers were also defective in the switch from yeast to hyphae, establishing it as a primary defect. Five genes, VPS15, IME2, PKH3, PGA43 and CEX1, encode proteins not previously reported to influence hyphal development or biofilm formation. Network analysis established that individual components of some processes, most interestingly MAP kinase pathways, are not required for biofilm formation, most likely indicating functional redundancy. Mutants were also screened for their response to bacterial supernatants and it was found that Pseudomonas aeruginosa supernatants inhibited biofilm formation in all mutants, regardless of the presence of homoserine lactones (HSLs). In contrast, Candida morphology was only affected by supernatant containing HSLs. This confirms the distinct HSL-dependent inhibition of filamentation and the HSL-independent impairment of biofilm development by P. aeruginosa.

  5. 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

  6. 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

  7. 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.

  8. 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...

  9. 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...

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. Inhibition of germ tube's formation of Candida albicans by lactobacillus spp.

    Institute of Scientific and Technical Information of China (English)

    TANG Huan; WEI Hong

    2006-01-01

    Objective:To investigate the effects of 6 strains of lactobacilli and their main culture metabolites on the morphogenesis of Candida albicans (C. albicans) so as to screen medicinal strains as antifungal agents. Methods: Spent culture supernatant (SCS) at different culture time points, live lactobacilli, heatkilled bacteria and bacterial short-chain fatty acids (SCFA) with different molarities were incubated with C. albicans respectively. Crystal violet-based germ tube assay was used to detect the germination of C. albicans and the inhibitory efficiency of each addition was tested by germination rate. Results: SCS of lactobacillus spp. decreased the germination significantly and live bacteria of L. rhamnosus. GG, L. acidophilus L050103-12 as well as L. johnsonii JCM1022 could partially inhibit the conversion, however, all the heatkilled bacteria failed to control the germ tube formation. In addition, only butyric acid blocked the conversion of yeast to hypha among all the SCFA. Conclusion: The excellent fungistasis activities make L.rhamnosus. GG, L. acidophilus L050103-12 and L. johnsonii JCM1022 potential strains as antifungal drugs and the inhibition seems to have direct correlation to the metabolites.

  20. CARD9 Mediates Dectin-2-induced IκBα Kinase Ubiquitination Leading to Activation of NF-κB in Response to Stimulation by the Hyphal Form of Candida albicans*

    OpenAIRE

    Bi, Liangkuan; Gojestani, Sara; Wu, Weihui; Hsu, Yen-Michael S.; Zhu, Jiayuan; Ariizumi, Kiyoshi; Lin, Xin

    2010-01-01

    The scaffold protein CARD9 plays an essential role in anti-fungus immunity and is implicated in mediating Dectin-1/Syk-induced NF-κB activation in response to Candida albicans infection. However, the molecular mechanism by which CARD9 mediates C. albicans-induced NF-κB activation is not fully characterized. Here we demonstrate that CARD9 is involved in mediating NF-κB activation induced by the hyphal form of C. albicans hyphae (Hyphae) but not by its heat-inactivated unicellular form. Our dat...

  1. 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.

  2. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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...

  10. 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.

  11. 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.

  12. Transcript profiling reveals rewiring of iron assimilation gene expression in Candida albicans and C. dubliniensis.

    LENUS (Irish Health Repository)

    Moran, Gary P

    2012-12-01

    Hyphal growth is repressed in Candida albicans and Candida dubliniensis by the transcription factor Nrg1. Transcript profiling of a C. dubliniensis NRG1 mutant identified a common group of 28 NRG1-repressed genes in both species, including the hypha-specific genes HWP1, ECE1 and the regulator of cell elongation UME6. Unexpectedly, C. dubliniensis NRG1 was required for wild-type levels of expression of 10 genes required for iron uptake including seven ferric reductases, SIT1, FTR1 and RBT5. However, at alkaline pH and during filamentous growth in 10% serum, most of these genes were highly induced in C. dubliniensis. Conversely, RBT5, PGA10, FRE10 and FRP1 did not exhibit induction during hyphal growth when NRG1 is downregulated, indicating that in C. dubliniensis NRG1 is also required for optimal expression of these genes in alkaline environments. In iron-depleted medium at pH 4.5, reduced growth of the NRG1 mutant relative to wild type was observed; however, growth was restored to wild-type levels or greater at pH 6.5, indicating that alkaline induction of iron assimilation gene expression could rescue this phenotype. These data indicate that transcriptional control of iron assimilation and pseudohypha formation has been separated in C. albicans, perhaps promoting growth in a wider range of niches.

  13. 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.

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

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    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.

  15. 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.

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

    LENUS (Irish Health Repository)

    Martin, Ronny

    2011-04-01

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

  17. 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.

  18. 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.

  19. 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.

  20. ANTAGONISTIC EFFECT OF EDIBLE MUSHROOM EXTRACT ON CANDIDA ALBICANS GROWTH

    Directory of Open Access Journals (Sweden)

    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.

  1. 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.

  2. Interleukin 17-Mediated Host Defense against Candida albicans

    Directory of Open Access Journals (Sweden)

    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.

  3. 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.

  4. 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

  5. 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

  6. 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

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

    Directory of Open Access Journals (Sweden)

    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.

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

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    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. 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...

  10. 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

  11. Garcinia xanthochymus Benzophenones Promote Hyphal Apoptosis and Potentiate Activity of Fluconazole against Candida albicans Biofilms.

    Science.gov (United States)

    Jackson, Desmond N; Yang, Lin; Wu, ShiBiao; Kennelly, Edward J; Lipke, Peter N

    2015-10-01

    Xanthochymol and garcinol, isoprenylated benzophenones purified from Garcinia xanthochymus fruits, showed multiple activities against Candida albicans biofilms. Both compounds effectively prevented emergence of fungal germ tubes and were also cytostatic, with MICs of 1 to 3 μM. The compounds therefore inhibited development of hyphae and subsequent biofilm maturation. Xanthochymol treatment of developing and mature biofilms induced cell death. In early biofilm development, killing had the characteristics of apoptosis, including externalization of phosphatidyl serine and DNA fragmentation, as evidenced by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) fluorescence. These activities resulted in failure of biofilm maturation and hyphal death in mature biofilms. In mature biofilms, xanthochymol and garcinol caused the death of biofilm hyphae, with 50% effective concentrations (EC50s) of 30 to 50 μM. Additionally, xanthochymol-mediated killing was complementary with fluconazole against mature biofilms, reducing the fluconazole EC50 from >1,024 μg/ml to 13 μg/ml. Therefore, xanthochymol has potential as an adjuvant for antifungal treatments as well as in studies of fungal apoptosis.

  12. Garcinia xanthochymus Benzophenones Promote Hyphal Apoptosis and Potentiate Activity of Fluconazole against Candida albicans Biofilms.

    Science.gov (United States)

    Jackson, Desmond N; Yang, Lin; Wu, ShiBiao; Kennelly, Edward J; Lipke, Peter N

    2015-10-01

    Xanthochymol and garcinol, isoprenylated benzophenones purified from Garcinia xanthochymus fruits, showed multiple activities against Candida albicans biofilms. Both compounds effectively prevented emergence of fungal germ tubes and were also cytostatic, with MICs of 1 to 3 μM. The compounds therefore inhibited development of hyphae and subsequent biofilm maturation. Xanthochymol treatment of developing and mature biofilms induced cell death. In early biofilm development, killing had the characteristics of apoptosis, including externalization of phosphatidyl serine and DNA fragmentation, as evidenced by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) fluorescence. These activities resulted in failure of biofilm maturation and hyphal death in mature biofilms. In mature biofilms, xanthochymol and garcinol caused the death of biofilm hyphae, with 50% effective concentrations (EC50s) of 30 to 50 μM. Additionally, xanthochymol-mediated killing was complementary with fluconazole against mature biofilms, reducing the fluconazole EC50 from >1,024 μg/ml to 13 μg/ml. Therefore, xanthochymol has potential as an adjuvant for antifungal treatments as well as in studies of fungal apoptosis. PMID:26195512

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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.

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

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    Fikadu G Tafesse

    2015-10-01

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

  20. 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.

  1. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Click beetle luciferases as dual reporters of gene expression in Candida albicans.

    Science.gov (United States)

    Kapitan, Mario; Eichhof, Isabel; Lagadec, Quentin; Ernst, Joachim F

    2016-08-01

    Synthetic genes encoding functional luciferases of the click beetle (CB) Pyrophorus plagiophthalamus have been expressed in the human fungal pathogen Candida albicans. Both green- and red-emitting CB luciferases (CaCBGluc and CaCBRluc) were produced with high efficiency in transformants under transcriptional control of the growth-dependent ACT1 promoter, as well as by the HWP1 and UME6 promoters, which are upregulated during hyphal morphogenesis, as well as by the YWP1 and EFG1 promoters, which are downregulated. For all hyphally regulated genes, relative bioluminescence values derived from promoter fusions approximated relative transcript levels of native genes, although downregulation of YWP1 promoter activity required correction for the stability of CB luciferases (approximate half-lives 30 min for CaCBRluc and 80 min for CaCBGluc, as determined by immunoblotting). Importantly, the activity of both luciferases could be separately monitored in a single strain, in intact cells, in lysed cells or in cell extracts using luciferin as single substrate and inhibition of hypha formation by farnesol could be easily detected by the HWP1p-CaCBRluc fusion. The results suggest that CB luciferases are convenient tools to measure gene expression in C. albicans and may facilitate screenings for antifungal compounds. PMID:27339610

  4. 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.

  5. Blocking of Candida albicans biofilm formation by cis-2-dodecenoic acid and trans-2-dodecenoic acid.

    Science.gov (United States)

    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

  6. Roles of Zinc-responsive transcription factor Csr1 in filamentous growth of the pathogenic Yeast Candida albicans.

    Science.gov (United States)

    Kim, Min-Jeong; Kil, Minkwang; Jung, Jong-Hwan; Kim, Jinmi

    2008-02-01

    In the fungal pathogen Candida albicans, the yeast-to-hyphal transition occurs in response to a broad range of environmental stimuli and is considered to be a major virulence factor. To address whether the zinc homeostasis affects the growth or pathogenicity of C. albicans, we functionally characterized the zinc-finger protein Csr1 during filamentation. The deduced amino acid sequence of Csr1 showed a 49% similarity to the zinc-specific transcription factor, Zap1 of Saccharomyces cerevisiae. Sequential disruptions of CSR1 were carried out in diploid C. albicans. The csr1/csr1 mutant strain showed severe growth defects under zinc-limited growth conditions and the filamentation defect under hyphainducing media. The colony morphology and the germ-tube formation were significantly affected by the csr1 mutation. The expression of the hyphae-specific gene HWP1 was also impaired in csr1/csr1 cells. The C. albicans homologs of ZRT1 and ZRT2, which are zinc-transporter genes in S. cerevisiae, were isolated. High-copy number plasmids of these genes suppressed the filamentation defect of the csr1/csr1 mutant strain. We propose that the filamentation phenotype of C. albicans is closely associated with the zinc homeostasis in the cells and that Csr1 plays a critical role in this regulation. PMID:18309267

  7. 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.

  8. 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

  9. 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...

  10. 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

  11. 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...

  12. 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.

  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. 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...

  15. 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...

  16. Candida albicans menengitis in a newborn with classical galactosemia

    Directory of Open Access Journals (Sweden)

    Hüseyin Altunhan

    2012-12-01

    Full Text Available Classical galactosemia is a rarely seen carbohydrate metabolismdisorder. The frequency of sepsis significantlyincreases in patients with galactosemia. The most commonagent causing sepsis is E. coli. Sepsis due to fungusin patients with galactosemia is rarely reported. Candidais an important cause of sepsis in newborn intensive careunits especially in newborns with underlying risk factorssuch as prematurity and low birth weight. Although themost common etiologic agent of sepsis is E. coli in caseswith galactosemia, it should be kept in mind that candidamay also be causative agent of sepsis and meningitis inthese patients even though there is no underlying risk factor.Also the clinical and laboratory findings of candidiasismay be obscure. For this reason, especially in newborncandida meningitis, the index of suspicion should be kepthigh for early diagnosis and treatment. In such patientscerebrospinal fluid analysis, culture and brain imagingshould be done necessarily, because early diagnosis andtreatment will be life saving. In this article we reported agalactosemia case with the diagnosis of meningitis andCandida albicans grown in his blood culture derived onthe fourth day of admission to clinic.Key words: Candida albicans, galactosemia, meningitis,newborn, sepsis

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. MOLECULAR TYPING OF Candida albicans ISOLATES FROM HOSPITALIZED PATIENTS

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    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.

  2. In vivo Models for Candida Albicans Biofilms Study

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    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.

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

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    Mohamed Ahariz

    2010-08-01

    Full Text Available Mohamed Ahariz1, Philippe Courtois1,21Laboratory of Experimental Hormonology, Université Libre de Bruxelles, Brussels, 2UER de Biologie Médicale, Haute Ecole Francisco Ferrer, Brussels, BelgiumAbstract: The present study aimed to document Candida albicans biofilm development on titanium and its modulation by a peroxidase-precoated material which can generate antimicrobials, such as hypoiodite or hypothiocyanite, from hydrogen peroxide, iodide, or thiocyanate. For this purpose, titanium (powder or foil was suspended in Sabouraud liquid medium inoculated with C. albicans ATCC10231. After continuous stirring for 2–21 days at room temperature, the supernatant was monitored by turbidimetry at 600 nm and titanium washed three times in sterile Sabouraud broth. Using the tetrazolium salt MTT-formazan assay, the titanium-adherent fungal biomass was measured as 7.50 ± 0.60 × 106 blastoconidia per gram of titanium powder (n = 30 and 0.50 ± 0.04 × 106 blastoconidia per cm² of titanium foil (n = 12. The presence of yeast on the surface of titanium was confirmed by microscopy both on fresh preparations and after calcofluor white staining. However, in the presence of peroxidase systems (lactoperoxidase with substrates such as hydrogen peroxide donor, iodide, or thiocyanate, Candida growth in both planktonic and attached phases appeared to be inhibited. Moreover, this study demonstrates the possible partition of peroxidase systems between titanium material (peroxidase-precoated and liquid environment (containing peroxidase substrates to limit C. albicans biofilm formation.Keywords: adhesion, material, oral, yeast

  4. 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.

  5. 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 ...

  6. 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

  7. The adaptive metabolic response involves specific protein glutathionylation during the filamentation process in the pathogen Candida albicans.

    Science.gov (United States)

    Gergondey, R; Garcia, C; Serre, V; Camadro, J M; Auchère, F

    2016-07-01

    Candida albicans is an opportunist pathogen responsible for a large spectrum of infections, from superficial mycosis to the systemic disease candidiasis. Its ability to adopt various morphological forms, such as unicellular yeasts, filamentous pseudohyphae and hyphae, contributes to its ability to survive within the host. It has been suggested that the antioxidant glutathione is involved in the filamentation process. We investigated S-glutathionylation, the reversible binding of glutathione to proteins, and the functional consequences on C. albicans metabolic remodeling during the yeast-to-hyphae transition. Our work provided evidence for the specific glutathionylation of mitochondrial proteins involved in bioenergetics pathways in filamentous forms and a regulation of the main enzyme of the glyoxylate cycle, isocitrate lyase, by glutathionylation. Isocitrate lyase inactivation in the hyphal forms was reversed by glutaredoxin treatment, in agreement with a glutathionylation process, which was confirmed by proteomic data showing the binding of one glutathione molecule to the enzyme (data are available via ProteomeXchange with identifier PXD003685). We also assessed the effect of alternative carbon sources on glutathione levels and isocitrate lyase activity. Changes in nutrient availability led to morphological flexibility and were related to perturbations in glutathione levels and isocitrate lyase activity, confirming the key role of the maintenance of intracellular redox status in the adaptive metabolic strategy of the pathogen. PMID:27083931

  8. 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.

  9. 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

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

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    Sunitha Jagalur Doddanna

    2013-01-01

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

  11. 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.

  12. 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.

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

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    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.

  14. 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.

  15. Candida albicans interface infection after deep anterior lamellar keratoplasty

    Directory of Open Access Journals (Sweden)

    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.

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

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    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.

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

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    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.

  18. The MP65 gene is required for cell wall integrity, adherence to epithelial cells and biofilm formation in Candida albicans

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    Girolamo Antonietta

    2011-05-01

    Full Text Available Abstract Background The MP65 gene of Candida albicans (orf19.1779 encodes a putative β-glucanase mannoprotein of 65 kDa, which plays a main role in a host-fungus relationship, morphogenesis and pathogenicity. In this study, we performed an extensive analysis of a mp65Δ mutant to assess the role of this protein in cell wall integrity, adherence to epithelial cells and biofilm formation. Results The mp65Δ mutant showed a high sensitivity to a range of cell wall-perturbing and degrading agents, especially Congo red, which induced morphological changes such as swelling, clumping and formation of hyphae. The mp65Δ mutant showed an activation of two MAPKs (Mkc1p and Cek1p, a high level of expression of two stress-related genes (DDR48 and SOD5, and a modulated expression of β-glucan epitopes, but no gross changes in cell wall polysaccharide composition. Interestingly, the mp65Δ mutant displayed a marked reduction in adhesion to BEC and Caco-2 cells and severe defects in biofilm formation when compared to the wild type. All of the mentioned properties were totally or partially recovered in a revertant strain, demonstrating the specificity of gene deletion. Conclusions We demonstrate that the MP65 gene of Candida albicans plays a significant role in maintaining cell wall integrity, as well as in adherence to epithelia and biofilm formation, which are major virulence attributes of this fungus.

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

    OpenAIRE

    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...

  20. 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...

  1. 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...

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

    Science.gov (United States)

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

    2012-04-01

    Oral candidiasis is often accompanied by severe inflammation, resulting in a decline in the quality of life of immunosuppressed individuals and elderly people. To develop a new oral therapeutic option for candidiasis, a nonpathogenic commensal oral probiotic microorganism, Streptococcus salivarius K12, was evaluated for its ability to modulate Candida albicans growth in vitro, and its therapeutic activity in an experimental oral candidiasis model was tested. In vitro inhibition of mycelial growth of C. albicans was determined by plate assay and fluorescence microscopy. Addition of S. salivarius K12 to modified RPMI 1640 culture medium inhibited the adherence of C. albicans to the plastic petri dish in a dose-dependent manner. Preculture of S. salivarius K12 potentiated its inhibitory activity for adherence of C. albicans. Interestingly, S. salivarius K12 was not directly fungicidal but appeared to inhibit Candida adhesion to the substratum by preferentially binding to hyphae rather than yeast. To determine the potentially anti-infective attributes of S. salivarius K12 in oral candidiasis, the probiotic was administered to mice with orally induced candidiasis. Oral treatment with S. salivarius K12 significantly protected the mice from severe candidiasis. These findings suggest that S. salivarius K12 may inhibit the process of invasion of C. albicans into mucous surfaces or its adhesion to denture acrylic resins by mechanisms not associated with the antimicrobial activity of the bacteriocin. S. salivarius K12 may be useful as a probiotic as a protective tool for oral care, especially with regard to candidiasis. PMID:22267663

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

    Science.gov (United States)

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

    2012-04-01

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

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

    Science.gov (United States)

    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.

  5. 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 ...

  6. 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

  7. 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...

  8. 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.

  9. 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

  10. 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 ...

  11. 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

  12. 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 ...

  13. 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...

  14. 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...

  15. 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.

  16. 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 ...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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.

  2. 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.

  3. 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

  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. Contact-sensing by hyphae of dermatophytic and saprophytic fungi.

    Science.gov (United States)

    Perera, T H; Gregory, D W; Marshall, D; Gow, N A

    1997-01-01

    Contact-sensing or thigmotropism is the directional growth response of cells in relation to topographical guidance cues. Thigmotropism is thought to play a major role in the location of infectable sites on plants by phytopathogenic fungi and has recently been shown to be a property of hyphae in the human pathogenic fungus Candida albicans. Here we show that hyphae of the dermatophytes Epidermophyton floccosum, Microsporum canis and Trichophyton mentagrophytes reorientate their direction of growth in response to grooves and pores of membrane substrata as did hyphae of the saprophytes Mucor mucedo and Neurospora crassa. This suggests that the thigmotropic behaviour of hyphae is not a specific property of pathogens, but rather a general feature of the growth of fungal hyphae that must forage for nutrients on surfaces and within solid materials.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. The fungus Candida albicans tolerates ambiguity at multiple codons

    Directory of Open Access Journals (Sweden)

    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.

  8. 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

  9. 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.

  10. 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

  11. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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

  14. 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.

  15. 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.

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

    Science.gov (United States)

    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.

  17. 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...

  18. Antifungal susceptibility and molecular typing of 115 Candida albicans isolates obtained from vulvovaginal candidiasis patients in 3 Shanghai maternity hospitals.

    Science.gov (United States)

    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.

  19. 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

  20. 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

  1. 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.

  2. 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

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  5. 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

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

    Directory of Open Access Journals (Sweden)

    Humidah Alanazi

    2014-01-01

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

  7. Cigarette smoke-exposed Candida albicans increased chitin production and modulated human fibroblast cell responses.

    Science.gov (United States)

    Alanazi, Humidah; Semlali, Abdelhabib; Perraud, Laura; Chmielewski, Witold; Zakrzewski, Andrew; Rouabhia, Mahmoud

    2014-01-01

    The predisposition of cigarette smokers for development of respiratory and oral bacterial infections is well documented. Cigarette smoke can also contribute to yeast infection. The aim of this study was to investigate the effect of cigarette smoke condensate (CSC) on C. albicans transition, chitin content, and response to environmental stress and to examine the interaction between CSC-pretreated C. albicans and normal human gingival fibroblasts. Following exposure to CSC, C. albicans transition from blastospore to hyphal form increased. CSC-pretreated yeast cells became significantly (P < 0.01) sensitive to oxidation but significantly (P < 0.01) resistant to both osmotic and heat stress. CSC-pretreated C. albicans expressed high levels of chitin, with 2- to 8-fold recorded under hyphal conditions. CSC-pretreated C. albicans adhered better to the gingival fibroblasts, proliferated almost three times more and adapted into hyphae, while the gingival fibroblasts recorded a significantly (P < 0.01) slow growth rate but a significantly higher level of IL-1β when in contact with CSC-pretreated C. albicans. CSC was thus able to modulate both C. albicans transition through the cell wall chitin content and the interaction between C. albicans and normal human gingival fibroblasts. These findings may be relevant to fungal infections in the oral cavity in smokers. PMID:25302312

  8. 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.

  9. Aft2, a novel transcription regulator, is required for iron metabolism, oxidative stress, surface adhesion and hyphal development in Candida albicans.

    Science.gov (United States)

    Xu, Ning; Cheng, Xinxin; Yu, Qilin; Qian, Kefan; Ding, Xiaohui; Liu, Ruming; Zhang, Biao; Xing, Laijun; Li, Mingchun

    2013-01-01

    Morphological transition and iron metabolism are closely relevant to Candida albicans pathogenicity and virulence. In our previous study, we demonstrated that C. albicans Aft2 plays an important role in ferric reductase activity and virulence. Here, we further explored the roles of C. albicans Aft2 in numerous cellular processes. We found that C. albicans Aft2 exhibited an important role in iron metabolism through bi-directional regulation effects on iron-regulon expression. Deletion of AFT2 reduced cellular iron accumulation under iron-deficient conditions. Furthermore, both reactive oxygen species (ROS) generation and superoxide dismutase (SOD) activity were remarkably increased in the aft2Δ/Δ mutant, which were thought to be responsible for the defective responses to oxidative stress. However, we found that over-expression of C. albicans AFT2 under the regulation of the strong PGK1 promoter could not effectively rescue Saccharomyces cerevisiae aft1Δ mutant defects in some cellular processes, such as cell-wall assembly, ion homeostasis and alkaline resistance, suggesting a possibility that C. albicans Aft2 weakened its functional role of regulating some cellular metabolism during the evolutionary process. Interestingly, deletion of AFT2 in C. albicans increased cell surface hydrophobicity, cell flocculation and the ability of adhesion to polystyrene surfaces. In addition, our results also revealed that C. albicans Aft2 played a dual role in regulating hypha-specific genes under solid and liquid hyphal inducing conditions. Deletion of AFT2 caused an impaired invasive growth in solid medium, but an increased filamentous aggregation and growth in liquid conditions. Moreover, iron deficiency and environmental cues induced nuclear import of Aft2, providing additional evidence for the roles of Aft2 in transcriptional regulation. PMID:23626810

  10. 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.

  11. 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...

  12. 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 ...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  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. 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...

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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...

  10. 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...

  11. Presumptive identification of Candida species other than C. albicans, C. krusei, and C. tropicalis with the chromogenic medium CHROMagar Candida

    Directory of Open Access Journals (Sweden)

    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.

  12. 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...

  13. 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

  14. Anti-fungal activity of Morinda citrifolia (noni extracts against Candida albicans: An in vitro study

    Directory of Open Access Journals (Sweden)

    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.

  15. 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.

  16. 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.

  17. 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

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

    Science.gov (United States)

    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).

  19. 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.

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

    Science.gov (United States)

    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.

  1. 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.

  2. 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.)

  3. 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.)

  4. 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

  5. 氯生太尔体外抗白念珠菌活性的研究%In vitro antifungal activity of closantel against Candida albicans

    Institute of Scientific and Technical Information of China (English)

    陈文峰; 张子平; 程波

    2012-01-01

    目的 研究氯生太尔体外抗白念珠菌的活性.方法 用微量稀释法测定氟康唑单独及联合氯生太尔对白念珠菌标准株CAF-2的最小抑菌浓度(MIC);用含10%小牛血清的RPMI 1640液体培养基诱导菌丝形成,计算并比较实验组(氯生太尔作用后)和对照组(未加氯生太尔)10株白念珠菌菌丝的形成率;用透射及扫描电镜观察白念珠菌标准株CAF-2在氯生太尔作用后的超微结构变化.结果 氯生太尔在体外能抑制白念珠菌的生长,且与氟康唑联合用药时可以明显提高氟康唑对白念珠菌的敏感性.氯生太尔对白念珠菌的菌丝形成抑制实验,对照组见大量菌丝形成,菌丝形成率为91.2%±3.9%,氯生太尔实验组菌丝形成率为29.8%±5.1%,实验组菌丝形成率明显降低,差异有统计学意义(t=30.24,P< 0.05).透射电镜观察氯生太尔作用后的白念珠菌,细胞呈圆形、椭圆形或多形性,细胞表面出芽不规则,细胞壁外层的电子致密层分布不均匀,部分有缺失,透明层厚薄不一,部分细胞膜塌陷,局部破坏,胞内空泡增多;扫描电镜观察,氯生太尔作用后的白念珠菌,表面凹凸不平,出芽细胞少且出芽不规则.结论 氯生太尔在体外具有明显的抗白念珠菌活性.%Objective To determine the in vitro antifungal effects of closantel against Candida albicans.Methods A microdilution method was used to determine the minimum inhibitory concentration (MIC)of fluconazole alone and in combination with closantel against Candida albicans standard strain CAF-2.Ten strains of Candida albicans were cultured in RPMI-1640 liquid culture containing 10% calf serum with or without the presence of closantel at 16 mg/L,followed by the observation of hypha formation.Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) were performed to observe the ultrastructure of Candida albicans CAF-2 strain after exposure to closantel at 16 mg

  6. 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.

  7. 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.

  8. 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.

  9. 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...

  10. 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

  11. 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

  12. 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.``

  13. 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

  14. 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

  15. 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.

  16. Antifungal activity of silver nanoparticles in combination with nystatin and chlorhexidine digluconate against Candida albicans and Candida glabrata biofilms.

    Science.gov (United States)

    Monteiro, Douglas R; Silva, Sónia; Negri, Melyssa; Gorup, Luiz F; de Camargo, Emerson R; Oliveira, Rosário; Barbosa, Debora B; Henriques, Mariana

    2013-11-01

    Although silver nanoparticles (SN) have been investigated as an alternative to conventional antifungal drugs in the control of Candida-associated denture stomatitis, the antifungal activity of SN in combination with antifungal drugs against Candida biofilms remains unknown. Therefore, the aim of this study was to evaluate the antifungal efficacy of SN in combination with nystatin (NYT) or chlorhexidine digluconate (CHG) against Candida albicans and Candida glabrata biofilms. The drugs alone or combined with SN were applied on mature Candida biofilms (48 h), and after 24 h of treatment their antibiofilm activities were assessed by total biomass quantification (by crystal violet staining) and colony forming units enumeration. The structure of Candida biofilms was analysed by scanning electron microscopy (SEM) images. The data indicated that SN combined with either NYT or CHG demonstrated synergistic antibiofilm activity, and this activity was dependent on the species and on the drug concentrations used. SEM images showed that some drug combinations were able to disrupt Candida biofilms. The results of this study suggest that the combination of SN with NYT or CHG may have clinical implications in the treatment of denture stomatitis. However, further studies are needed before recommending the use of these drugs safely in clinical situations. PMID:23773119

  17. Candida albicans adherence on acrylic resin plates immersed in black tea steeping

    Directory of Open Access Journals (Sweden)

    Soebagio Soebagio

    2010-12-01

    Full Text Available Background: Black tea or Cournelia sinensis is one of known tea varieties in Indonesia. Actually, black tea is consumed daily as beverage that can function as antiseptics and fungicides. Black tea containing antibacterial and fungicide properties can reduce the number of Candida albicans (C. albicans colony attachment on the surface of acrylic resin plates. Purpose: This study was done to determine the effective concentration of black tea steeping used as the immersion material of acrylic resin plates towards the number of Candida albicans colonies. Methods: In this study, acrylic resin plates with the size of 10 × 20 × 1 mm were immersed in black tea steeping with the following concentrations, 3.33%, 6.66%, and 13.33%, for one hour. The growth of C. albicans colonies were then detected by counting the number of colonies growing on Sabouraud’s dextrose medium. Data was analyzed by using both One-Way ANOVA with the significance level of 5%, and Tuckey’s multiple comparison tests (Tuckey’s HSD test. Results: There were significant differences in the number of C. albicans colonies in acrylic resin plates immersed in black tea with the concentration of 3.33%, 6.66%, and 13.33%. Conclusion: It can be concluded that the higher concentration of black tea (13.33% used to immerse acrylic resin plates, the greater the decreased number of C. albicans colonies.Latar belakang: Teh hitam atau Cournelia sinensis adalah salah satu macam teh yang dikenal di Indonesia. Teh hitam seringkali dipakai sebagai minuman sehari- hari dan berkhasiat sebagai antiseptik maupun fungisid. Teh hitam yang mengandung sifat antibakteri dan fungisid dapat menurunkan jumlah koloni Candida albicans (C. albicans yang melekat pada permukaan lempeng resin akrilik. Tujuan: Untuk mengetahui konsentrasi efektif seduhan teh hitam sebagai bahan perendam lempeng resin akrilik terhadap jumlah koloni C. albicans. Metode: Pada penelitian ini lempeng resin akrilik ukuran 10 × 20 × 1 mm

  18. Antifungal Activity of Coumarin from Ageratum conyzoides L. Leaves on Candida albicans cells

    Directory of Open Access Journals (Sweden)

    Gunawan Pamudji Widodo

    2012-07-01

    Full Text Available The aim of this study was to identify the antifungal activity of coumarin isolated from Ageratum conyzoides L. leaves and to observe its influence on Candida albicans cells by scanning electron microscope (SEM and transmission electron microscope (TEM. Antifungal activity testing by disk diffusion method showed coumarin was active toward pathogenic fungus, Candida albicans with the MIC value of coumarin of 125 g mL-1. The influence of this substance on C. albicans cells was observed by scanning and transmission electron microscopies. The result showed that this compound damaged the cell by pores formation on the cell wall. The death of cells occurred due to leakage and necrotic of cytoplasmic content.

  19. 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

    Directory of Open Access Journals (Sweden)

    C. Hanny Wijaya1*

    2014-12-01

    Full Text Available 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 biofilms formation by using in vitro biofilm assay and viability assay. Furthermore, the influence of concentration of cajuput oil on the anti-microbial activities had been analyzed. All the tested concentration of cajuput oil in cajuputs candy was effective to inhibit the viability of C. albicans. The provision of flavor components of cajuput and peppermint oil could produce synergistic effects compared to a single flavor component. The addition of cajuput oil at 0.6% was able to inhibit the viability of C. albicans. The activities of the cajuput oil showed positive correlation to the concentration. The variable of plus and minus 0.1% addition of the cajuput oil concentration, however, produced no significant difference to inhibit the growth of C. albicans in biofilm. Sensory test, hedonic test, was conducted to evaluate the flavor, aroma, and overall attributes, resulting in no significant difference between 0.6 to 0.8% additions of cajuput oil upon the sensory acceptance.

  20. An evaluation on the adherence of Candida albicans to different denture- base materials

    Directory of Open Access Journals (Sweden)

    Savabi O

    2004-02-01

    Full Text Available The surface topography of denture base material is an important factor for the"nadhesion of Candida albicans and other microorganisms."nPurpose: The aim of this study was to evaluate the adherence of Candida albicans to four types of denture"nbase materials (Acropars acrylic resin, Meliodent acrylic resin, rough and smooth surfaces of Molloplast B."nMaterials and Methods: Seven blocks of two types of acrylic resins and ten blocks of silicone with one"nrough and one smooth surface were made and incubated in a suspension of Candida albicans. After washing,"nthe blocks were stained with acridine orange and examined under fluorescent microscope. For statistical"nanalysis ANOVA and Duncan tests were used."nResults: It was observed that Candida adhesion to rough surfaces of acrylic resins and silicone was"nsignificantly more than polished surfaces of acrylic resins and smooth silicone (PO.0001. However, no"nstatistical significant difference was found between polished acrylic resins surfaces and smooth silicone."nConclusion: Significant differences in the adherence of Candida to the surfaces of different denture base"nmaterials are due to differences in surface topography, chemical, physical and hydrophobic properties so it is"nrecommended to minimize the roughness and irregularities of denture base.

  1. A single nucleotide polymorphism uncovers a novel function for the transcription factor Ace2 during Candida albicans hyphal development.

    Directory of Open Access Journals (Sweden)

    Diana M Calderón-Noreña

    2015-04-01

    Full Text Available Candida albicans is a major invasive fungal pathogen in humans. An important virulence factor is its ability to switch between the yeast and hyphal forms, and these filamentous forms are important in tissue penetration and invasion. A common feature for filamentous growth is the ability to inhibit cell separation after cytokinesis, although it is poorly understood how this process is regulated developmentally. In C. albicans, the formation of filaments during hyphal growth requires changes in septin ring dynamics. In this work, we studied the functional relationship between septins and the transcription factor Ace2, which controls the expression of enzymes that catalyze septum degradation. We found that alternative translation initiation produces two Ace2 isoforms. While full-length Ace2, Ace2L, influences septin dynamics in a transcription-independent manner in hyphal cells but not in yeast cells, the use of methionine-55 as the initiation codon gives rise to Ace2S, which functions as the nuclear transcription factor required for the expression of cell separation genes. Genetic evidence indicates that Ace2L influences the incorporation of the Sep7 septin to hyphal septin rings in order to avoid inappropriate activation of cell separation during filamentous growth. Interestingly, a natural single nucleotide polymorphism (SNP present in the C. albicans WO-1 background and other C. albicans commensal and clinical isolates generates a stop codon in the ninth codon of Ace2L that mimics the phenotype of cells lacking Ace2L. Finally, we report that Ace2L and Ace2S interact with the NDR kinase Cbk1 and that impairing activity of this kinase results in a defect in septin dynamics similar to that of hyphal cells lacking Ace2L. Together, our findings identify Ace2L and the NDR kinase Cbk1 as new elements of the signaling system that modify septin ring dynamics in hyphae to allow cell-chain formation, a feature that appears to have evolved in specific C

  2. 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.

  3. The proteolytic potential of Candida albicans in human saliva supplemented with glucose.

    Science.gov (United States)

    Samaranayake, L P; Hughes, A; MacFarlane, T W

    1984-02-01

    The production of proteases by Candida albicans in batch cultures of human saliva supplemented with glucose was investigated with two clinical strains of Candida and both individual and pooled samples of whole saliva from volunteers. Salivary proteolysis during a 48-h period was estimated by biochemical and isoelectric focusing techniques. Candidal growth in saliva was associated with acid production and salivary proteolysis and there was a highly significant positive correlation between these two activities. Neither candidal growth nor proteolysis was observed in glucose-free control samples and with one strain of Candida cultured in the saliva of one individual. Isotachophoretic analysis of culture liquor showed a significant increase in acetate and pyruvate ions. The oral cavity provides niches that have a low pH and are periodically supplemented with dietary carbohydrates. The acidic proteases of C. albicans may play a role in the pathogenesis of oral candidoses. PMID:6363704

  4. Diversities of interaction of murine macrophages with three strains of Candida albicans represented by MyD88, CARD9 gene expressions and ROS, IL-10 and TNF-α secretion

    OpenAIRE

    Zhang, Xiaohuan; Ge, Yanping; Li, Wenqing; Hu, Yan

    2014-01-01

    Aim: To explore the mechanisms underlying the different responses of macrophages to distinct Candida albicans strains. Methods: Bone marrow was collected from mice. Macrophages were independently incubated with 3 Candida albicans strains. Results: MyD88 expression in Candida albicans 3683 group was significantly higher than that in Candida albicans 3630 group and Candida albicans SC5314 group, and marked difference was also observed between later two groups (P

  5. The expression of genes involved in the ergosterol biosynthesis pathway in Candida albicans and Candida dubliniensis biofilms exposed to fluconazole.

    LENUS (Irish Health Repository)

    2009-03-01

    The expression of the ERG1, ERG3, ERG7, ERG9, ERG11 and ERG25 genes in response to incubation with fluconazole and biofilm formation was investigated using reverse-transcription PCR and real-time PCR in Candida albicans and Candida dubliniensis clinical isolates. The viability of biofilm was measured using an 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction assay and confocal scanning laser microscopy (CSLM). Expression of the ERG11 gene was found to be low or moderate and it was regulated by fluconazole addition more so than by biofilm formation. Very low or non-detectable expression of ERG1, ERG7 and ERG25 genes was detected in C. albicans. The expression of the ERG9 increased in the presence of fluconazole in some isolates. Following incubation with fluconazole, formation of biofilm by C. dubliniensis was coupled with up-regulation of the ERG3 and ERG25 genes as have been observed previously in C. albicans. Planktonic cells of both Candida species released from biofilm displayed similar resistance mechanisms to fluconazole like attached cells. The XTT reduction assay and CSLM revealed that although incubation with fluconazole decreased the biofilm thickness, these were still comprised metabolically active cells able to disseminate and produce biofilm. Our data indicate that biofilm represents a highly adapted community reflecting the individuality of clinical isolates.

  6. 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

  7. 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

  8. Modulation of phagosomal pH by Candida albicans promotes hyphal morphogenesis and requires Stp2p, a regulator of amino acid transport.

    Science.gov (United States)

    Vylkova, Slavena; Lorenz, Michael C

    2014-03-01

    Candida albicans, the most important fungal pathogen of humans, has a unique interaction with macrophages in which phagocytosis induces a switch from the yeast to hyphal form, allowing it to escape by rupturing the immune cell. While a variety of factors induce this switch in vitro, including neutral pH, it is not clear what triggers morphogenesis within the macrophage where the acidic environment should inhibit this transition. In vitro, C. albicans grown in similar conditions in which amino acids are the primary carbon source generate large quantities of ammonia to raise the extracellular pH and induce the hyphal switch. We show here that C. albicans cells neutralize the macrophage phagosome and that neutral pH is a key inducer of germination in phagocytosed cells by using a mutant lacking STP2, a transcription factor that regulates the expression of multiple amino acid permeases, that is completely deficient in alkalinization in vitro. Phagocytosed stp2Δ mutant cells showed significant reduction in hypha formation and escaped from macrophages less readily compared to wild type cells; as a result stp2Δ mutant cells were killed at a higher rate and caused less damage to RAW264.7 macrophages. Stp2p-regulated import leads to alkalinization of the phagosome, since the majority of the wild type cells fail to co-localize with acidophilic dyes, whereas the stp2Δ mutant cells were located in acidic phagosomes. Furthermore, stp2Δ mutant cells were able to form hyphae and escape from neutral phagosomes, indicating that the survival defect in these cells was pH dependent. Finally, these defects are reflected in an attenuation of virulence in a mouse model of disseminated candidiasis. Altogether our results suggest that C. albicans utilizes amino acids to promote neutralization of the phagosomal pH, hyphal morphogenesis, and escape from macrophages. PMID:24626429

  9. Modulation of phagosomal pH by Candida albicans promotes hyphal morphogenesis and requires Stp2p, a regulator of amino acid transport.

    Directory of Open Access Journals (Sweden)

    Slavena Vylkova

    2014-03-01

    Full Text Available Candida albicans, the most important fungal pathogen of humans, has a unique interaction with macrophages in which phagocytosis induces a switch from the yeast to hyphal form, allowing it to escape by rupturing the immune cell. While a variety of factors induce this switch in vitro, including neutral pH, it is not clear what triggers morphogenesis within the macrophage where the acidic environment should inhibit this transition. In vitro, C. albicans grown in similar conditions in which amino acids are the primary carbon source generate large quantities of ammonia to raise the extracellular pH and induce the hyphal switch. We show here that C. albicans cells neutralize the macrophage phagosome and that neutral pH is a key inducer of germination in phagocytosed cells by using a mutant lacking STP2, a transcription factor that regulates the expression of multiple amino acid permeases, that is completely deficient in alkalinization in vitro. Phagocytosed stp2Δ mutant cells showed significant reduction in hypha formation and escaped from macrophages less readily compared to wild type cells; as a result stp2Δ mutant cells were killed at a higher rate and caused less damage to RAW264.7 macrophages. Stp2p-regulated import leads to alkalinization of the phagosome, since the majority of the wild type cells fail to co-localize with acidophilic dyes, whereas the stp2Δ mutant cells were located in acidic phagosomes. Furthermore, stp2Δ mutant cells were able to form hyphae and escape from neutral phagosomes, indicating that the survival defect in these cells was pH dependent. Finally, these defects are reflected in an attenuation of virulence in a mouse model of disseminated candidiasis. Altogether our results suggest that C. albicans utilizes amino acids to promote neutralization of the phagosomal pH, hyphal morphogenesis, and escape from macrophages.

  10. 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

  11. 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 ...

  12. [Demonstration of β-1,2 mannan structures expressed on the cell wall of Candida albicans yeast form but not on the hyphal form by using monoclonal antibodies].

    Science.gov (United States)

    Aydın, Cevahir; Ataoğlu, Haluk

    2015-01-01

    Candida albicans is a polymorphic fungus that may be observed as both commensal and opportunistic pathogen in humans. As one of the major components of Candida cell wall structure, mannan plays an important role in the fungus-host cell interaction and in virulence. The ability to switch from yeast to hypha form of microorganism is crutial in the development of C.albicans infections. Hyphal form has different antigenic properties compared to yeast form and structural changes occur in the yeast cell wall during transition from yeast to hypha form. Although there are several factors associated with this transition process, sufficient information is not available. The aim of this study was to investigate the change of configuration in mannan structure found in C.albicans cell wall by using monoclonal antibodies. C.albicans (NIHA 207) serotype A strains were used as test strains throughout the study, together with Salmonella choleraesuis 211 and Salmonella infantis as controls with similar cell wall structures to that of C.albicans. Cultures were maintained on YPD-agar medium by incubating at 28°C for yeast forms, and on YPD-broth medium in a shaking incubator at 37°C for 3-4 hours for the growth of hyphal forms. Cells were harvested in the exponential phase, and after being washed, the mannan content from C.albicans were extracted from pellet by heating in 20 mM sodium citrate buffer for 90 minutes at 125°C. Hybridoma technique was used for the production of monoclonal antibodies. After immunizing the Balb/C mice with antigen, the splenocytes were harvested and fusion was performed between spleen cells and F0 myeloma cells. The clones grown in HAT medium were screened for the presence of antibody producing hybrid cells by ELISA method. The antibody isotypes were determined by using a commercial kit (Pierce Biotechnology, ABD). The culture supernatants which contained monoclonal antibodies were collected and purified according to the ammonium sulphate method

  13. Impact of oxidative and osmotic stresses on Candida albicans biofilm formation.

    Science.gov (United States)

    Pemmaraju, Suma C; Padmapriya, Kumar; Pruthi, Parul A; Prasad, R; Pruthi, Vikas

    2016-09-01

    Candida albicans possesses an ability to grow under different host-driven stress conditions by developing robust protective mechanisms. In this investigation the focus was on the impact of osmotic (2M NaCl) and oxidative (5 mM H2O2) stress conditions during C. albicans biofilm formation. Oxidative stress enhanced extracellular DNA secretion into the biofilm matrix, increased the chitin level, and reduced virulence factors, namely phospholipase and proteinase activity, while osmotic stress mainly increased extracellular proteinase and decreased phospholipase activity. Fourier transform infrared and nuclear magnetic resonance spectroscopy analysis of mannan isolated from the C. albicans biofilm cell wall revealed a decrease in mannan content and reduced β-linked mannose moieties under stress conditions. The results demonstrate that C. albicans adapts to oxidative and osmotic stress conditions by inducing biofilm formation with a rich exopolymeric matrix, modulating virulence factors as well as the cell wall composition for its survival in different host niches. PMID:27472386

  14. 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

  15. Additive potential of ginger starch on antifungal potency of honey against Candida albicans

    Institute of Scientific and Technical Information of China (English)

    Ahmed Moussa; Djebli Noureddine; Hammoudi SM; Aissat Saad; Akila Bourabeh; Hemida Houari

    2012-01-01

    Objective: To evaluate the additive action of ginger starch on the antifungal activity of honey against Candida albicans (C. albicans). Methods: C. albicans was used to determine the minimum inhibitory concentration (MIC) of four varieties of Algerian honey. Lower concentrations of honey than the MIC were incubated with a set of concentrations of starch and then added to media to determine the minimum additive inhibitory concentration (MAIC). Results: The MIC for the four varieties of honey without starch against C. albicans ranged between 38% and 42% (v/v). When starch was incubated with honey and then added to media, a MIC drop was noticed with each variety. MAIC of the four varieties ranged between 32% honey (v/v) with 4% starch and 36% honey (v/v) with 2% starch. Conclusions: The use of ginger starch allows honey benefit and will constitute an alternative way against the resistance to antifungal agents.

  16. Biochemical characterization of recombinant dihydroorotate dehydrogenase from the opportunistic pathogenic yeast Candida albicans

    DEFF Research Database (Denmark)

    Zameitat, E.; Gojkovic, Zoran; Knecht, Wolfgang;

    2006-01-01

    Candida albicans is the most prevalent yeast pathogen in humans, and recently it has become increasingly resistant to the current antifungal agents. In this study we investigated C. albicans dihydroorotate dehydrogenase (DHODH, EC 1.3.99.11), which catalyzes the fourth step of de novo pyrimidine...... lacks the targeting sequence and the transmembrane domain, were subcloned from C. albicans, recombinantly expressed in Escherichia coli, purified, and characterized for their kinetics and substrate specificity. An inhibitor screening with 28 selected compounds was performed. Only the dianisidine...... derivative, redoxal, and the biphenyl quinoline-carboxylic acid derivative, brequinar sodium, which are known to be potent inhibitors of mammalian DHODH, markedly reduced C. albicans DHODH activity. This study provides a background for the development of antipyrimidines with high efficacy for decreasing...

  17. Molecular typing of Candida albicans strains isolated from nosocomial candidemia Tipificação molecular de espécies de Candida albicans isoladas de candidemia hospitalar

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    Maria Luiza Moretti Branchini

    1995-12-01

    Full Text Available Yeasts of the genus Candida have been recognized as important microorganisms responsible for nosocomial fungemia. Six blood-stream and two intravenous central catheter C. albicans strains were isolated from eight patients and studied by electrophoretic karyotyping of chromosomal DNA by pulsed-field gel electrophoresis. Seven chromosomal DNA profiles were identified. Two patients showed isolates with the same profile, suggesting nosocomial transmission. Karyotyping of C. albicans revealed an excellent discriminatory power among the isolates and may therefore be useful in the study of nosocomial candidemia.Leveduras do gênero Candida têm sido reconhecidas como importantes causadoras de fungemias hospitalares. Foram estudados os DNA cromossômicos de oito cepas de C. albicans, obtidas de oito pacientes com fungemia hospitalar, por cariotipagem eletroforética através de "pulsed-field gel electrophoresis". As cepas foram obtidas pelo isolamento da levedura em seis hemoculturas e duas infecções relacionadas ao uso de cateter intra-venoso central. Foram identificados sete perfis de DNA cromossômico. Dois pacientes mostraram cepas com o mesmo perfil de DNA sugerindo transmissão nosocomial. A cariotipagem eletroforética revelou excelente capacidade discriminatória entre os isolados sendo útil no estudo das candidemias hospitalares.

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. 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

  3. Modulation of Candida albicans virulence by bacterial biofilms on titanium surfaces.

    Science.gov (United States)

    Cavalcanti, Yuri Wanderley; Wilson, Melanie; Lewis, Michael; Del-Bel-Cury, Altair Antoninha; da Silva, Wander José; Williams, David W

    2016-01-01

    Whilst Candida albicans occurs in peri-implant biofilms, its role in peri-implantitis remains unclear. This study therefore examined the virulence of C. albicans in mixed-species biofilms on titanium surfaces. Biofilms of C. albicans (Ca), C. albicans with streptococci (Streptococcus sanguinis, S. mutans) (Ca-Ss-Sm) and those incorporating Porphyromonas gingivalis (Ca-Pg and Ca-Ss-Sm-Pg) were developed. Expression of C. albicans genes associated with adhesion (ALS1, ALS3, HWP1) and hydrolytic enzymes (SAP2, SAP4, SAP6, PLD1) was measured and hyphal production by C. albicans quantified. Compared with Ca biofilms, significant (pbiofilms containing streptococci (Ca-Ss-Sm). In Ca-Pg biofilms, down-regulation of HWP1 and SAP4 expression, with reduced hyphal production occurred. Ca-Ss-Sm-Pg biofilms had increased hyphal proportions and up-regulation of ALS3, SAP2 and SAP6. In conclusion, C. albicans expressed virulence factors in biofilms that could contribute to peri-implantitis, but this was dependent on associated bacterial species.

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

    Institute of Scientific and Technical Information of China (English)

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

    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 number of colony forming units and for the percentage of viable C. albicans using fluorescence microscopy. First, the antimicrobial activity of calcium hydroxide and the 2% chlorhexidine gel was evaluated by counting the number of colony forming units. After 14 days of intracanal medication, there was a significant decrease in the number of C. albicanscolony forming units at a depth of 0-100 lzm with chlorhexidine treatment either with or without calcium hydroxide compared with the calcium hydroxide only treatment. However, there were no differences in the number of colony forming units at the 100-200 μm depth for any of the medications investigated. C. albicans viability was also evaluated by vital staining techniques and fluorescence microscopy analysis. Antifungal activity against C. albicans significantly increased at both depths in the chlorhexidine groups with and without calcium hydroxide compared with the groups treated with calcium hydroxide only. Treatments with only chlorhexidine or chlorhexidine in combination with calcium hydroxide were effective for elimination of C. albicans.

  5. Candida albicans Amphotericin B-Tolerant Persister Formation is Closely Related to Surface Adhesion.

    Science.gov (United States)

    Sun, Jing; Li, Zhigang; Chu, Haoyue; Guo, Jing; Jiang, Guangshui; Qi, Qingguo

    2016-02-01

    Candida albicans persisters have so far been observed only in biofilm environment; the biofilm element(s) that trigger(s) persister formation are still unknown. In this study, we tried to further elucidate the possible relationship between C. albicans persisters and the early phases of biofilm formation, especially the surface adhesion phase. Three C. albicans strains were surveyed for the formation of persisters. We tested C. albicans persister formation dynamically at different time points during the process of adhesion and biofilm formation. The number of persister cells was determined based on an assessment of cell viability after amphotericin B treatment and colony-forming unit assay. None of the planktonic cultures contained persisters. Immediately following adhesion of C. albicans cells to the surface, persister cells emerged and the proportion of persisters reached a peak of 0.2-0.69 % in approximately 2-h biofilm. As the biofilm matured, the proportion of persisters decreased and was only 0.01-0.02 % by 24 h, while the number of persisters remained stable with no significant change. Persisters were not detected in the absence of an attachment surface which was pre-coated. Persisters were also absent in biofilms that were scraped to disrupt surface adhesion prior to amphotericin B treatment. These results indicate that C. albicans antifungal-tolerant persisters are produced mainly in surface adhesion phase and surface adhesion is required for the emergence and maintenance of C. albicans persisters.

  6. Presence of extracellular DNA in the Candida albicans biofilm matrix and its contribution to biofilms.

    Science.gov (United States)

    Martins, Margarida; Uppuluri, Priya; Thomas, Derek P; Cleary, Ian A; Henriques, Mariana; Lopez-Ribot, José L; Oliveira, Rosário

    2010-05-01

    DNA has been described as a structural component of the extracellular matrix (ECM) in bacterial biofilms. In Candida albicans, there is a scarce knowledge concerning the contribution of extracellular DNA (eDNA) to biofilm matrix and overall structure. This work examined the presence and quantified the amount of eDNA in C. albicans biofilm ECM and the effect of DNase treatment and the addition of exogenous DNA on C. albicans biofilm development as indicators of a role for eDNA in biofilm development. We were able to detect the accumulation of eDNA in biofilm ECM extracted from C. albicans biofilms formed under conditions of flow, although the quantity of eDNA detected differed according to growth conditions, in particular with regards to the medium used to grow the biofilms. Experiments with C. albicans biofilms formed statically using a microtiter plate model indicated that the addition of exogenous DNA (>160 ng/ml) increases biofilm biomass and, conversely, DNase treatment (>0.03 mg/ml) decreases biofilm biomass at later time points of biofilm development. We present evidence for the role of eDNA in C. albicans biofilm structure and formation, consistent with eDNA being a key element of the ECM in mature C. albicans biofilms and playing a predominant role in biofilm structural integrity and maintenance.

  7. Prevalence and antifungal susceptibility of Candida albicans and its related species Candida dubliniensis and Candida africana isolated from vulvovaginal samples in a hospital of Argentina.

    Science.gov (United States)

    Theill, Laura; Dudiuk, Catiana; Morano, Susana; Gamarra, Soledad; Nardin, María Elena; Méndez, Emilce; Garcia-Effron, Guillermo

    2016-01-01

    Candida africana taxonomical status is controversial. It was proposed as a separate species within the Candida albicans species complex; however, phylogenetic analyses suggested that it is an unusual variety of C. albicans. The prevalence of C. albicans-related species (Candida dubliniensis and C. africana) as vulvovaginal pathogens is not known in Argentina. Moreover, data on antifungal susceptibility of isolates causing vulvovaginal candidiasis is scarce. The aims of this study were to establish the prevalence of C. dubliniensis and C. africana in vaginal samples and to evaluate the antifungal susceptibilities of vaginal C. albicans species complex strains. We used a molecular-based method coupled with a new pooled DNA extraction methodology to differentiate C. dubliniensis and C. africana in a collection of 287 strains originally identified as C. albicans isolated from an Argentinian hospital during 2013. Antifungal susceptibilities to fluconazole, clotrimazole, itraconazole, voriconazole, nystatin, amphotericin B and terbinafine were evaluated by using the CLSI M27-A3 and M27-S4 documents. Of the 287 isolates, 4 C. dubliniensis and one C. africana strains (1.39% and 0.35% prevalence, respectively) were identified. This is the first description of C. africana in Argentina and its identification was confirmed by sequencing the ITS2 region and the hwp1 gene. C. dubliniensis and C. africana strains showed very low MIC values for all the tested antifungals. Fluconazole-reduced-susceptibility and azole cross-resistance were observed in 3.55% and 1.41% of the C. albicans isolates, respectively. These results demonstrate that antifungal resistance is still a rare phenomenon in this kind of isolates.

  8. Candida albicans modulates host defense by biosynthesizing the pro-resolving mediator resolvin E1.

    Directory of Open Access Journals (Sweden)

    Eric J Haas-Stapleton

    Full Text Available Candida albicans is an opportunistic fungal pathogen of humans that resides commensally on epithelial surfaces, but can cause inflammation when pathogenic. Resolvins are a class of anti-inflammatory lipids derived from omega-3 polyunsaturated fatty acids (PUFA that attenuate neutrophil migration during the resolution phase of inflammation. In this report we demonstrate that C. albicans biosynthesizes resolvins that are chemically identical to those produced by human cells. In contrast to the trans-cellular biosynthesis of human Resolvin E1 (RvE1, RvE1 biosynthesis in C. albicans occurs in the absence of other cellular partners. C. albicans biosynthesis of RvE1 is sensitive to lipoxygenase and cytochrome P450 monoxygenase inhibitors. We show that 10nM RvE1 reduces neutrophil chemotaxis in response to IL-8; 1nM RvE1 enhanced phagocytosis of Candida by human neutrophils, as well as intracellular ROS generation and killing, while having no direct affect on neutrophil motility. In a mouse model of systemic candidiasis, RvE1 stimulated clearance of the fungus from circulating blood. These results reveal an inter-species chemical signaling system that modulates host immune functions and may play a role in balancing host carriage of commensal and pathogenic C. albicans.

  9. ERG11 mutations associated with azole resistance in Candida albicans isolates from vulvovaginal candidosis patients

    Institute of Scientific and Technical Information of China (English)

    Bin Wang; Li-Hua Huang; Ji-Xue Zhao; Man Wei; Hua Fang; Dan-Yang Wang; Hong-Fa Wang; Ji-Gang Yin; Mei Xiang

    2015-01-01

    Objective:To investigate the azole susceptibility of Candida albicans (C. albicans) from vulvovaginal candidosis patients and to analyze the relationship between ERG11 gene mutations in these isolates and azole resistance. Methods:Three hundred and two clinical isolates of Candida species were collected. Azole susceptibility was tested in vitro in microdilution studies. The ERG11 genes of 17 isolates of C. albicans (2 susceptibles, 5 dose-dependent resistants and 10 resistants) were amplified and sequenced. Results:Of the 302 isolates collected, 70.2%were C. albicans, of which 8.5%, 3.8%and 4.2%were resistant to fluconazole, itraconazole and voriconazole, respectively. In total, 27 missense mutations were detected in ERG11 genes from resistant/susceptible dose-dependent isolates. Among them, Y132H, A114S, and Y257H substitutions were most prevalent and were known to cause fluconazole resistance. G464S and F72S also has been proved to cause fluconazole resistance. Two novel substitutions (T285A, S457P) in hotspot regions were identified. Conclusions:Twenty seven mutations in the ERG11 gene were identified in azole-resistant C. albicans isolates, which indicated a possible relation with the increase in resistance to azole drugs and the recurrence of vulvovaginal candidosis. The relationship of two novel substitutions (T285A, S457P) with fluconazole resistance needs to be further verified by site-directed mutagenesis.

  10. ERG11 mutations associated with azole resistance in Candida albicans isolates from vulvovaginal candidosis patients

    Institute of Scientific and Technical Information of China (English)

    Bin; Wang; Li-Hua; Huang; Ji-Xue; Zhao; Man; Wei; Hua; Fang; Dan-Yang; Wang; Hong-Fa; Wang; Ji-Gang; Yin; Mei; Xiang

    2015-01-01

    Objective: To investigate the azole susceptibility of Candida albicans(C.albicans)from vulvovaginal candidosis patients and to analyze the relationship between ERG11 gene mutations in these isolates and azole resistance.Methods: Three hundred and two clinical isolates of Candida species were collected.Azole susceptibility was tested in vitro in microdilution studies. The ERG11 genes of 17 isolates of C. albicans(2 susceptibles, 5 dose-dependent resistants and 10 resistants) were amplified and sequenced.Results: Of the 302 isolates collected, 70.2% were C. albicans, of which 8.5%, 3.8% and4.2% were resistant to fluconazole, itraconazole and voriconazole, respectively. In total,27 missense mutations were detected in ERG11 genes from resistant/susceptible dosedependent isolates. Among them, Y132 H, A114 S, and Y257 H substitutions were most prevalent and were known to cause fluconazole resistance. G464 S and F72 S also have been proved to cause fluconazole resistance. Two novel substitutions(T285A, S457P) in hotspot regions were identified.Conclusions: Twenty seven mutations in the ERG11 gene were identified in azoleresistant C. albicans isolates, which indicated a possible relation with the increase in resistance to azole drugs and the recurrence of vulvovaginal candidosis. The relationship of two novel substitutions(T285A, S457P) with fluconazole resistance needs to be further verified by site-directed mutagenesis.

  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. 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...

  13. Candida albicans and Candida stellatoidea, in contrast to other Candida species, bind iC3b and C3d but not C3b.

    OpenAIRE

    Heidenreich, F; Dierich, M.P.

    1985-01-01

    It was demonstrated that complement-coated sheep erythrocytes bind to Candida albicans cells grown in serum-free RPMI 1640 medium. Testing of purified complement components proved that iC3b and C3d were responsible for the reaction, whereas C3b and C3b-H reacted only slightly if at all. Binding occurred only to C. albicans and C. stellatoidea, not to other species pathogenic to humans. There was evidence of a lectinlike nature of the effect.

  14. 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

  15. Ocorrência de Candida albicans em intestinos de bovinos

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    Souza W.A.

    2003-01-01

    Full Text Available Foram realizadas a identificação e a sorotipagem de C. albicans isoladas de fezes de bovinos em amamentação natural. Para o isolamento, utilizou-se o meio seletivo e diferencial de Pagano Levin, adicionado de bifenilo na concentração final de 0,1%. De 210 bovinos inicialmente considerados, 70 adultos, 68 bezerros após o desmame e 72 bezerros em fase de amamentação natural, observou-se positividade para C. albicans somente em nove amostras de fezes de bezerros em fase de amamentação (12,5%. A determinação do sorotipo por meio de provas de aglutinação direta em lâmina, com soros monoespecíficos, revelou que a totalidade das amostras isoladas pertencia ao sorotipo A. O bifenilo na concentração de 0,1% mostrou-se inibitório para a maioria dos bolores sem, aparentemente, afetar a viabilidade de C. albicans. O isolamento de C. albicans somente a partir de fezes de bezerros em amamentação, provavelmente, está relacionado à dieta láctea.

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

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    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

  17. Potent Activities of Roemerine against Candida albicans and the Underlying Mechanisms.

    Science.gov (United States)

    Ma, Chaoyu; Du, Faya; Yan, Lan; He, Gonghao; He, Jianchang; Wang, Chengying; Rao, Gaoxiong; Jiang, Yuanying; Xu, Guili

    2015-01-01

    Roemerine (RM) is an aporphine alkaloid isolated from the fresh rattan stem of Fibraurea recisa, and it has been demonstrated to have certain antifungal activity. This study aimed to investigate the antifungal activity of RM and the underlying mechanisms in Candida albicans (C. albicans). The in vitro antifungal activity of RM was evaluated by a series of experiments, including the XTT reduction assay, confocal laser scanning microscopy assay, scanning electron microscope assay. Results showed that 1 μg/mL RM inhibited biofilm formation significantly (p anti-biofilm mechanism may be related to the cAMP pathway. PMID:26426004

  18. 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 ...

  19. Activity of antimicrobial peptide mimetics in the oral cavity: I. Activity against biofilms of Candida albicans.

    Science.gov (United States)

    Hua, J; Yamarthy, R; Felsenstein, S; Scott, R W; Markowitz, K; Diamond, G

    2010-12-01

    Naturally occurring antimicrobial peptides hold promise as therapeutic agents against oral pathogens such as Candida albicans but numerous difficulties have slowed their development. Synthetic, non-peptidic analogs that mimic the properties of these peptides have many advantages and exhibit potent, selective antimicrobial activity. Several series of mimetics (with molecular weight oral Candida strains as a proof-of-principle for their antifungal properties. One phenylalkyne and several arylamide compounds with reduced mammalian cytotoxicities were found to be active against C. albicans. These compounds demonstrated rapid fungicidal activity in liquid culture even in the presence of saliva, and demonstrated synergy with standard antifungal agents. When assayed against biofilms grown on denture acrylic, the compounds exhibited potent fungicidal activity as measured by metabolic and fluorescent viability assays. Repeated passages in sub-minimum inhibitory concentration levels did not lead to resistant Candida, in contrast to fluconazole. Our results demonstrate the proof-of principle for the use of these compounds as anti-Candida agents, and their further testing is warranted as novel anti-Candida therapies.

  20. 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.

  1. [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

  2. 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

  3. Influence of aeration of Candida albicans during culturing on their surface aggregation in the presence of adhering Streptococcus gordonii

    NARCIS (Netherlands)

    Millsap, KW; van der Mei, HC; Busscher, HJ; Bos, R.R.M.

    1999-01-01

    Candida albicans surfaces are extremely sensitive to changes in growth conditions. In this study, adhesion to glass of aerated and non-aerated C. albicans ATCC 10261 in the presence and absence of adhering Streptococcus gordonii NCTC 7869 was determined in a parallel plate flow chamber. In addition,

  4. Effects of Low-Level Laser Irradiation on the Pathogenicity of Candida albicans: In Vitro and in Vivo Study

    NARCIS (Netherlands)

    Seyedmousavi Tasieh, S.; Hashemi, S.J.; Rezaie, S.; Fateh, M.; Djavid, G.E.; Zibafar, E.; Morsali, F.; Zand, N.; Alinaghizadeh, M.; Ataie-Fashtami, L.

    2014-01-01

    Abstract Objective: The purpose of this study was to evaluate the effects of low-level laser irradiation (LLLI) on the in vitro growth characteristics and in vivo pathogenicity of Candida albicans in a murine model in the absence of a photosensitizer. Background data: C. albicans is an opportunistic

  5. Effect of Shark Liver Oil on Peritoneal Murine Macrophages in Responses to Killed-Candida albicans

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    Monire Hajimoradi

    2009-09-01

    Full Text Available Objective(sShark Liver Oil (SLO is an immunomodulator. Macrophages play a key role in host defense against pathogens like fungi. Candida albicans have mechanisms to escape immune system. We determined the effect of killed-Candida on the in vitro viability of macrophages and the effect of SLO on augmentation of this potency.Materials and MethodsPeritoneal macrophages were separated and cultured (3×105/well. At first, the effect of killed-Candida (200 cells/well on macrophage viability was evaluated, using MTT test. Then, MTT was performed on macrophages stimulated with killed-Candida in the presence of SLO. ResultsKilled-Candida suppressed the ability of MTT reduction and hence macrophages viability (P=0.026, but addition of SLO (100 mg/ml significantly enhanced cell viability (P=0.00. So, SLO could neutralize the inhibitory effect of Candida.ConclusionSimultaneous with cytotoxic effect of killed-Candida cells on macrophages viability, SLO augment macrophages viability. So, it can be applied in candidiasis as a complement.

  6. Candida albicans--adriamycin interactions: ultrastructural and spectrofluorometric study of whole yeasts and spheroplasts.

    Science.gov (United States)

    Bobichon, H; Bussy, V; Angiboust, J F; Manfait, M; Bouchet, P; Jardillier, J C

    1990-01-01

    The occurrence of candidiasis in cancer patients who undergo chemotherapy requires the interrelation of Candida albicans and the antimitotic drug Adriamycin (ADM) which is well known as an intercalating agent. The whole yeasts were not affected by 2 h of contact with the drug at 10(-4) M neither for their growth curve nor for their ultrastructure, despite the presence of free ADM on their surface. Spheroplasts displayed a delay in their growth and exhibited altered nucleoli with segregation of their granular and fibrillar components. The modified emission spectrum of ADM, determined by spectrofluorometry, corresponded neither to the free ADM nor to the DNA-bound drug, but it could be related to a metabolite of the drug. The cell wall appeared to be one of the main sites for ADM resistance of Candida albicans in vitro. PMID:2085691

  7. Nocvel potential targets and related genes of transcription factor Caplp in Candida albicans 1

    Institute of Scientific and Technical Information of China (English)

    YahWANG; Yong-bingCAO; Xin-mingJIA; De-junWANG; ZhengXU; HuiSHEN; KangYING; Wan-shengCHEN; Yuan-yingJIANG

    2005-01-01

    AIM Capl p, encoded by CAP1 in Candida albicans, is highly homologous to Saccharomyces cerevisiae transcription factor Yapl p. It has been associated with tolerance to oxidative stress and resistance to a variety of toxicants previously. We used homemade microarray to reveal Capl p related genes in a broad spectrum as well as to lucubrate the functions of Capl p. METHODS Microarray analysis was used to identify differentially expressed genes between CAP1 deletion strain CJD21 and its parental strain CAI4. CAP1 over-expression strain was constructed to confirm the relationship between CAP1 and some differentially expressedgenes. Bioinformatics was applied to reveal promoters with Capl p binding site as well as the clusters of differentially expressed genes. RT-PCR and drug efflux analysis were used to lucubrate the functions of Caplp in Candida albicans.

  8. Genotypes of Candida albicans isolated from healthy individuals and their distribution in patients with oral candidiasis.

    Science.gov (United States)

    Takagi, Yuki; Fukano, Hideo; Shimozato, Kazuo; Tanaka, Reiko; Horii, Toshinobu; Kawamoto, Fumihiko; Kanbe, Toshio

    2013-12-01

    For the study of Candida albicans genotypes involved in development of candidiasis, Candida albicans isolates were collected from healthy volunteers and patients with oral candidiasis and genotyped on the basis of 25S rDNA and microsatellite polymorphisms. In the microsatellite analysis using two microsatellite markers (CDC3 and CAI), 63 healthy volunteer isolates were classified into 35 genotypes (allelic relations to CDC3 alleles 1:2/CAI alleles 1:2), among which genotypes II (115:119/23:23), III (115:123/18:27), and V (123:127/32:41) were found at frequencies of 12.7%, 7.9%, and 7.9%, respectively. In 68 oral candidiasis isolates classified into 39 genotypes, genotypes II and III were identified in 4.4% and 20.6% of the isolates, respectively. The frequency of genotype III was higher in the candidiasis isolates than in the healthy isolates (p oral candidiasis.

  9. A chemometric approach for prediction of antifungal activity of some benzoxazole derivatives against Candida albicans

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    Podunavac-Kuzmanović Sanja O.

    2012-01-01

    Full Text Available The purpose of the article is to promote and facilitate prediction of antifungal activity of the investigated series of benzoxazoles against Candida albicans. The clinical importance of this investigation is to simplify design of new antifungal agents against the fungi which can cause serious illnesses in humans. Quantitative structure activity relationship analysis was applied on nineteen benzoxazole derivatives. A multiple linear regression (MLR procedure was used to model the relationships between the molecular descriptors and the antifungal activity of benzoxazole derivatives. Two mathematical models have been developed as a calibration models for predicting the inhibitory activity of this class of compounds against Candida albicans. The quality of the models was validated by the leave-one-out technique, as well as by the calculation of statistical parameters for the established model. [Projekat Ministarstva nauke Republike Srbije, br. 172012 i br. 172014

  10. 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.

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

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    Seung-Bae Lee

    2016-03-01

    Full Text Available 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 using a broth microdilution method. Also, a killing curve assay was conducted to investigate the kinetics of the anti- fungal action. Results: BV and SBV showed antifungal activity against 10 clinical isolates of C. albicans that were cultured from blood and the vagina by using disk diffusion method. The MIC values obtained for clinical isolates by using the broth microdilution method varied from 62.5 μg/ mL to 125 μg/mL for BV and from 15.63 μg/mL to 62.5 μg/mL for SBV. In the killing-curve assay, SBV behaved as amphotericin B, which was used as positive control, did. The antifungal efficacy of SBV was much higher than that of BV. Conclusion: BV and SBV showed antifungal activity against C. albicans clinical strains that were isolated from blood and the vagina. Especially, SBV might be a candidate for a new antifungal agent against C. albicans clinical isolates.

  12. Rac1 dynamics in the human opportunistic fungal pathogen Candida albicans.

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    Romain Vauchelles

    Full Text Available The small Rho G-protein Rac1 is highly conserved from fungi to humans, with approximately 65% overall sequence identity in Candida albicans. As observed with human Rac1, we show that C. albicans Rac1 can accumulate in the nucleus, and fluorescence recovery after photobleaching (FRAP together with fluorescence loss in photobleaching (FLIP studies indicate that this Rho G-protein undergoes nucleo-cytoplasmic shuttling. Analyses of different chimeras revealed that nuclear accumulation of C. albicans Rac1 requires the NLS-motifs at its carboxyl-terminus, which are blocked by prenylation of the adjacent cysteine residue. Furthermore, we show that C. albicans Rac1 dynamics, both at the plasma membrane and in the nucleus, are dependent on its activation state and in particular that the inactive form accumulates faster in the nucleus. Heterologous expression of human Rac1 in C. albicans also results in nuclear accumulation, yet accumulation is more rapid than that of C. albicans Rac1. Taken together our results indicate that Rac1 nuclear accumulation is an inherent property of this G-protein and suggest that the requirements for its nucleo-cytoplasmic shuttling are conserved from fungi to humans.

  13. 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

  14. Anaerobic bacteria grow within Candida albicans biofilms and induce biofilm formation in suspension cultures.

    Science.gov (United States)

    Fox, Emily P; Cowley, Elise S; Nobile, Clarissa J; Hartooni, Nairi; Newman, Dianne K; Johnson, Alexander D

    2014-10-20

    The human microbiome contains diverse microorganisms, which share and compete for the same environmental niches. A major microbial growth form in the human body is the biofilm state, where tightly packed bacterial, archaeal, and fungal cells must cooperate and/or compete for resources in order to survive. We examined mixed biofilms composed of the major fungal species of the gut microbiome, Candida albicans, and each of five prevalent bacterial gastrointestinal inhabitants: Bacteroides fragilis, Clostridium perfringens, Escherichia coli, Klebsiella pneumoniae, and Enterococcus faecalis. We observed that biofilms formed by C. albicans provide a hypoxic microenvironment that supports the growth of two anaerobic bacteria, even when cultured in ambient oxic conditions that are normally toxic to the bacteria. We also found that coculture with bacteria in biofilms induces massive gene expression changes in C. albicans, including upregulation of WOR1, which encodes a transcription regulator that controls a phenotypic switch in C. albicans, from the "white" cell type to the "opaque" cell type. Finally, we observed that in suspension cultures, C. perfringens induces aggregation of C. albicans into "mini-biofilms," which allow C. perfringens cells to survive in a normally toxic environment. This work indicates that bacteria and C. albicans interactions modulate the local chemistry of their environment in multiple ways to create niches favorable to their growth and survival.

  15. Identification of Drosophila gene products required for phagocytosis of Candida albicans.

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    Shannon L Stroschein-Stevenson

    2006-01-01

    Full Text Available Phagocytosis is a highly conserved aspect of innate immunity. We used Drosophila melanogaster S2 cells as a model system to study the phagocytosis of Candida albicans, the major fungal pathogen of humans, by screening an RNAi library representing 7,216 fly genes conserved among metazoans. After rescreening the initial genes identified and eliminating certain classes of housekeeping genes, we identified 184 genes required for efficient phagocytosis of C. albicans. Diverse biological processes are represented, with actin cytoskeleton regulation, vesicle transport, signaling, and transcriptional regulation being prominent. Secondary screens using Escherichia coli and latex beads revealed several genes specific for C. albicans phagocytosis. Characterization of one of those gene products, Macroglobulin complement related (Mcr, shows that it is secreted, that it binds specifically to the surface of C. albicans, and that it promotes its subsequent phagocytosis. Mcr is closely related to the four Drosophila thioester proteins (Teps, and we show that TepII is required for efficient phagocytosis of E. coli (but not C. albicans or Staphylococcus aureus and that TepIII is required for the efficient phagocytosis of S. aureus (but not C. albicans or E. coli. Thus, this family of fly proteins distinguishes different pathogens for subsequent phagocytosis.

  16. 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.

  17. 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

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. Variability in expression of cell surface antigens of Candida albicans during morphogenesis.

    OpenAIRE

    Brawner, D L; Cutler, J. E.

    1986-01-01

    The location and expression of two different cell surface antigens on germinating and nongerminating Candida albicans cells was examined by using transmission electron microscopy after labeling with monoclonal antibodies (H9 or C6) and immunocolloidal gold. Immunodeterminant expression of the two carbohydrate antigens was followed from early germination events through 20 h of development. The determinant detected by H9 antibody, which was initially lost from the mother cell surface and prefer...

  3. Antifungal activities of Terminalia ivorensis A. Chev. bark extracts against Candida albicans and Aspergillus fumigatus.

    OpenAIRE

    Ouattara Sitapha; KPOROU KOUASSI ELISEE; Djaman Allico Joseph

    2013-01-01

    Abstract The present study was undertaken to evaluate in vitro antifungal activity of aqueous and hydroacoholic extracts from bark of Terminalia ivorensis A. Chev. (Combretaceae). In vitro antifungal activity of all the extracts was done by agar slant double dilution method. Candida albicans and Aspergillus fumigatus clinically important strains were used for the study. ketoconazole was used as standards for antifungal assay. Antifungal activity was determinated by evaluating of antifung...

  4. 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...

  5. 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...

  6. Hydrophobic surface protein masking by the opportunistic fungal pathogen Candida albicans.

    OpenAIRE

    Hazen, K C; Hazen, B W

    1992-01-01

    Ultrastructural and biochemical analyses of hydrophobic and hydrophilic yeast cell surface proteins of Candida albicans were performed. Hydrophobic and hydrophilic yeast cells were obtained by growth at 23 and 37 degrees C, respectively. In addition, hydrophilic yeast cells were converted to surface hydrophobicity by treatment with tunicamycin and dithiothreitol. When freeze-etched cells were examined, the temperature-induced hydrophilic cells had long (0.198 micron), compact, evenly distribu...

  7. Differential adherence of hydrophobic and hydrophilic Candida albicans yeast cells to mouse tissues.

    OpenAIRE

    Hazen, K C; Brawner, D L; Riesselman, M H; Jutila, M A; Cutler, J E

    1991-01-01

    Using an ex vivo binding assay, we previously demonstrated that yeast cells grown at 37 degrees C display binding specificity in mouse spleen, lymph node, and kidney tissues. In spleen and lymph node tissues, binding was predominantly in regions rich in macrophages. Here, we tested the possibility that hydrophobic and hydrophilic cells bind differentially to host tissues. Hydrophobic and hydrophilic yeast cells of four Candida albicans strains were incubated for 15 min at 4 degrees C with cry...

  8. Relationship between germination of Candida albicans and increased adherence to human buccal epithelial cells.

    OpenAIRE

    Kimura, L H; Pearsall, N N

    1980-01-01

    A strong correlation was shown between germination and increased adherence of Candida albicans to human buccal epithelial cells, indicating that germination or other changes in the fungi accompanying germination were responsible for enhanced adherence. Partial inhibition of germination by cysteine resulted in a comparably lower adherence. Preferential adherence of germinated fungi occurred in competition assays with nongerminated and germinated fungi. The enhanced adherence to human mucosal c...

  9. Identification of two germ-tube-specific cell wall antigens of Candida albicans.

    OpenAIRE

    Ponton, J; J. M. Jones

    1986-01-01

    Outer cell wall layers of intact yeast- and mycelial-phase Candida albicans B311 were extracted with dithiothreitol. Antisera against mycelial-phase organisms were absorbed with yeast-phase organisms or yeast-phase extract and used to stain Western blots of sodium dodecyl sulfate-polyacrylamide gels loaded with yeast- and mycelial-phase extracts. Autoradiography of gels loaded with extracts from organisms surface labeled with 125I was used to detect surface antigens containing proteins. Antig...

  10. PRODUCTION OF A HUMAN RECOMBINANT ANTIBODY AGAINST SEROTYPE A CANDIDA ALBICANS

    OpenAIRE

    Jafari, A. A.

    2005-01-01

    After using 3 different generations of antibodies including human and non-human hyperimmune sera, monoclonal antibodies and chimeric antibodies, more recently a newer approach has been developed in which the antibody genes are cloned directly from a patient peripheral B-lymphocytes and expressed in a host like E. coli. In this study the Candida albicans serotype A (NCTC 3153) mannan was purified using a modified Fehling method and used for selection of human recombinant antibody from a C. alb...

  11. Protection against murine disseminated candidiasis mediated by a Candida albicans-specific T-cell line.

    OpenAIRE

    Sieck, T G; Moors, M A; Buckley, H R; Blank, K J

    1993-01-01

    The role of T lymphocytes in disseminated candidiasis in a mouse model of irradiation-induced immunosuppression was investigated. A continuously cultured Candida albicans-specific T-cell line mediated protection of sublethally irradiated mice from disseminated candidiasis as measured by both the fungal load in the kidneys and mortality. These results are the first to demonstrate directly a role for antigen-specific T cells in the protective immune response against murine disseminated candidia...

  12. 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...

  13. Influence of artificial saliva in biofilm formation of Candida albicans in vitro

    Directory of Open Access Journals (Sweden)

    Michelle Peneluppi Silva

    2012-02-01

    Full Text Available Due to the increase in life expectancy, new treatments have emerged which, although palliative, provide individuals with a better quality of life. Artificial saliva is a solution that contains substances that moisten a dry mouth, thus mimicking the role of saliva in lubricating the oral cavity and controlling the existing normal oral microbiota. This study aimed to assess the influence of commercially available artificial saliva on biofilm formation by Candida albicans. Artificial saliva I consists of carboxymethylcellulose, while artificial saliva II is composed of glucose oxidase, lactoferrin, lysozyme and lactoperoxidase. A control group used sterile distilled water. Microorganisms from the oral cavity were transferred to Sabouraud Dextrose Agar and incubated at 37°C for 24 hours. Colonies of Candida albicans were suspended in a sterile solution of NaCl 0.9%, and standardisation of the suspension to 106 cells/mL was achieved. The acrylic discs, immersed in artificial saliva and sterile distilled water, were placed in a 24-well plate containing 2 mL of Sabouraud Dextrose Broth plus 5% sucrose and 0.1 mL aliquot of the Candida albicans suspension. The plates were incubated at 37°C for 5 days, the discs were washed in 2 mL of 0.9% NaCl and placed into a tube containing 10 mL of 0.9% NaCl. After decimal dilutions, aliquots of 0.1 mL were seeded on Sabouraud Dextrose Agar and incubated at 37°C for 48 hours. Counts were reported as CFU/mL (Log10. A statistically significant reduction of 29.89% (1.45 CFU/mL of Candida albicans was observed in saliva I when compared to saliva II (p = 0.002, considering p≤0.05.

  14. 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...

  15. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

  17. 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

  18. 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

  19. In vitro effects of glycyrrhetinic acid on the growth of clinical isolates of Candida albicans.

    Science.gov (United States)

    Pellati, Donatella; Fiore, Cristina; Armanini, Decio; Rassu, Mario; Bertoloni, Giulio

    2009-04-01

    Compounds derived from Glycyrrhiza glabra L. root have been used widely for centuries for their numerous therapeutic properties. The present study aimed to test the in vitro activity against Candida albicans strains of the compound 18-beta glycyrrhetinic acid (18-beta GA), derived from the root of Glycyrrhiza species. This antimicrobial activity was assessed using the National Committee for Clinical Laboratory Standards (NCCLS) method on C. albicans strains that were isolated from patients with recurrent vulvovaginal candidiasis (RVVC). The in vitro growth of the C. albicans strains was markedly reduced, in a pH-dependent manner, by relatively low doses (6.2 microg/mL) of 18-beta GA. The results demonstrate that 18-beta GA is a promising biological alternative for the topical treatment of recurrent vulvovaginal candidiasis (RVVC). PMID:19067381

  20. Protocol for Determination of the Persister Subpopulation in Candida Albicans Biofilms.

    Science.gov (United States)

    De Brucker, Katrijn; De Cremer, Kaat; Cammue, Bruno P A; Thevissen, Karin

    2016-01-01

    In contrast to planktonic cultures of the human fungal pathogen Candida albicans, C. albicans biofilms can contain a persister subpopulation that is tolerant to high concentrations of currently used antifungals. In this chapter, the method to determine the persister fraction in a C. albicans biofilm treated with an antifungal compound is described. To this end, a mature biofilm is developed and subsequently treated with a concentration series of the antifungal compound of interest. Upon incubation, the fraction of surviving biofilm cells is determined by plating and plotted versus the used concentrations of the antifungal compound. If a persister subpopulation in the biofilm is present, the dose-dependent killing of the biofilm cells results in a biphasic killing pattern.

  1. In vitro effects of Salvia officinalis L. essential oil on Candida albicans

    Institute of Scientific and Technical Information of China (English)

    Tularat Sookto; Theerathavaj Srithavaj; Sroisiri Thaweboon; Boonyanit Thaweboon; Binit Shrestha

    2013-01-01

    Objective: To determine the anticandidal activities of Salvia officinalis L. (S. officinalis) essential oil against Candida albicans (C. albicans) and the inhibitory effects on the adhesion of C. albicans to polymethyl methacrylate (PMMA) resin surface. Methods: Disc diffusion method was first used to test the anticandidal activities of the S. officinalis L. essential oil against the reference strain (ATCC 90028) and 2 clinical strains of C. albicans. Then the minimal inhibitory concentration (MIC) and minimal lethal concentration (MLC) were determined by modified membrane method. The adhesion of C. albicans to PMMA resin surface was assessed after immersion with S. officinalis L. essential oil at various concentrations of 1×MIC, 0.5×MIC and 0.25×MIC at room temperature for 30 min. One-way ANOVA was used to compare the Candida cell adhesion with the pretreatment agents and Tukey’s test was used for multiple comparisons. Results: S. officinalis L. essential oil exhibited anticandidal activity against all strains of C. albicans with inhibition zone ranging from 40.5 mm to 19.5 mm. The MIC and MLC of the oil were determined as 2.780 g/L against all test strains. According to the effects on C. albicans adhesion to PMMA resin surface, it was found that immersion in the essential oil at concentrations of 1×MIC (2.780 g/L), 0.5×MIC (1.390 g/L) and 0.25×MIC (0.695 g/L) for 30 min significantly reduced the adhesion of all 3 test strains to PMMA resin surface in a dose dependent manner (P<0.05). 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.

  2. 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.

  3. Inhibitory Effect of Curcumin on Candida-albicans compared with Nystatin: an in-vitro Study

    Directory of Open Access Journals (Sweden)

    Neda Babaii

    2016-10-01

    Full Text Available Introduction: Curcumin is the active ingredient in the traditional herbal remedy and dietary spice turmeric (Curcuma longa. Curcumin has a surprisingly wide range of beneficial properties, including anti-inflammatory, antioxidant, chemopreventive and chemotherapeutic activity. on basis of recent studies; it has antifungal and antibacterial effects. The aim of this study was in-vitro evaluation of antifungal effect of curcumin on candida albicans and comparing it with nystatin. Methods: after preparing curcumin powder, 3 laboratory methods were used to evaluate antifungal effect. The first method was cell count technique, used to evaluate the amount of candida albicans after time, in different concentrations of curcumin in Dimethyl sulfoxide (DMSO. The second was cup bioassay, in which inhibitory a zone of curcumin in DMSO was evaluated in sabouraud culture plates; and in third method, inhibitory zones of dried disks; which contained curcumin in DMSO were evaluated. Results: the result of all three methods showed that curcumin has antifungal effect and this effect increases in more concentrations. Conclusion: curcumin has apparent and dose dependent antifungal effect on candida albicans.

  4. 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.

  5. Top-down characterization data on the speciation of the Candida albicans immunome in candidemia.

    Science.gov (United States)

    Pitarch, Aida; Nombela, César; Gil, Concha

    2016-03-01

    The characterization of pathogen-specific antigenic proteins at the protein species level is crucial in the development and molecular optimization of novel immunodiagnostics, vaccines or immunotherapeutics for infectious diseases. The major requirements to achieve this molecular level are to obtain 100% sequence coverage and identify all post-translational modifications of each antigenic protein species. In this article, we show nearly complete sequence information for five discrete antigenic species of Candida albicans Tdh3 (glyceraldehyde-3-phosphate dehydrogenase), which have been reported to be differentially recognized both among candidemia patients and between candidemia and control patients. A comprehensive description of the top-down immunoproteomic strategy used for seroprofiling at the C. albicans protein species level in candidemia as well as for the chemical characterization of this immunogenic protein (based on high-resolution 2-DE, Western blotting, peptide mass fingerprinting, tandem mass spectrometry and de novo peptide sequencing) is also provided. The top-down characterization data on the speciation of the C. albicans immunome in candidemia presented here are related to our research article entitled "Seroprofiling at the Candida albicans protein species level unveils an accurate molecular discriminator for candidemia" (Pitarch et al., J. Proteomics, 2015, http://dx.doi.org/10.1016/j.jprot.2015.10.022). PMID:26862568

  6. Top-down characterization data on the speciation of the Candida albicans immunome in candidemia

    Directory of Open Access Journals (Sweden)

    Aida Pitarch

    2016-03-01

    Full Text Available The characterization of pathogen-specific antigenic proteins at the protein species level is crucial in the development and molecular optimization of novel immunodiagnostics, vaccines or immunotherapeutics for infectious diseases. The major requirements to achieve this molecular level are to obtain 100% sequence coverage and identify all post-translational modifications of each antigenic protein species. In this article, we show nearly complete sequence information for five discrete antigenic species of Candida albicans Tdh3 (glyceraldehyde-3-phosphate dehydrogenase, which have been reported to be differentially recognized both among candidemia patients and between candidemia and control patients. A comprehensive description of the top-down immunoproteomic strategy used for seroprofiling at the C. albicans protein species level in candidemia as well as for the chemical characterization of this immunogenic protein (based on high-resolution 2-DE, Western blotting, peptide mass fingerprinting, tandem mass spectrometry and de novo peptide sequencing is also provided. The top-down characterization data on the speciation of the C. albicans immunome in candidemia presented here are related to our research article entitled “Seroprofiling at the Candida albicans protein species level unveils an accurate molecular discriminator for candidemia” (Pitarch et al., J. Proteomics, 2015, http://dx.doi.org/10.1016/j.jprot.2015.10.022.

  7. 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.

  8. The Clinical Candidate VT-1161 Is a Highly Potent Inhibitor of Candida albicans CYP51 but Fails To Bind the Human Enzyme

    OpenAIRE

    Warrilow, A. G. S.; Hull, C. M.; Parker, J. E.; Garvey, E P; Hoekstra, W. J.; Moore, W. R.; Schotzinger, R. J.; Kelly, D. E.; Kelly, S. L.

    2014-01-01

    The binding and cytochrome P45051 (CYP51) inhibition properties of a novel antifungal compound, VT-1161, against purified recombinant Candida albicans CYP51 (ERG11) and Homo sapiens CYP51 were compared with those of clotrimazole, fluconazole, itraconazole, and voriconazole. VT-1161 produced a type II binding spectrum with Candida albicans CYP51, characteristic of heme iron coordination. The binding affinity of VT-1161 for Candida albicans CYP51 was high (dissociation constant [Kd], ≤39 nM) an...

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Mechanisms of the antifungal action of marine metagenome-derived peptide, MMGP1, against Candida albicans.

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    Muthuirulan Pushpanathan

    Full Text Available BACKGROUND: Development of resistant variants to existing antifungal drugs continues to be the serious problem in Candida albicans-induced fungal pathogenesis, which has a considerable impact on animal and human health. Identification and characterization of newer drugs against C. albicans is, therefore, essential. MMGP1 is a direct cell-penetrating peptide recently identified from marine metagenome, which was found to possess potent antifungal activity against C. albicans. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we investigated the mechanism of antifungal action of MMGP1 against C. albicans. Agarose gel shift assay found the peptide to be having a remarkable DNA-binding ability. The modification of the absorption spectra and fluorescence quenching of the tryptophyl residue correspond to the stacking between indole ring and nucleotide bases. The formation of peptide-DNA complexes was confirmed by fluorescence quenching of SYTO 9 probe. The interaction of peptide with plasmid DNA afforded protection of DNA from enzymatic degradation by DNase I. In vitro transcription of mouse β-actin gene in the presence of peptide led to a decrease in the level of mRNA synthesis. The C. albicans treated with MMGP1 showed strong inhibition of biosynthetic incorporation of uridine analog 5-ethynyluridine (EU into nascent RNA, suggesting the peptide's role in the inhibition of macromolecular synthesis. Furthermore, the peptide also induces endogenous accumulation of reactive oxygen species (ROS in C. albicans. MMGP1 supplemented with glutathione showed an increased viability of C. albicans cells. The hyper-produced ROS by MMGP1 leads to increased levels of protein carbonyls and thiobarbituric acid reactive substances and it also causes dissipation of mitochondrial membrane potential and DNA fragmentation in C. albicans cells. CONCLUSION: And Significance: Therefore, the antifungal activity of MMGP1 could be attributed to its binding with DNA, causing

  11. Adding Biotin to Parenteral Nutrition Solutions Without Lipid Accelerates the Growth of Candida albicans

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    Kuwahara, Takashi; Kaneda, Shinya; Shimono, Kazuyuki

    2016-01-01

    Background: We have previously demonstrated that Candida albicans requires multivitamins (MVs) or lipid to increase rapidly in parenteral nutrition (PN) solutions. In this study, in detail, the effects of vitamins on the growth of C. albicans in PN solutions without lipid were investigated. Methods: In the 1st experiment, a commercial PN solution without lipid was supplemented with water-soluble vitamins (SVs: vitamins B1, B2, B6, B12 and C, folic acid, nicotinamide, biotin and panthenol), water-insoluble vitamins (IVs: vitamins A, D, E and K) or both (MVs). In the 2nd experiment, the test solutions were prepared by supplementing the PN solution with one of each or all of the SVs. In the 3rd experiment, another commercial peripheral PN (PPN) solution without lipid was supplemented with SVs, nicotinic acid, biotin or both nicotinic acid and biotin. In each of the experiments, a specified number of C. albicans organisms was added to each test solution, and all of the test solutions were allowed to stand at room temperature (23-26ºC). The number of C. albicans was counted at 0, 24, 48 and 72 hours after the addition of the organism. Results: In the 1st experiment, the C. albicans increased rapidly in the PN solution supplemented with the SVs, but increased slowly without the SVs, regardless of the addition of the IVs. In the 2nd experiment, the C. albicans increased rapidly in the PN solution supplemented with the SVs or biotin, but increased slowly with each of the other water-soluble vitamins. In the 3rd experiment, the C. albicans increased rapidly in the PPN solution supplemented with the SVs or biotin, but increased slowly with the addition of nicotinic acid. Conclusions: These results suggested that adding MVs or SVs to PN solutions without lipid promotes the growth of C. albicans, and that this effect is mostly attributable to biotin. PMID:27648003

  12. 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

  13. Candida albicans menengitis in a newborn with classical galactosemia

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    Altunhan, Hüseyin; Annagür, Ali; Ertuğrul, Sabahattin; Konak, Murat; Yüksekkaya, Hasan Ali; Örs, Rahmi

    2012-01-01

    Classical galactosemia is a rarely seen carbohydrate metabolism disorder. The frequency of sepsis significantly increases in patients with galactosemia. The most common agent causing sepsis is E. coli. Sepsis due to fungus in patients with galactosemia is rarely reported. Candida is an important cause of sepsis in newborn intensive care units especially in newborns with underlying risk factors such as prematurity and low birth weight. Although the most common etiologic agent of sepsis is E. c...

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

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    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...

  15. An in vitro study on effect of Delmopinol application on Candida albicans adherence on heat cured denture base acrylic resin: A thorough study

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    Deshraj Jain

    2013-01-01

    Conclusion: Heat-cured acrylic resin shows greater reduction in adherence of Candida albicans by contamination after Delmopinol application as compared with contamination before Delmopinol application.

  16. Antifungal activity of four honeys of different types from Algeria against pathogenic yeast:Candida albicans and Rhodotorula sp.

    Institute of Scientific and Technical Information of China (English)

    Ahmed Moussa; Djebli Noureddine; Aissat Saad; Meslem Abdelmelek; Benhalima Abdelkader

    2012-01-01

    Objective: To evaluate the antifungal activity of four honeys of different types from Algeria against pathogenic yeast i.e. Candida albicans (C. albicans) and Rhodotorula sp. Methods:Four Algeria honeys of different botanical origin were analyzed to test antifungal effect against C. albicans, and Rhodotorula sp. Different concentrations (undiluted, 10%, 30%, 50%and 70%w/v) of honey were studied in vitro for their antifugal activity using C. albicans and Rhodotorula sp. as fungal strains. Results:The range of the diameter of zone of inhibition of various concentrations of tested honeys was (7-23 mm) for Rhodotorula sp., while C. albicans showed clearly resistance towards all concentrations used. The MICs of tested honey concentrations against C. albicans and Rhodotorula sp. were (70.09-93.48)%and (4.90-99.70)%v/v, respectively. Conclusions:This study demonstrates that, in vitro, these natural products have clearly an antifungal activity against Rhodotorula sp. and C. albicans.

  17. A GATA transcription factor recruits Hda1 in response to reduced Tor1 signaling to establish a hyphal chromatin state in Candida albicans.

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    Yang Lu

    Full Text Available Candida albicans is an important opportunistic fungal pathogen of immunocompromised individuals. One critical virulence attribute is its morphogenetic plasticity. Hyphal development requires two temporally linked changes in promoter chromatin, which is sequentially regulated by temporarily clearing the transcription inhibitor Nrg1 upon activation of the cAMP/PKA pathway and promoter recruitment of the histone deacetylase Hda1 under reduced Tor1 signaling. Molecular mechanisms for the temporal connection and the link to Tor1 signaling are not clear. Here, through a forward genetic screen, we report the identification of the GATA family transcription factor Brg1 as the factor that recruits Hda1 to promoters of hypha-specific genes during hyphal elongation. BRG1 expression requires both the removal of Nrg1 and a sub-growth inhibitory level of rapamycin; therefore, it is a sensitive readout of Tor1 signaling. Interestingly, promoters of hypha-specific genes are not accessible to Brg1 in yeast cells. Furthermore, ectopic expression of Brg1 cannot induce hyphae, but can sustain hyphal development. Nucleosome mapping of a hypha-specific promoter shows that Nrg1 binding sites are in nucleosome free regions in yeast cells, whereas Brg1 binding sites are occupied by nucleosomes. Nucleosome disassembly during hyphal initiation exposes the binding sites for both regulators. During hyphal elongation, Brg1-mediated Hda1 recruitment causes nucleosome repositioning and occlusion of Nrg1 binding sites. We suggest that nucleosome repositioning is the underlying mechanism for the yeast-hyphal transition. The hypha-specific regulator Ume6 is a key downstream target of Brg1 and functions after Brg1 as a built-in positive feedback regulator of the hyphal transcriptional program to sustain hyphal development. With the levels of Nrg1 and Brg1 dynamically and sensitively controlled by the two major cellular growth pathways, temporal changes in nucleosome positioning

  18. Secreted aspartic protease cleavage of Candida albicans Msb2 activates Cek1 MAPK signaling affecting biofilm formation and oropharyngeal candidiasis.

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    Sumant Puri

    Full Text Available Perception of external stimuli and generation of an appropriate response are crucial for host colonization by pathogens. In pathogenic fungi, mitogen activated protein kinase (MAPK pathways regulate dimorphism, biofilm/mat formation, and virulence. Signaling mucins, characterized by a heavily glycosylated extracellular domain, a transmembrane domain, and a small cytoplasmic domain, are known to regulate various signaling pathways. In Candida albicans, the mucin Msb2 regulates the Cek1 MAPK pathway. We show here that Msb2 is localized to the yeast cell wall and is further enriched on hyphal surfaces. A msb2Δ/Δ strain formed normal hyphae but had biofilm defects. Cek1 (but not Mkc1 phosphorylation was absent in the msb2Δ/Δ mutant. The extracellular domain of Msb2 was shed in cells exposed to elevated temperature and carbon source limitation, concomitant with germination and Cek1 phosphorylation. Msb2 shedding occurred differentially in cells grown planktonically or on solid surfaces in the presence of cell wall and osmotic stressors. We further show that Msb2 shedding and Cek1 phosphorylation were inhibited by addition of Pepstatin A (PA, a selective inhibitor of aspartic proteases (Saps. Analysis of combinations of Sap protease mutants identified a sap8Δ/Δ mutant with reduced MAPK signaling along with defects in biofilm formation, thereby suggesting that Sap8 potentially serves as a major regulator of Msb2 processing. We further show that loss of either Msb2 (msb2Δ/Δ or Sap8 (sap8Δ/Δ resulted in higher C. albicans surface β-glucan exposure and msb2Δ/Δ showed attenuated virulence in a murine model of oral candidiasis. Thus, Sap-mediated proteolytic cleavage of Msb2 is required for activation of the Cek1 MAPK pathway in response to environmental cues including those that induce germination. Inhibition of Msb2 processing at the level of Saps may provide a means of attenuating MAPK signaling and reducing C. albicans virulence.

  19. In vivo photodynamic inactivation of Candida albicans using chloro-aluminum phthalocyanine.

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    Carmello, J C; Alves, F; Ribeiro, Apd; Basso, F G; de Souza Costa, C A; Tedesco, A C; Primo, F L; Mima, E G; Pavarina, A C

    2016-07-01

    This study evaluated the photoinactivation of Candida albicans in a murine model of oral candidiasis using chloro-aluminum phthalocyanine (ClAlP) encapsulated in cationic nanoemulsions (NE) and chloro-aluminum phthalocyanine (ClAlP) diluted in DMSO (DMSO) as photosensitizer (PS). Seventy-five 6-week-old female Swiss mice were immunosuppressed and inoculated with C. albicans to induce oral candidiasis. PDT was performed on the tongue by the application of the photosensitizers and LED light (100 J cm(-2) -660 nm). Twenty-four hours and 7 days after treatments, microbiological evaluation was carried out by recovering C. albicans from the tongue of animals (CFU ml(-1) ). Then, mice were sacrificed and the tongues were surgically removed for histological and biomolecular analysis of pro- and anti-inflammatory cytokines. Data were analyzed by ANOVA followed by Tukey's post hoc test. ClAlP-NE-mediated PDT reduced 2.26 log10 of C. albicans recovered from the tongue when compared with the control group (P-L-) (P < 0.05). PDT did not promote adverse effects on the tongue tissue. Seven days after treatment, all animals were completely healthy. In summary, PDT mediated by chloro-aluminum phthalocyanine entrapped in cationic nanoemulsions was effective in reducing C. albicans recovered from the oral lesions of immunocompromised mice. PMID:26914185

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

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    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.

  1. 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.

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

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    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.

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

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    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.

  4. A comprehensive Candida albicans PeptideAtlas build enables deep proteome coverage.

    Science.gov (United States)

    Vialas, Vital; Sun, Zhi; Reales-Calderón, Jose A; Hernáez, María L; Casas, Vanessa; Carrascal, Montserrat; Abián, Joaquín; Monteoliva, Lucía; Deutsch, Eric W; Moritz, Robert L; Gil, Concha

    2016-01-10

    To provide new and expanded proteome documentation of the opportunistically pathogen Candida albicans, we have developed new protein extraction and analysis routines to provide a new, extended and enhanced version of the C. albicans PeptideAtlas. Two new datasets, resulting from experiments consisting of exhaustive subcellular fractionations and different growing conditions, plus two additional datasets from previous experiments on the surface and the secreted proteomes, have been incorporated to increase the coverage of the proteome. High resolution precursor mass spectrometry (MS) and ion trap tandem MS spectra were analyzed with three different search engines using a database containing allele-specific sequences. This approach, novel for a large-scale C. albicans proteomics project, was combined with the post-processing and filtering implemented in the Trans Proteomic Pipeline consistently used in the PeptideAtlas project and resulted in 49,372 additional peptides (3-fold increase) and 1630 more proteins (1.6-fold increase) identified in the new C. albicans PeptideAtlas with respect to the previous build. A total of 71,310 peptides and 4174 canonical (minimal non-redundant set) proteins (4115 if one protein per pair of alleles is considered) were identified representing 66% of the 6218 proteins in the predicted proteome. This makes the new PeptideAtlas build the most comprehensive C. albicans proteomics resource available and the only large-scale one with detections of individual alleles.

  5. 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.

  6. An Unusual Cause of Renal and Perirenal Abscesses: Candida albicans

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    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.

  7. Assessing the potential of four cathelicidins for the management of mouse candidiasis and Candida albicans biofilms.

    Science.gov (United States)

    Yu, Haining; Liu, Xuelian; Wang, Chen; Qiao, Xue; Wu, Sijin; Wang, Hui; Feng, Lan; Wang, Yipeng

    2016-02-01

    As the most common fungal pathogen of humans, severe drug resistance has emerged in the clinically isolated Candida albicans, which lead to the urgency to develop novel antifungal agents. Here, four our previously characterized cathelicidins (cathelicidin-BF, Pc-CATH1, Cc-CATH2, Cc-CATH3) were selected and their antifungal activities against C. albicans were evaluated in vitro and in vivo using amphotericin B and LL-37 as control. Results showed that all four cathelicidins could eradicate standard and clinically isolated C. albicans strains with most MIC values ranging from 1 to 16 μg/ml, in less than 0.5 h revealed by time-kill kinetic assay. Four peptides only exhibited slight hemolytic activity with most HC50 > 200 μg/ml, and retained potent anti-C. albicans activity at salt concentrations below and beyond physiological level. In animal experiment, 50 mg/kg administration of the four cathelicidins could significantly reduce the fungal counts in a murine oral candidiasis model induced by clinically isolated C. albicans. The antibiofilm activity of cathelicidin-BF, the most potent among the five peptides was evaluated, and result showed that cathelicidin-BF strongly inhibited C. albicans biofilm formation at 20 μg/ml. Furthermore, cathelicidin-BF also exhibited potent anti-C. albicans activity in established biofilms as measured by metabolic and fluorescent viability assays. Structure-function analyses suggest that they mainly adopt an α-helical conformations, which enable them to act as a membrane-active molecule. Altogether, the four cathelicidins display great potential for antifungal agent development against candidiasis. PMID:26656137

  8. 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.

  9. 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

  10. Candida albicans Gene Deletion with a Transient CRISPR-Cas9 System

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    Min, Kyunghun; Ichikawa, Yuichi

    2016-01-01

    ABSTRACT Clustered regularly interspaced short palindromic repeat (CRISPR) and CRISPR-associated gene 9 (CRISPR-Cas9) systems are used for a wide array of genome-editing applications in organisms ranging from fungi to plants and animals. Recently, a CRISPR-Cas9 system has been developed for the diploid fungal pathogen Candida albicans; the system accelerates genetic manipulation dramatically [V. K. Vyas, M. I. Barrasa, and G. R. Fink, Sci Adv 1(3):e1500248, 2015, http://dx.doi.org/10.1126/sciadv.1500248]. We show here that the CRISPR-Cas9 genetic elements can function transiently, without stable integration into the genome, to enable the introduction of a gene deletion construct. We describe a transient CRISPR-Cas9 system for efficient gene deletion in C. albicans. Our observations suggest that there are two mechanisms that lead to homozygous deletions: (i) independent recombination of transforming DNA into each allele and (ii) recombination of transforming DNA into one allele, followed by gene conversion of the second allele. Our approach will streamline gene function analysis in C. albicans, and our results indicate that DNA can function transiently after transformation of this organism. IMPORTANCE The fungus Candida albicans is a major pathogen. Genetic analysis of this organism has revealed determinants of pathogenicity, drug resistance, and other unique biological features, as well as the identities of prospective drug targets. The creation of targeted mutations has been greatly accelerated recently through the implementation of CRISPR genome-editing technology by Vyas et al. [Sci Adv 1(3):e1500248, 2015, http://dx.doi.org/10.1126/sciadv.1500248]. In this study, we find that CRISPR elements can be expressed from genes that are present only transiently, and we develop a transient CRISPR system that further accelerates C. albicans genetic manipulation. PMID:27340698

  11. 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

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

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    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.

  13. Genome-Wide Transposon Mutagenesis in Saccharomyces cerevisiae and Candida albicans

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    Xu, Tao; Bharucha, Nikë; Kumar, Anuj

    2016-01-01

    Transposon mutagenesis is an effective method for generating large sets of random mutations in target DNA, with applicability toward numerous types of genetic screens in prokaryotes, single-celled eukaryotes, and metazoans alike. Relative to methods of random mutagenesis by chemical/UV treatment, transposon insertions can be easily identified in mutants with phenotypes of interest. The construction of transposon insertion mutants is also less labor-intensive on a genome-wide scale than methods for targeted gene replacement, although transposon insertions are not precisely targeted to a specific residue, and thus coverage of the target DNA can be problematic. The collective advantages of transposon mutagenesis have been well demonstrated in studies of the budding yeast Saccharomyces cerevisiae and the related pathogenic yeast Candida albicans, as transposon mutagenesis has been used extensively for phenotypic screens in both yeasts. Consequently, we present here protocols for the generation and utilization of transposon-insertion DNA libraries in S. cerevisiae and C. albicans. Specifically, we present methods for the large-scale introduction of transposon insertion alleles in a desired strain of S. cerevisiae. Methods are also presented for transposon mutagenesis of C. albicans, encompassing both the construction of the plasmid-based transposon-mutagenized DNA library and its introduction into a desired strain of Candida. In total, these methods provide the necessary information to implement transposon mutagenesis in yeast, enabling the construction of large sets of identifiable gene disruption mutations, with particular utility for phenotypic screening in nonstandard genetic backgrounds. PMID:21815095

  14. Population Structure of Candida albicans from Three Teaching Hospitals in Ghana.

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    Adjapong, Gloria; Hale, Marie; Garrill, Ashley

    2016-02-01

    Previous studies on Candida species in a clinical setting in Ghana have shown a prevalence of Candida albicans. Despite this, very little is known about the various strain types and their population genetic structure. In this study three microsatellite loci, CAI, CAIII and CAVI, were used to investigate the population genetic structure of C. albicans from clinical isolates in Ghana. In all, 240 clinically unrelated C. albicans isolates were recovered from patients reporting at three teaching hospitals. All the isolates were heterozygous for at least one of the three loci, except for one isolate, which was homozygous for all three loci. Sixty-seven unique alleles and 240 different genotypes were generated by the three polymorphic microsatellite loci, resulting in a very high discriminatory potential of approximately 0.98. There was no significant difference in allele frequencies from the small number of anatomical sites sampled, regardless of the host conditions although high genotypic diversities were observed among the isolates. There was evidence for clonal reproduction, including over-expression of observed heterozygotes across the populations. The populations deviated significantly from Hardy-Weinberg equilibrium and pair-wise genotypic linkage disequilibria comparisons across the three loci were significant, also suggesting a clonal population. The overall Wright FIS for the three loci was negative, and the overall FST value was not significantly different from zero for the three loci analyzed, indicating a clonal and homogeneous population across the three sampling locations from Ghana.

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

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    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.

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

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    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

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

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    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.

  18. 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

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

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    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

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

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    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.

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

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    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.

  2. Cellular Structural Changes in Candida albicans Caused by the Hydroalcoholic Extract from Sapindus saponaria L.

    Science.gov (United States)

    Shinobu-Mesquita, Cristiane S; Bonfim-Mendonça, Patricia S; Moreira, Amanda L; Ferreira, Izabel C P; Donatti, Lucelia; Fiorini, Adriana; Svidzinski, Terezinha I E

    2015-01-01

    Vulvovaginal candidiasis (VVC) is a disease caused by the abnormal growth of yeast-like fungi in the mucosa of the female genital tract. Candida albicans is the principal etiological agent involved in VVC, but reports have shown an increase in the prevalence of Candida non-C. albicans (CNCA) cases, which complicates VVC treatment because CNCA does not respond well to antifungal therapy. Our group has reported the in vitro antifungal activity of extracts from Sapindus saponaria L. The present study used scanning electron microscopy and transmission electron microscopy to further evaluate the antifungal activity of hydroalcoholic extract from S. saponaria (HE) against yeast obtained from VVC and structural changes induced by HE. We observed the antifungal activity of HE against 125 vaginal yeasts that belonged to four different species of the Candida genus and S. cerevisae. The results suggest that saponins that are present in HE act on the cell wall or membrane of yeast at the first moments after contact, causing damage to these structures and cell lysis. PMID:26007191

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

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    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.

  4. 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

  5. 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.

  6. Assessment of antifungal activity of herbal and conventional toothpastes against clinical isolates of Candida albicans

    Institute of Scientific and Technical Information of China (English)

    Ghaleb Adwan; Yousef Salameh; Kamel Adwan; Ali Barakat

    2012-01-01

    Objective: To detect the anticandidal activity of nine toothpastes containing sodium fluoride, sodium monofluorophosphate and herbal extracts as an active ingredients against 45 oral and non oral Candida albicans (C. albicans) isolates. Methods: The antifungal activity of these toothpaste formulations was determined using a standard agar well diffusion method. Statistical analysis was performed using a statistical package, SPSS windows version 15, by applying mean values using one-way ANOVA with post-hoc least square differences (LSD) method. A P value of less than 0.05 was considered significant. Results: All toothpastes studied in our experiments were effective in inhibiting the growth of all C. albicans isolates. The highest anticandidal activity was obtained from toothpaste that containing both herbal extracts and sodium fluoride as active ingredients, while the lowest activity was obtained from toothpaste containing sodium monofluorophosphate as an active ingredient. Antifungal activity of Parodontax toothpaste showed a significant difference (P< 0.001) against C. albicans isolates compared to toothpastes containing sodium fluoride or herbal products. Conclusions: In the present study, it has been demonstrated that toothpaste containing both herbal extracts and sodium fluoride as active ingredients are more effective in control of C. albicans, while toothpaste that containing monofluorophosphate as an active ingredient is less effective against C. albicans. Some herbal toothpaste formulations studied in our experiments, appear to be equally effective as the fluoride dental formulations and it can be used as an alternative to conventional formulations for individuals who have an interest in naturally-based products. Our results may provide invaluable information for dental professionals.

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

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    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.

  8. Antifungal properties of Foeniculum vulgare, Carum carvi and Eucalyptus sp. essential oils against Candida albicans strains

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    Skrobonja Jelica M.

    2013-01-01

    Full Text Available Aromatic plants are among the most important sources of biologically active secondary metabolites, with high antimicrobal potential. This study was carried out to examine in vitro antifungal activity of Foeniculum vulgare (Apiaceae, Carum carvi (Apiaceae and Eucalyptus sp.(Myrtaceae essential oils against three Candida albicans strains of different origin (laboratory-CAL, human pulmonary-CAH and ATCC10231-CAR. The essential oils were screened on C. albicans using disc and well-diffusion and microdilution method, and compared to Nystatine and Fluconazole as standard anti-mycotics. The activity of tested oils was expressed by inhibition zone diameter (mm, minimum inhibitory concentration (MIC and minimum fungicidal concentration (MFC (mg/ml. The results indicated that studied essential oils show antifungal activity against all three isolates of C. albicans. It was observed that each oil exhibits different degree of antifungal activity depending on the oil concentration applied as well as on analyzed strain of C. albicans. Carum carvi demonstrated the strongest antifungal effect to all tested strains, showing the lowest MIC values (0.03mg/ml for CAL, 0.06mg/ml for CAH, and 0.11mg/ml for CAR, respectively. Eucalyptus sp. exhibited the lowest antifungal activity, with MIC values ranging from 0.11 mg/ml for CAL to 0.45 mg/ml for both CAH and CAR. [Projekat Ministarstva nauke Republike Srbije, br. 172058

  9. Genome-Wide Synthetic Genetic Screening by Transposon Mutagenesis in Candida albicans

    Science.gov (United States)

    Horton, Brooke N.; Kumar, Anuj

    2016-01-01

    Transposon-based mutagenesis is an effective method for genetic screening on a genome-wide scale, with particular applicability in organisms possessing compact genomes where transforming DNA tends to integrate by homologous recombination. Methods for transposon mutagenesis have been applied with great success in the budding yeast Saccharomyces cerevisiae and in the related pathogenic yeast Candida albicans. In C. albicans, we have implemented transposon mutagenesis to generate heterozygous mutations for the analysis of complex haploinsufficiency, a type of synthetic genetic interaction wherein a pair of non-complementing heterozygous mutations results in a stronger phenotype then either individual mutation in isolation. Genes exhibiting complex haploinsufficiency typically function within a regulatory pathway, in parallel pathways, or in parallel branches within a single pathway. Here, we present protocols to implement transposon mutagenesis for complex haploinsufficiency screening in C. albicans, indicating methods for transposon construction, mutagenesis, phenotypic screening, and identification of insertion sites in strains of interest. In total, the approach is a useful means to implement large-scale synthetic genetic screening in the diploid C. albicans. PMID:25636616

  10. Induction of the immune response suppression in mice inoculated with Candida albicans.

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    Valdez, J C; Mesón, D E; Sirena, A; de Petrino, S F; Eugenia, M; de Jorrat, B B; de Valdex, M G

    1986-03-01

    There is a controversy in respect to the immunological response (humoral or cellular) concerning the defense against Candida albicans. Candidosis would induce sub-populations of suppressor cells in the host cell-immune response. This report tries to show the effect of different doses of C. albicans (alive or heat-killed) on the expression of cell-mediated and humoral immunity. The effect upon cell immunity was determined by inoculating different lots of singeneic mice, doses of varied concentration of C. albicans and checking for delayed-type hipersensitivity (D.T.H.). D.T.H. was also controlled in syngeneic normal mice which had previously been injected with inoculated mice spleen cells. Humoral immunity was assayed by measuring the induced blastogenesis by Pokeweed Mitogen on spleen mononuclear cells with different doses of C. albicans. Results obtained show that the different doses gave origin to: Suppression of humoral and cell response (10(8) alive); Suppression of only humoral response (10(6) alive); Suppression of cell response and increase of humoral response (10(9) dead); Increase of both responses (10(8) dead).

  11. 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

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

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    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.

  13. 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.

  14. Antifungal activity, kinetics and molecular mechanism of action of garlic oil against Candida albicans.

    Science.gov (United States)

    Li, Wen-Ru; Shi, Qing-Shan; Dai, Huan-Qin; Liang, Qing; Xie, Xiao-Bao; Huang, Xiao-Mo; Zhao, Guang-Ze; Zhang, Li-Xin

    2016-01-01

    The antifungal activity, kinetics, and molecular mechanism of action of garlic oil against Candida albicans were investigated in this study using multiple methods. Using the poisoned food technique, we determined that the minimum inhibitory concentration of garlic oil was 0.35 μg/mL. Observation by transmission electron microscopy indicated that garlic oil could penetrate the cellular membrane of C. albicans as well as the membranes of organelles such as the mitochondria, resulting in organelle destruction and ultimately cell death. RNA sequencing analysis showed that garlic oil induced differential expression of critical genes including those involved in oxidation-reduction processes, pathogenesis, and cellular response to drugs and starvation. Moreover, the differentially expressed genes were mainly clustered in 19 KEGG pathways, representing vital cellular processes such as oxidative phosphorylation, the spliceosome, the cell cycle, and protein processing in the endoplasmic reticulum. In addition, four upregulated proteins selected after two-dimensional fluorescence difference in gel electrophoresis (2D-DIGE) analysis were identified with high probability by mass spectrometry as putative cytoplasmic adenylate kinase, pyruvate decarboxylase, hexokinase, and heat shock proteins. This is suggestive of a C. albicans stress responses to garlic oil treatment. On the other hand, a large number of proteins were downregulated, leading to significant disruption of the normal metabolism and physical functions of C. albicans. PMID:26948845

  15. New pFA-cassettes for PCR-based gene manipulation in Candida albicans.

    Science.gov (United States)

    Schaub, Yvonne; Dünkler, Alexander; Walther, Andrea; Wendland, Jürgen

    2006-01-01

    Several modules for efficient PCR-based gene disruption have recently been introduced in Candida albicans. These are based on auxotrophic marker genes for deficient strains derived from SC5314/CAI4. Commonly used protocols for the transformation C. albicans are based either on the lithium acetate procedure or on electroporation also used for Saccharomyces cerevisiae. Here we present our updated arsenal of pFA-modules that now include the heterologous marker genes HIS1 from C. dubliniensis and LEU2 from C. maltosa (Noble and Johnson 2005) and the dominant selection marker ca SAT1 (Reuss et al. 2004). We also introduce the Ashbya gossypii TEF1 -promoter as a strong constitutive promoter. With these new elements an enlarged collection of pFA-marker and pFA-marker-promoter modules were generated containing 17 new modules. In addition, N-terminal tagging with GFP-(GA) 6 and epitope-tagging modules using the 6 x-HIS-tag were constructed. This adds to the previous modules that only enabled C-terminal GFP-tagging of genes (Gola et al. 2003). In total 29 pFA-modules are currently freely available from our lab which - together with an update on the diagnostic verification procedure - further enlarge the C. albicans molecular toolbox and enhance our capabilities to use PCR-based gene alteration methods in C. albicans. PMID:17009297

  16. Relationship between antifungal resistance of fluconazole resistant Candida albicans and mutations in ERG11 gene

    Institute of Scientific and Technical Information of China (English)

    FENG Li-juan; WAN Zhe; WANG Xiao-hong; LI Ruo-yu; LIU Wei

    2010-01-01

    Background The cytochrome P450 lanosterol 14α-demethylase(Erg11p) encoded by ERG11 gene is the primary target for azole antifungals.Changes in azole affinity of this enzyme caused by amino acid substitutions have been reported as a mechanism of azole antifungal resistance. This study aimed to investigate the relationship between amino acid substitutions in Erg11p from fluconazole resistant Candida albicans (C.albicans)isolates and their cross-resistance to azoles.Methods Mutations in ERG11 gene were screened in 10 clinical isolates of fluconazole resistant C.albicans strains.DNA sequence of ERG11 was determined by PCR based DNA sequencing.Results In the 10 isolates,19 types of amino acid substitutions were found,of which 10 substitutions (F72S, F103L, F145I, F198L, G206D, G227D, N349S, F416S, F422L and T482A) have not been reported previously. Mutations in ERG11 gene were detected in 9 isolates of fluconazole resistant C. albicans, but were not detected in 1 isolate. Conclusions Although no definite correlation was found between the type of amino acid substitutions in Erg11p and the phenotype of cross-resistance to azoles, the substitutions F72S, F145I and G227D in our study may be highly associated with resistance to azoles because of their special location in Erg11p.

  17. 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.

  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. PMID:26902505

  19. 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

  20. Antimicrobial effects of Piper hispidum extract, fractions and chalcones against Candida albicans and Staphylococcus aureus.

    Science.gov (United States)

    Costa, G M; Endo, E H; Cortez, D A G; Nakamura, T U; Nakamura, C V; Dias Filho, B P

    2016-09-01

    Three chalcones, 2'-hydroxy-4,4',6'-trimethoxychalcone, 2'-hydroxy-4,4',6'-tetramethoxychalcone, and 3,2'-dihydroxy-4,4',6'-trimethoxychalcone, were isolated from the leaves of Piper hispidum in a bioguided fractionation of crude extract. The antimicrobial activity of crude extract of P. hispidum leaves was determined against bacteria Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, Staphylococcus aureus and yeasts Candida albicans, C. parapsilosis and C. tropicalis. Fractions and chalcones were tested against C. albicans and S. aureus. The checkerboard assay was performed to assess synergic interactions between extract and antifungal drugs, and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction assay was used to evaluate anti-biofilm effects of extract. The extract was active against yeasts, S. aureus and B. subtilis with MIC values between 15.6 and 62.5μg/mL. Synergistic effects of extract associated with fluconazole and nystatin were observed against C. albicans, with fractional inhibitory concentration indices of 0.37 and 0.24, respectively. The extract was also effective against C. albicans and S. aureus biofilm cells at concentrations of 62.5 and 200μg/mL, respectively. Thus, P. hispidum may be a possible source of bioactive substances with antimicrobial properties. PMID:27499460

  1. 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.

  2. A conserved mitogen-activated protein kinase pathway is required for mating in Candida albicans.

    Science.gov (United States)

    Chen, Jiangye; Chen, Jing; Lane, Shelley; Liu, Haoping

    2002-12-01

    Candida albicans had been thought to lack a mating process until the recent discovery of a mating type-like locus and mating between MTLa and MTL(alpha) strains. To elucidate the molecular mechanisms that regulate mating in C. albicans, we examined the function of Cph1 and its upstream mitogen-activated protein (MAP) kinase pathway in mating, as they are homologues of the pheromone-responsive MAP kinase pathway in Saccharomyces cerevisiae. We found that overexpressing CPH1 in MTLa, but not in MTLa/alpha strains, induced the transcription of orthologues of S. cerevisiae pheromone-induced genes and also increased mating efficiency. Furthermore, cph1 and hst7 mutants were completely defective in mating, and cst20 and cek1 mutants showed reduced mating efficiency, as in S. cerevisiae. The partial mating defect in cek1 results from the presence of a functionally redundant MAP kinase, Cek2. CEK2 complemented the mating defect of a fus3 kss1 mutant of S. cerevisiae and was expressed only in MTLa or MTL(alpha), but not in MTLa/alpha cell types. Moreover, a cek1 cek2 double mutant was completely defective in mating. Our data suggest that the conserved MAP kinase pathway regulates mating in C. albicans. We also observed that C. albicans mating efficiency was greatly affected by medium composition, indicating the potential involvement of nutrient-sensing pathways in mating in addition to the MAP kinase pathway. PMID:12453219

  3. 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.

  4. 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.

  5. Bioactivity of a Family of Chiral Nonracemic Aminobenzylnaphthols towards Candida albicans

    Directory of Open Access Journals (Sweden)

    Maria Annunziata M. Capozzi

    2014-04-01

    Full Text Available Chiral nonracemic aminobenzylnaphthols were obtained by a Betti multi-component reaction between 2-naphthol, aryl aldehydes and enantiopure arylethylamine. Moreover, some new aminobenzylnaphthols were synthesized by a similar reaction between 2-naphthol, aryl aldehydes and prolinol. These aminobenzylnaphthols, synthesized from different components and thus having different structural features, were tested as anti-yeast agents inhibiting Candida albicans. The effect towards the test strain was studied with a microdilution approach and three different concentrations (150, 300 and 450 µg/mL were tested. The best results were found for the aminobenzylnaphthols obtained from 1-naphthylethylamine and from natural prolinol. The use of the two-way ANOVA highlighted the better performances of the prolinol derivative among the differently structured aminobenzylnaphthols that were screened. The activity towards C. albicans of this prolinol derivative resulted to be interesting and could represent a promising alternative to overcome the problem of the strains resistant to the traditional antifungals.

  6. 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.

  7. 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.

  8. Thiamin Pyrimidine Biosynthesis in Candida albicans: A Remarkable Reaction between Histidine and Pyridoxal Phosphate

    Energy Technology Data Exchange (ETDEWEB)

    Lai, Rung-Yi; Huang, Siyu; Fenwick, Michael K.; Hazra, Amrita; Zhang, Yang; Rajashankar, Kanagalaghatta; Philmus, Benjamin; Kinsland, Cynthia; Sanders, Jennie Mansell; Ealick, Steven E.; Begley, Tadhg P. (Cornell); (TAM)

    2012-06-26

    In Saccharomyces cerevisiae, thiamin pyrimidine is formed from histidine and pyridoxal phosphate (PLP). The origin of all of the pyrimidine atoms has been previously determined using labeling studies and suggests that the pyrimidine is formed using remarkable chemistry that is without chemical or biochemical precedent. Here we report the overexpression of the closely related Candida albicans pyrimidine synthase (THI5p) and the reconstitution and preliminary characterization of the enzymatic activity. A structure of the C. albicans THI5p shows PLP bound at the active site via an imine with Lys62 and His66 in close proximity to the PLP. Our data suggest that His66 of the THI5 protein is the histidine source for pyrimidine formation and that the pyrimidine synthase is a single-turnover enzyme.

  9. 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

  10. 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

  11. 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

  12. Biofilms of Candida albicans serotypes A and B differ in their sensitivity to photodynamic therapy.

    Science.gov (United States)

    Rossoni, Rodnei Dennis; Barbosa, Júnia Oliveira; de Oliveira, Felipe Eduardo; de Oliveira, Luciane Dias; Jorge, Antonio Olavo Cardoso; Junqueira, Juliana Campos

    2014-09-01

    Candida albicans is classified into different serotypes according to cell wall mannan composition and cell surface hydrophobicity. Since the effectiveness of photodynamic therapy (PDT) depends on the cell wall structure of microorganisms, the objective of this study was to compare the sensitivity of in vitro biofilms of C. albicans serotypes A and B to antimicrobial PDT. Reference strains of C. albicans serotype A (ATCC 36801) and serotype B (ATCC 36802) were used for the assays. A gallium-aluminum-arsenide laser (660 nm) was used as the light source and methylene blue (300 μM) as the photosensitizer. After biofilm formation on the bottom of a 96-well microplate for 48 h, each Candida strain was submitted to assays: PDT consisting of laser and photosensitizer application (L + P+), laser application alone (L + P-), photosensitizer application alone (L-P+), and application of saline as control (L-P-). After treatment, biofilm cells were scraped off and transferred to tubes containing PBS. The content of the tubes was homogenized, diluted, and seeded onto Sabouraud agar plates to determine the number of colony-forming units (CFU/mL). The results were compared by analysis of variance and Tukey test (p < 0.05). The two strains studied were sensitive to PDT (L + P+), with a log reduction of 0.49 for serotype A and of 2.34 for serotype B. Laser application alone only reduced serotype B cells (0.53 log), and the use of the photosensitizer alone had no effect on the strains tested. It can be concluded that in vitro biofilms of C. albicans serotype B were more sensitive to PDT.

  13. Cyclosporine A decreases the fluconazole minimum inhibitory concentration of Candida albicans clinical isolates but not biofilm formation and cell growth.

    Science.gov (United States)

    Wibawa, T; Nurrokhman; Baly, I; Daeli, P R; Kartasasmita, G; Wijayanti, N

    2015-03-01

    Among the genus Candida, Candida albicans is the most abundant species in humans. One of the virulent factors of C. albicans is its ability to develop biofilm. Biofilm forming microbes are characterized by decreasing of its susceptibility to antibiotics and antifungal. The fungicidal effect of fluconazole may be enhanced by cyclosporine A in laboratory engineered C. albicans strains. The aim of this work is to analyze the synergistic effect of cyclosporine A with fluconazole in C. albicans clinical isolates and the effect of cycolsporine A alone in the biofilm formation. Six fluconazole resistant and six sensitive C. albicans clinical isolates were analyzed for its minimum inhibitory concentration (MICs), biofilm formation, and cell growths. A semi-quantitative XTT [2,3-bis(2-methoxy-4-nitro-5- sulfo-phenyl)-2H-tetrazolium-5-carboxanilide] reduction assay was conducted to measure the biofilm formation. Cyclosporine A has synergistic effect with fluconazole that was shown by decreasing MICs of both fluconazole resistant and sensitive C. albicans clinical isolates. However, cyclosporine A alone did not influence the biofilm formation and cell growth of both fluconazole resistant and sensitive C. albicans clinical isolates. These results indicated that cyclosporine A might be a promising candidate of adjuvant therapy for fluconazole against both fluconazole resistant and sensitive C. albicans clinical isolates.

  14. CHARACTERISTIC OF SENSITIVITY OF STAPHYLOCOCCUS AUREUS AND CANDIDA ALBICANS TO ANTIBACTERIAL PREPARATIONS AND COLLOIDAL SILVER

    Directory of Open Access Journals (Sweden)

    I. A. Afonina

    2011-01-01

    Full Text Available Abstract. Constant use of antibiotics leads to reliable increasing of resistance among microorganisms. Using non-toxic concentrations of colloidal silver in combination with antimicrobial agents can reduce using concentrations of antibiotics, kept necessary antimicrobial effect. In case of Staphylococcus aureus bactericidal activity of the complex of colloidal silver with unit concentration of neomycin is bigger than the bactericidal effect of double concentration of the antibiotic. Fungicidal effect of combination of antifungal agents with a solution of the colloidal silver on Candida albicans is equal to fungicidal effect of double concentration of antifungal drugs.

  15. Azole Binding Properties of Candida albicans Sterol 14-α Demethylase (CaCYP51)▿

    OpenAIRE

    Warrilow, Andrew G. S.; Martel, Claire M.; Parker, Josie E.; Melo, Nadja; Lamb, David C.; Nes, W. David; Kelly, Diane E.; Kelly, Steven L.

    2010-01-01

    Purified Candida albicans sterol 14-α demethylase (CaCYP51) bound the CYP51 substrates lanosterol and eburicol, producing type I binding spectra with Ks values of 11 and 25 μM, respectively, and a Km value of 6 μM for lanosterol. Azole binding to CaCYP51 was “tight” with both the type II spectral intensity (ΔAmax) and the azole concentration required to obtain a half-ΔAmax being proportional to the CaCYP51 concentration. Tight binding of fluconazole and itraconazole was confirmed by 50% inhib...

  16. Impact of Low Frequency Electromagnetic Field Exposure on the Candida Albicans

    Science.gov (United States)

    Malíková, Ivona; Janoušek, Ladislav; Fantova, Vladyslava; Jíra, Jaroslav; Kříha, Vítĕzslav

    2015-03-01

    Effect of low frequency electromagnetic field on growth of selected microorganism is studied in the article. The diploid fungus that grows both as yeast and filamentous cell was chosen for this research. The theory of ion parametric resonance was taken as the base for studying the influence of electromagnetic field on biological structures. We tested the hypothesis, whether it is possible to observe the change in growth properties of Candida albicans with an AC electromagnetic field tuned to resonance with calcium ions cyclotron frequency.

  17. Evaluation of the genotoxic and mutagenic potentials of homeopathic Candida albicans solutions

    Directory of Open Access Journals (Sweden)

    André Luis Santos

    2011-09-01

    Full Text Available Background: Candida spp is naturally found in humans’ flora of skin, gastrointestinal and genitourinary tracts and, in general, up to 75% of the population does not have any symptom [1]. However, oral candidiasis is very common among HIV patients and patients undergoing chemotherapy. The treatment of oral candidiasis is necessary once the disease causes discomfort and dysphagia, resulting in poor nutrition, slow recovery, and prolonged hospital stay [2,3]. Preliminary results obtained by our group with a new biotherapic prepared from Candida albicans (Candida 30x showed a great potential to reduce the candida yeast adhesion rate when the epithelial cells were pre-treated. This study is currently being developed with the evaluation of mutagenic and genotoxic potentials of several homeopathic solutions. Aims: The goal of this study was to assess the genotoxic and mutagenic potentials of different homeopathic potencies of C. albicans. Methodology: One part of C. albicans yeast obtained from Brazilian patient’s blood [4] was diluted in 9 parts of sterile water. This sample was submitted to 100 mechanical succussions (approximately 3 Hz, using Autic® Brazilian machine, originating the first dilution (1x. Then, 1 ml of this solution was diluted in 9 ml of solvent, submitted to 100 succussions, obtaining 2x potency. This procedure was successively repeated to obtain 30x potency, according to Brazilian Homeopathic Pharmacopoeia [5]. By the same technique, water vehicle was prepared until 30x to be used as control. All samples were prepared in sterile and aseptic conditions, using laminar flow cabinet, class II and were stored in the refrigerator (8ºC. The samples 1x, 6x, 12x, 18x, 24x and 30x of C. albicans and water 30x (vehicle control were analysed by: the Inductest, which assesses the ability of physical or chemical agents to promote lysogenic induction as a reflection of damage in DNA

  18. SLA2 mutations cause SWE1-mediated cell cycle phenotypes in Candida albicans and Saccharomyces cerevisiae

    OpenAIRE

    Gale, Cheryl A.; Leonard, Michelle D.; Finley, Kenneth R.; Christensen, Leah; McClellan, Mark; Abbey, Darren; Kurischko, Cornelia; Bensen, Eric; Tzafrir, Iris; Kauffman, Sarah; Becker, Jeff; Berman, Judith

    2009-01-01

    The early endocytic patch protein Sla2 is important for morphogenesis and growth rates in Saccharomyces cerevisiae and Candida albicans, but the mechanism that connects these processes is not clear. Here we report that growth defects in cells lacking CaSLA2 or ScSLA2 are associated with a cell cycle delay that is influenced by Swe1, a morphogenesis checkpoint kinase. To establish how Swe1 monitors Sla2 function, we compared actin organization and cell cycle dynamics in strains lacking other c...

  19. Inhibitory activity of root canal irrigants against Candida albicans, Enterococcus faecalis and Staphylococcus aureus

    OpenAIRE

    Tatiana Kelly da Silva Fidalgo; Roberta Barcelos; Maristela Barbosa Portela; Rosangela Maria de Araújo Soares; Rogério Gleiser; Fernando Costa e Silva-Filho

    2010-01-01

    The present study evaluated the antimicrobial activity of three root canal irrigants against Enterococcus faecalis, Candida albicans, and Staphylococcus aureus. These microorganisms were incubated in the presence of citric acid (6 and 10%), EDTA (17%), and NaOCl (0.5, 1.0, 2.5, and 5.25%). Agar diffusion tests were performed and redox indicator resazurin was used to evaluate the inhibitory effect of the irrigants on the metabolic activity of these microorganisms. The mean diameters of the inh...

  20. Iron-Limited Biofilms of Candida albicans and Their Susceptibility to Amphotericin B

    OpenAIRE

    Baillie, George S.; Douglas, L. Julia

    1998-01-01

    Biofilms of Candida albicans were grown in vitro under iron limitation and at a low growth rate to simulate conditions for implant-associated biofilms in vivo. Their properties were compared with those of glucose-limited biofilms grown under analogous conditions. At steady state, the adherent cell populations of iron-limited biofilms were double those of glucose-limited biofilms, although the growth rates were similar (0.038 to 0.043 h−1). Both biofilm types were resistant to amphotericin B, ...

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

    Directory of Open Access Journals (Sweden)

    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.

  2. 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....

  3. Analysis of a solid-phase radioimmunoassay for antibodies to cytoplasmic antigen fractions of Candida albicans

    International Nuclear Information System (INIS)

    An indirect solid-phase radioimmunoassay (SPRIA) in individual polystyrene microtiter cups has been adapted for measurement of antibody to various cytoplasmic and carbohydrate antigen fractions of Candida albicans. The assay was optimized for sensitivity, precision and linearization of serum dilution curves. The optimized procedure allows computerized measurement of anti-Candida antibodies and can be used for measurement of antibody over a wide concentration range. The procedure obviates variation due to changes in day-to-day counts as a result of isotope decay and end-point antibody dilutions. The assay has been used to demonstrate a Poisson-like distribution of antibody levels in the sera of persons showing no symptoms of candidiasis. The minimum antibody level detectable by the assay is about two orders of magnitude lower than the lowest level found in human serum and 4 orders of magnitude lower than the most sensitive test used hitherto, the hemagglutination test. (Auth.)

  4. 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...

  5. Phospholipase, proteinase and haemolytic activities of Candida albicans isolated from oral cavities of patients with type 2 diabetes mellitus

    OpenAIRE

    Tsang, CSP; Chu, FCS; Leung, WK; Jin, LJ; Samaranayake, LP; Siu, SC

    2007-01-01

    The aim of this study was to biotype and characterize phospholipase, proteinase and haemolytic activities of oral Candida albicans isolates from 210 Chinese patients with type 2 diabetes mellitus (DM) and 210 age- and sex-matched healthy controls. Seventy-six and 50 C. albicans isolates were obtained from type 2 DM patients and controls, respectively, using the oral rinse technique. The isolates were characterized with a biotyping system based on enzyme profiles, carbohydrate assimilation pat...

  6. Immune sensing of Candida albicans requires cooperative recognition of mannans and glucans by lectin and Toll-like receptors

    OpenAIRE

    Netea, M.G.; Gow, N.A.; Munro, C.A.; S. Bates; Collins, C; Ferwerda, G.; HOBSON, R. P.; Bertram, G; Hughes, H.B.; Jansen, T.; Jacobs, L; Buurman, E.T.; Gijzen, K.; Williams, D. L.; Torensma, R.

    2006-01-01

    The fungal pathogen Candida albicans has a multilayered cell wall composed of an outer layer of proteins glycosylated with N- or O-linked mannosyl residues and an inner skeletal layer of β-glucans and chitin. We demonstrate that cytokine production by human mononuclear cells or murine macrophages was markedly reduced when stimulated by C. albicans mutants defective in mannosylation. Recognition of mannosyl residues was mediated by mannose receptor binding to N-linked mannosyl residues and by ...

  7. Design of a Simple Model of Candida albicans Biofilms Formed under Conditions of Flow: Development, Architecture and Drug Resistance

    OpenAIRE

    Uppuluri, Priya; Chaturvedi, Ashok K.; Ribot, Jose Lopez

    2009-01-01

    Candida albicans biofilms on most medical devices are exposed to a flow of body fluids that provide water and nutrients to the fungal cells. While C. albicans biofilms grown in vitro under static conditions have been exhaustively studied, the same is not true for biofilms developed under continuous flow of replenishing nutrients. Here, we describe a simple flow biofilm (FB) model that can be built easily with materials commonly available in most microbiological laboratories. We demonstrate th...

  8. 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...

  9. Inducible and Constitutive Activation of Two Polymorphic Promoter Alleles of the Candida albicans Multidrug Efflux Pump MDR1

    OpenAIRE

    Sasse, Christoph; Schillig, Rebecca; Reimund, Alexandra; Merk, Julia; Morschhäuser, Joachim

    2012-01-01

    Overexpression of the multidrug efflux pump MDR1 confers resistance to the antifungal drug fluconazole on Candida albicans. It has been reported that two types of MDR1 promoters exist in C. albicans and that homozygosity for the allele with higher activity may promote fluconazole resistance. We found that the two MDR1 promoter alleles in strain SC5314 were equally well activated by inducing chemicals or hyperactive forms of the transcription factors Mrr1 and Cap1, which control MDR1 expressio...

  10. Calcineurin signaling and membrane lipid homeostasis regulates iron mediated multidrug resistance mechanisms in Candida albicans.

    Directory of Open Access Journals (Sweden)

    Saif Hameed

    Full Text Available We previously demonstrated that iron deprivation enhances drug susceptibility of Candida albicans by increasing membrane fluidity which correlated with the lower expression of ERG11 transcript and ergosterol levels. The iron restriction dependent membrane perturbations led to an increase in passive diffusion and drug susceptibility. The mechanisms underlying iron homeostasis and multidrug resistance (MDR, however, are not yet resolved. To evaluate the potential mechanisms, we used whole genome transcriptome and electrospray ionization tandem mass spectrometry (ESI-MS/MS based lipidome analyses of iron deprived Candida cells to examine the new cellular circuitry of the MDR of this pathogen. Our transcriptome data revealed a link between calcineurin signaling and iron homeostasis. Among the several categories of iron deprivation responsive genes, the down regulation of calcineurin signaling genes including HSP90, CMP1 and CRZ1 was noteworthy. Interestingly, iron deprived Candida cells as well as iron acquisition defective mutants phenocopied molecular chaperone HSP90 and calcineurin mutants and thus were sensitive to alkaline pH, salinity and membrane perturbations. In contrast, sensitivity to above stresses did not change in iron deprived DSY2146 strain with a hyperactive allele of calcineurin. Although, iron deprivation phenocopied compromised HSP90 and calcineurin, it was independent of protein kinase C signaling cascade. Notably, the phenotypes associated with iron deprivation in genetically impaired calcineurin and HSP90 could be reversed with iron supplementation. The observed down regulation of ergosterol (ERG1, ERG2, ERG11 and ERG25 and sphingolipid biosynthesis (AUR1 and SCS7 genes followed by lipidome analysis confirmed that iron deprivation not only disrupted ergosterol biosynthesis, but it also affected sphingolipid homeostasis in Candida cells. These lipid compositional changes suggested extensive remodeling of the membranes in iron

  11. [Electron microscopic presentation of immune reactions on Candida cells: asteroid bodies in Candida albicans from the urine of nephritis patients].

    Science.gov (United States)

    Müller, J; Takamiya, H; Jaeger, R

    1977-03-01

    Candida albicans cells from the urine of two nephritis patients were concentrated and incubated with ferritin-labeled antihuman grammaglobulin (either anti-IgA, anti-IgG, or anti-IgM). Electron microscopy showed the electron-transparent yeast cell wall to be surrounded by an electron-dense capsule-like substance of remarkable volume. This must be regarded as an antigen-antibody precipitate corresponding to the "asteroid body" of previous authors. The antibodies involved in the formation of the precipitate are mainly those of the IgA and IgG classes. Considering the results of previous authors, the following definition is proposed: "Asteroid Bodies" are light microscopically visible antigen-antibody precipitates on the cell wall of fungi parasitic condition.

  12. Integration of Posttranscriptional Gene Networks into Metabolic Adaptation and Biofilm Maturation in Candida albicans.

    Directory of Open Access Journals (Sweden)

    Jiyoti Verma-Gaur

    2015-10-01

    Full Text Available The yeast Candida albicans is a human commensal and opportunistic pathogen. Although both commensalism and pathogenesis depend on metabolic adaptation, the regulatory pathways that mediate metabolic processes in C. albicans are incompletely defined. For example, metabolic change is a major feature that distinguishes community growth of C. albicans in biofilms compared to suspension cultures, but how metabolic adaptation is functionally interfaced with the structural and gene regulatory changes that drive biofilm maturation remains to be fully understood. We show here that the RNA binding protein Puf3 regulates a posttranscriptional mRNA network in C. albicans that impacts on mitochondrial biogenesis, and provide the first functional data suggesting evolutionary rewiring of posttranscriptional gene regulation between the model yeast Saccharomyces cerevisiae and C. albicans. A proportion of the Puf3 mRNA network is differentially expressed in biofilms, and by using a mutant in the mRNA deadenylase CCR4 (the enzyme recruited to mRNAs by Puf3 to control transcript stability we show that posttranscriptional regulation is important for mitochondrial regulation in biofilms. Inactivation of CCR4 or dis-regulation of mitochondrial activity led to altered biofilm structure and over-production of extracellular matrix material. The extracellular matrix is critical for antifungal resistance and immune evasion, and yet of all biofilm maturation pathways extracellular matrix biogenesis is the least understood. We propose a model in which the hypoxic biofilm environment is sensed by regulators such as Ccr4 to orchestrate metabolic adaptation, as well as the regulation of extracellular matrix production by impacting on the expression of matrix-related cell wall genes. Therefore metabolic changes in biofilms might be intimately linked to a key biofilm maturation mechanism that ultimately results in untreatable fungal disease.

  13. 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

  14. Deficient beta-mannosylation of Candida albicans phospholipomannan affects the proinflammatory response in macrophages.

    Directory of Open Access Journals (Sweden)

    Audrey Devillers

    Full Text Available Candida albicans produces a complex glycosphingolipid called phospholipomannan (PLM, which is present on the cell-wall surface of yeast and shed upon contact with host cells. The glycan moiety of PLM is composed of β-mannosides with degrees of polymerization up to 19 in C. albicans serotype A. PLM from serotype B strains displays a twofold decrease in the length of the glycan chains. In this study we compared the proinflammatory activities of PLMs purified from C. albicans serotype A and serotype B strains and from a bmt6Δ mutant of C. albicans, whose PLM is composed of short truncated oligomannosidic chain. We found that PLMs activate caspase-1 in murine macrophage cell line J774 independent of the glycan chain length although IL-1β secretion is more intense with long glycan chain. None of the tested PLMs stimulate ROS production, indicating that caspase-1 activation may occur through a ROS-independent pathway. On the other hand, only long-chain oligomannosides present on PLM from serotype A strain (PLM-A are able to induce TNF-α production in macrophages, a property that is not affect by blocking endocytosis through latrunculin A treatment. Finally, we demonstrate that soluble and not cell surface-bound galectin-3, is able to potentiate PLM-A-induced TNF-α production in macrophages. PLMs from C. albicans serotype B and from bmt6∆ mutant are not able to induce TNF-α production and galectin-3 pretreatment does not interfere with this result. In conclusion, we show here that PLMs are able to evoke a proinflammatory state in macrophage, which is in part dependent on their glycosylation status. Long-glycan chains favor interaction with soluble galectin-3 and help amplify inflammatory response.

  15. Deficient beta-mannosylation of Candida albicans phospholipomannan affects the proinflammatory response in macrophages.

    Science.gov (United States)

    Devillers, Audrey; Courjol, Flavie; Fradin, Chantal; Coste, Agnes; Poulain, Daniel; Pipy, Bernard; Bernardes, Emerson Soares; Jouault, Thierry

    2013-01-01

    Candida albicans produces a complex glycosphingolipid called phospholipomannan (PLM), which is present on the cell-wall surface of yeast and shed upon contact with host cells. The glycan moiety of PLM is composed of β-mannosides with degrees of polymerization up to 19 in C. albicans serotype A. PLM from serotype B strains displays a twofold decrease in the length of the glycan chains. In this study we compared the proinflammatory activities of PLMs purified from C. albicans serotype A and serotype B strains and from a bmt6Δ mutant of C. albicans, whose PLM is composed of short truncated oligomannosidic chain. We found that PLMs activate caspase-1 in murine macrophage cell line J774 independent of the glycan chain length although IL-1β secretion is more intense with long glycan chain. None of the tested PLMs stimulate ROS production, indicating that caspase-1 activation may occur through a ROS-independent pathway. On the other hand, only long-chain oligomannosides present on PLM from serotype A strain (PLM-A) are able to induce TNF-α production in macrophages, a property that is not affect by blocking endocytosis through latrunculin A treatment. Finally, we demonstrate that soluble and not cell surface-bound galectin-3, is able to potentiate PLM-A-induced TNF-α production in macrophages. PLMs from C. albicans serotype B and from bmt6∆ mutant are not able to induce TNF-α production and galectin-3 pretreatment does not interfere with this result. In conclusion, we show here that PLMs are able to evoke a proinflammatory state in macrophage, which is in part dependent on their glycosylation status. Long-glycan chains favor interaction with soluble galectin-3 and help amplify inflammatory response.

  16. The Role of Mms22p in DNA Damage Response in Candida albicans.

    Science.gov (United States)

    Yan, Lan; Xiong, Juan; Lu, Hui; Lv, Quan-zhen; Ma, Qian-yao; Côte, Pierre; Whiteway, Malcolm; Jiang, Yuan-ying

    2015-12-01

    To ensure correct DNA replication, eukaryotes have signaling pathways that respond to replication-associated DNA damage and trigger repair. In both Saccharomyces cerevisiae and Schizosaccharomyces pombe, a complex of proteins, including the cullin protein Rtt101p and two adapter proteins Mms22p and Mms1p, is important for proper response to replication stress. We have investigated this system in Candida albicans. In this pathogen, Mms22p is important for recovery from DNA replication damage induced by agents including methylmethane sulfonate, camptothecin, and ionizing radiation. Although no clear ortholog of Mms1p has been identified in C. albicans, loss of either Mms22p or Rtt101p generates similar damage sensitivity, consistent with a common function. In S. cerevisiae, the Mrc1p-Csm3p-Tof1p complex stabilizes stalled replication forks and activates a replication checkpoint and interacts with Mms22p. A similar complex in S. pombe, consisting of the Tof1p and Csm3p orthologs Swi1p and Swi3p, along with the fission yeast Mrc1p, genetically also interacts with Mms22p. Intriguingly in C. albicans only Mrc1p and Csm3p appear involved in damage repair, and Mms22p is required for responding to DNA damage agents in MRC1 or CSM3 conditional mutants. In C. albicans, although the loss of RAD57 greatly impairs response in the pathogen to many DNA-damaging agents, lethality due to camptothecin damage requires concomitant loss of Rad57p and Mms22p, suggesting that Mms22p is only essential for homologous recombination induced by camptothecin. These results establish that although C. albicans uses conserved cellular modules to respond to DNA damage and replication blocks, the specific details of these modules differ significantly from the S. cerevisiae model.

  17. 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.

  18. [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.

  19. Niche-specific requirement for hyphal wall protein 1 in virulence of Candida albicans.

    Directory of Open Access Journals (Sweden)

    Janet F Staab

    Full Text Available Specialized Candida albicans cell surface proteins called adhesins mediate binding of the fungus to host cells. The mammalian transglutaminase (TG substrate and adhesin, Hyphal wall protein 1 (Hwp1, is expressed on the hyphal form of C. albicans where it mediates fungal adhesion to epithelial cells. Hwp1 is also required for biofilm formation and mating thus the protein functions in both fungal-host and self-interactions. Hwp1 is required for full virulence of C. albicans in murine models of disseminated candidiasis and of esophageal candidiasis. Previous studies correlated TG activity on the surface of oral epithelial cells, produced by epithelial TG (TG1, with tight binding of C. albicans via Hwp1 to the host cell surfaces. However, the contribution of other Tgs, specifically tissue TG (TG2, to disseminated candidiasis mediated by Hwp1 was not known. A newly created hwp1 null strain in the wild type SC5314 background was as virulent as the parental strain in C57BL/6 mice, and virulence was retained in C57BL/6 mice deleted for Tgm2 (TG2. Further, the hwp1 null strains displayed modestly reduced virulence in BALB/c mice as did strain DD27-U1, an independently created hwp1Δ/Δ in CAI4 corrected for its ura3Δ defect at the URA3 locus. Hwp1 was still needed to produce wild type biofilms, and persist on murine tongues in an oral model of oropharyngeal candidiasis consistent with previous studies by us and others. Finally, lack of Hwp1 affected the translocation of C. albicans from the mouse intestine into the bloodstream of mice. Together, Hwp1 appears to have a minor role in disseminated candidiasis, independent of tissue TG, but a key function in host- and self-association to the surface of oral mucosa.

  20. 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

  1. Soft X-ray tomography of phenotypic switching and the cellular response to antifungal peptoids in Candida albicans

    OpenAIRE

    Uchida, Maho; McDermott, Gerry; Wetzler, Modi; Le Gros, Mark A.; Myllys, Markko; Knoechel, Christian; Barron, Annelise E.; Larabell, Carolyn A.

    2009-01-01

    The opportunistic pathogen Candida albicans can undergo phenotypic switching between a benign, unicellular phenotype and an invasive, multicellular form that causes candidiasis. Increasingly, strains of Candida are becoming resistant to antifungal drugs, making the treatment of candidiasis difficult, especially in immunocompromised or critically ill patients. Consequently, there is a pressing need to develop new drugs that circumvent fungal drug-resistance mechanisms. In this work we used sof...

  2. High throughput multiplex-PCR for direct detection and diagnosis of dermatophyte species, Candida albicans and Candida parapsilosis in clinical specimen.

    Science.gov (United States)

    Vahidnia, Ali; Bekers, Wouter; Bliekendaal, Harry; Spaargaren, Joke

    2015-06-01

    We have developed and validated a multiplex-PCR method for detection of dermatophyte spp., Candida albicans and parapsilosis for routine diagnostics. Our m-PCR showed excellent concordance with culture results in 475 clinical samples. Through the rapid diagnosis by our m-PCR, clinicians are able to initiate adequate antimycotic therapy much earlier.

  3. Distinct stages during colonization of the mouse gastrointestinal tract by Candida albicans

    Directory of Open Access Journals (Sweden)

    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.

  4. Release of lysosomal enzymes in Candida albicans phagocytosis by rat peritoneal macrophages.

    Science.gov (United States)

    Fontenla de Petrino, S E; Sirena, A

    1984-02-15

    The present paper reports the in vitro release of lysosomal enzymes in the supernatant of cultures of rat peritoneal macrophages, with the addition of Candida albicans cells. Macrophages were taken from the rat peritoneal cavity 72 hr after non-specific activation with Brain-Heart-Infusion (B.H.I.) broth containing 10% proteose-peptone No. 3. They were then cultured in Parker medium No. 199 (TC 199). After 24 hr a suspension of Candida albicans cells, in a determined concentration, was added to the peritoneal macrophage cultures. At that time, and during pre-determined periods, the following enzymes in the culture supernatants were studied using colorimetric methods: beta-glucuronidase, beta-galactosidase and acid phosphatase. It is concluded that, under identical conditions, the release of beta-galactosidase and acid phosphatase is higher than for beta-glucuronidase. The release rate of all three enzymes is the highest at a 6 hr incubation period, after which, a gradual decrease leads to the rate down to 50% at 24 hr.

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

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

    1989-05-01

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

  6. Antifungal activities of Terminalia ivorensis A. Chev. bark extracts against Candida albicans and Aspergillus fumigatus.

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    Ouattara Sitapha

    2013-02-01

    The present study was undertaken to evaluate in vitro antifungal activity of aqueous and hydroacoholic extracts from bark of Terminalia ivorensis A. Chev. (Combretaceae. In vitro antifungal activity of all the extracts was done by agar slant double dilution method. Candida albicans and Aspergillus fumigatus clinically important strains were used for the study. ketoconazole was used as standards for antifungal assay. Antifungal activity was determinated by evaluating of antifungal parameters values which are MCF (minimal concentration fungicide and IC50 (Concentration for 50% of inhibition around each assay. Result showed that the antifungal activity was more pronounced against Aspergillus fumigatus than Candida albicans. The hydroalcoholic extract showed best antifungal activity than ketoconazole. Demonstration of antifungal activity of T. ivorensis provides the scientific basis for the use of this plant in the traditional treatment of diseases and may help to discover new chemical classes of antifungal substances that could serve as selective agents for infectious disease chemotherapy. Keywords: Terminalia ivorensis, antifungal activity, clinical strains, hydroalcoholic extract [J Intercult Ethnopharmacol 2013; 2(1.000: 49-52

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

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    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.

  8. 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.

  9. PCR melting profile (PCR MP - a new tool for differentiation of Candida albicans strains

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    Nowak Magdalena

    2009-11-01

    Full Text Available Abstract Background We have previously reported the use of PCR Melting Profile (PCR MP technique based on using low denaturation temperatures during ligation mediated PCR (LM PCR for bacterial strain differentiation. The aim of the current study was to evaluate this method for intra-species differentiation of Candida albicans strains. Methods In total 123 Candida albicans strains (including 7 reference, 11 clinical unrelated, and 105 isolates from patients of two hospitals in Poland were examined using three genotyping methods: PCR MP, macrorestriction analysis of the chromosomal DNA by pulsed-field gel electrophoresis (REA-PFGE and RAPD techniques. Results The genotyping results of the PCR MP were compared with results from REA-PFGE and RAPD techniques giving 27, 26 and 25 unique types, respectively. The results showed that the PCR MP technique has at least the same discriminatory power as REA-PFGE and RAPD. Conclusion Data presented here show for the first time the evaluation of PCR MP technique for candidial strains differentiation and we propose that this can be used as a relatively simple and cheap technique for epidemiological studies in short period of time in hospital.

  10. Action of Coriandrum sativum L. Essential Oil upon Oral Candida albicans Biofilm Formation

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    V. F. Furletti

    2011-01-01

    Full Text Available The efficacy of extracts and essential oils from Allium tuberosum, Coriandrum sativum, Cymbopogon martini, Cymbopogon winterianus, and Santolina chamaecyparissus was evaluated against Candida spp. isolates from the oral cavity of patients with periodontal disease. The most active oil was fractionated and tested against C. albicans biofilm formation. The oils were obtained by water-distillation and the extracts were prepared with macerated dried plant material. The Minimal Inhibitory Concentration—MIC was determined by the microdilution method. Chemical characterization of oil constituents was performed using Gas Chromatography and Mass Spectrometry (GC-MS. C. sativum activity oil upon cell and biofilm morphology was evaluated by Scanning Electron Microscopy (SEM. The best activities against planktonic Candida spp. were observed for the essential oil and the grouped F8–10 fractions from C. sativum. The crude oil also affected the biofilm formation in C. albicans causing a decrease in the biofilm growth. Chemical analysis of the F8–10 fractions detected as major active compounds, 2-hexen-1-ol, 3-hexen-1-ol and cyclodecane. Standards of these compounds tested grouped provided a stronger activity than the oil suggesting a synergistic action from the major oil constituents. The activity of C. sativum oil demonstrates its potential for a new natural antifungal formulation.

  11. Influence of substratum position and acquired pellicle on Candida albicans biofilm

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    Indira Moraes Gomes Cavalcanti

    2013-11-01

    Full Text Available The purpose of this study was to evaluate the influence of the substratum position and the saliva acquired pellicle (AP on Candida albicans biofilm development. Poly(methylmethacrylate (PMMA disks were fabricated and randomly allocated to experimental groups: HNP (disks placed in a horizontal position and uncoated by pellicle, VNP (disks placed in a vertical position and uncoated by pellicle, HCP (disks placed in a horizontal position and coated by pellicle, and VCP (disks placed in a vertical position and coated by pellicle. Disks were placed in a 24-well plate and a suspension of 107 cells/mL of Candida albicans was added to each well for biofilm development. The plates were aerobically incubated at 35°C. The biofilms were evaluated at 1.5 (adhesion time point, 24, 48, 72, and 96 hours. The number of viable cells was quantified in terms of the colony-forming units per milliliter (CFU/mL. Metabolic activity was measured by the XTT assay. The biofilm structure was analyzed by scanning electron microscopy. The data were analyzed by three-way ANOVA followed by Tukey's test, with significance set at 5%. The vertical groups showed less biofilm formation and lower metabolic activity than the horizontal groups (ppp > 0.05. It can be concluded that the substratum position influenced biofilm development.

  12. Role of SFP1 in the Regulation of Candida albicans Biofilm Formation.

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    Hsueh-Fen Chen

    Full Text Available Candida albicans is a major human fungal pathogen. One of the important features of C. albicans pathogenicity is the ability to form biofilms on mucosal surfaces and indwelling medical devices. Biofilm formation involves complex processes in C. albicans, including cell adhesion, filamentous growth, extracellular matrix secretion and cell dispersion. In this work, we characterized the role of the transcription factor Sfp1, particularly with respect to its function in the regulation of biofilm formation. The deletion of the SFP1 gene enhanced cell adhesion and biofilm formation in comparison to the wild-type strain. Interestingly, the sfp1-deleted mutant also exhibited an increase in the expression of the ALS1, ALS3 and HWP1 genes, which encode adhesin proteins. In addition, Sfp1 was demonstrated to function downstream of the Rhb1-TOR signaling pathway. Bcr1 and Efg1 are transcription factors that are critical for controlling biofilm formation, and Efg1 is also required for hyphal growth. Deleting either the BCR1 or EFG1 gene in the sfp1-null background led to reduced adhesin gene expression. As a result, the bcr1/sfp1 or efg1/sfp1 double deletion mutants exhibited dramatically reduced biofilm formation. The results indicated that Sfp1 negatively regulates the ALS1, ALS3 and HWP1 adhesin genes and that the repression of these genes is mediated by the inhibition of Bcr1 and Efg1.

  13. 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.

  14. Synergistic Interactions of Eugenol-tosylate and Its Congeners with Fluconazole against Candida albicans.

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    Ahmad, Aijaz; Wani, Mohmmad Younus; Khan, Amber; Manzoor, Nikhat; Molepo, Julitha

    2015-01-01

    We previously reported the antifungal properties of a monoterpene phenol "Eugenol" against different Candida strains and have observed that the addition of methyl group to eugenol drastically increased its antimicrobial potency. Based on the results and the importance of medicinal synthetic chemistry, we synthesized eugenol-tosylate and its congeners (E1-E6) and tested their antifungal activity against different clinical fluconazole (FLC)- susceptible and FLC- resistant C. albicans isolates alone and in combination with FLC by determining fractional inhibitory concentration indices (FICIs) and isobolograms calculated from microdilution assays. Minimum inhibitory concentration (MIC) results confirmed that all the tested C. albicans strains were variably susceptible to the semi-synthetic derivatives E1-E6, with MIC values ranging from 1-62 μg/ml. The test compounds in combination with FLC exhibited either synergy (36%), additive (41%) or indifferent (23%) interactions, however, no antagonistic interactions were observed. The MICs of FLC decreased 2-9 fold when used in combination with the test compounds. Like their precursor eugenol, all the derivatives showed significant impairment of ergosterol biosynthesis in all C. albicans strains coupled with down regulation of the important ergosterol biosynthesis pathway gene-ERG11. The results were further validated by docking studies, which revealed that the inhibitors snugly fitting the active site of the target enzyme, mimicking fluconazole, may well explain their excellent inhibitory activity. Our results suggest that these compounds have a great potential as antifungals, which can be used as chemosensitizing agents with the known antifungal drugs.

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

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    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.

  16. 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.

  17. 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.

  18. Ribosomal protein S6 phosphorylation is controlled by TOR and modulated by PKA in Candida albicans.

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    Chowdhury, Tahmeena; Köhler, Julia R

    2015-10-01

    TOR and PKA signaling pathways control eukaryotic cell growth and proliferation. TOR activity in model fungi, such as Saccharomyces cerevisiae, responds principally to nutrients, e.g., nitrogen and phosphate sources, which are incorporated into the growing cell mass; PKA signaling responds to the availability of the cells' major energy source, glucose. In the fungal commensal and pathogen, Candida albicans, little is known of how these pathways interact. Here, the signal from phosphorylated ribosomal protein S6 (P-S6) was defined as a surrogate marker for TOR-dependent anabolic activity in C. albicans. Nutritional, pharmacologic and genetic modulation of TOR activity elicited corresponding changes in P-S6 levels. The P-S6 signal corresponded to translational activity of a GFP reporter protein. Contributions of four PKA pathway components to anabolic activation were then examined. In high glucose concentrations, only Tpk2 was required to upregulate P-S6 to physiologic levels, whereas all four tested components were required to downregulate P-S6 in low glucose. TOR was epistatic to PKA components with respect to P-S6. In many host niches inhabited by C. albicans, glucose is scarce, with protein being available as a nitrogen source. We speculate that PKA may modulate TOR-dependent cell growth to a rate sustainable by available energy sources, when monomers of anabolic processes, such as amino acids, are abundant.

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

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    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

  20. 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

  1. 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.

  2. 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.

  3. Lycopene induces apoptosis in Candida albicans through reactive oxygen species production and mitochondrial dysfunction.

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    Choi, Hyemin; Lee, Dong Gun

    2015-08-01

    Lycopene, a well-known carotenoid pigment found in tomatoes, has shown various biological functions. In our previous report, we showed that lycopene induces two apoptotic hallmarks, plasma membrane depolarization and G2/M cell cycle arrest, in Candida albicans. In this study, we investigated the ability of lycopene to induce apoptosis, and the mechanism by which it regulates apoptosis. FITC-Annexin V staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analysis, and 4',6-diamidino-2-phenylindole (DAPI) assay showed that lycopene exerted its antifungal activity during the early and late stages of apoptosis in C. albicans. During apoptosis, intracellular reactive oxygen species (ROS) were increased, and specifically the hydroxyl radicals contributed to the fungal cell death. Furthermore, lycopene treatment caused intracellular Ca(2+) overload and mitochondrial dysfunction, such as mitochondrial depolarization and cytochrome c release from the mitochondria to the cytoplasm. At last caspase activation was triggered. In summary, lycopene exerted its antifungal effects against C. albicans by inducing apoptosis via ROS production and mitochondrial dysfunction.

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

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    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

  5. 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.

  6. 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.

  7. 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.

  8. Levorotatory carbohydrates and xylitol subdue Streptococcus mutans and Candida albicans adhesion and biofilm formation.

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    Brambilla, Eugenio; Ionescu, Andrei C; Cazzaniga, Gloria; Ottobelli, Marco; Samaranayake, Lakshman P

    2016-05-01

    Dietary carbohydrates and polyols affect the microbial colonization of oral surfaces by modulating adhesion and biofilm formation. The aim of this study was to evaluate the influence of a select group of l-carbohydrates and polyols on either Streptococcus mutans or Candida albicans adhesion and biofilm formation in vitro. S. mutans or C. albicans suspensions were inoculated on polystyrene substrata in the presence of Tryptic soy broth containing 5% of the following compounds: d-glucose, d-mannose, l-glucose, l-mannose, d- and l-glucose (raceme), d- and l-mannose (raceme), l-glucose and l-mannose, sorbitol, mannitol, and xylitol. Microbial adhesion (2 h) and biofilm formation (24 h) were evaluated using MTT-test and Scanning Electron Microscopy (SEM). Xylitol and l-carbohydrates induced the lowest adhesion and biofilm formation in both the tested species, while sorbitol and mannitol did not promote C. albicans biofilm formation. Higher adhesion and biofilm formation was noted in both organisms in the presence of d-carbohydrates relative to their l-carbohydrate counterparts. These results elucidate, hitherto undescribed, interactions of the individually tested strains with l- and d-carbohydrates, and how they impact fungal and bacterial colonization. In translational terms, our data raise the possibility of using l-form of carbohydrates and xylitol for dietary control of oral plaque biofilms. PMID:26456320

  9. Efficacy of zosteric acid sodium salt on the yeast biofilm model Candida albicans.

    Science.gov (United States)

    Villa, Federica; Pitts, Betsey; Stewart, Philip S; Giussani, Barbara; Roncoroni, Simone; Albanese, Domenico; Giordano, Carmen; Tunesi, Marta; Cappitelli, Francesca

    2011-10-01

    Candida albicans is the most notorious and the most widely studied yeast biofilm former. Design of experiments (DoE) showed that 10 mg/L zosteric acid sodium salt reduced C. albicans adhesion and the subsequent biofilm formation by at least 70%, on both hydrophilic and hydrophobic surfaces of 96-well plates. Indeed, biofilm imaging revealed the dramatic impact of zosteric acid sodium salt on biofilm thickness and morphology, due to the inability of the cells to form filamentous structures while remaining metabolically active. In the same way, 10 mg/L zosteric acid sodium salt inhibited C. albicans biofilm formation when added after the adhesion phase. Contrary to zosteric acid sodium salt, methyl zosterate did not affect yeast biofilm. In addition, zosteric acid sodium salt enhanced sensitivity to chlorhexidine, chlorine, hydrogen peroxide, and cis-2-decenoic acid, with a reduction of 0.5 to 8 log units. Preliminary in vitro studies using suitable primary cell based models revealed that zosteric acid sodium salt did not compromise the cellular activity, adhesion, proliferation or morphology of either the murine fibroblast line L929 or the human osteosarcoma line MG-63. Thus the use of zosteric acid sodium salt could provide a suitable, innovative, preventive, and integrative approach to preventing yeast biofilm formation. PMID:21614460

  10. Levorotatory carbohydrates and xylitol subdue Streptococcus mutans and Candida albicans adhesion and biofilm formation.

    Science.gov (United States)

    Brambilla, Eugenio; Ionescu, Andrei C; Cazzaniga, Gloria; Ottobelli, Marco; Samaranayake, Lakshman P

    2016-05-01

    Dietary carbohydrates and polyols affect the microbial colonization of oral surfaces by modulating adhesion and biofilm formation. The aim of this study was to evaluate the influence of a select group of l-carbohydrates and polyols on either Streptococcus mutans or Candida albicans adhesion and biofilm formation in vitro. S. mutans or C. albicans suspensions were inoculated on polystyrene substrata in the presence of Tryptic soy broth containing 5% of the following compounds: d-glucose, d-mannose, l-glucose, l-mannose, d- and l-glucose (raceme), d- and l-mannose (raceme), l-glucose and l-mannose, sorbitol, mannitol, and xylitol. Microbial adhesion (2 h) and biofilm formation (24 h) were evaluated using MTT-test and Scanning Electron Microscopy (SEM). Xylitol and l-carbohydrates induced the lowest adhesion and biofilm formation in both the tested species, while sorbitol and mannitol did not promote C. albicans biofilm formation. Higher adhesion and biofilm formation was noted in both organisms in the presence of d-carbohydrates relative to their l-carbohydrate counterparts. These results elucidate, hitherto undescribed, interactions of the individually tested strains with l- and d-carbohydrates, and how they impact fungal and bacterial colonization. In translational terms, our data raise the possibility of using l-form of carbohydrates and xylitol for dietary control of oral plaque biofilms.

  11. 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.

  12. 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.

  13. Immunotherapy with intralesional Candida albicans antigen in resistant or recurrent warts: A study

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    Imran Majid

    2013-01-01

    Full Text Available Background: Warts are sometimes resistant or they tend to recur after every possible destructive therapy. Immunotherapy with skin-test antigens has been used as a viable therapeutic option in such recalcitrant cases. Aim: The aim of the study was to evaluate the response of resistant or recurrent warts to intralesional Candida albicans antigen immunotherapy. Materials and Methods: A total of 40 patients with resistant or recurrent warts who showed a positive test reaction to C. albicans antigen were given intralesional injections of purified C. albicans antigen solution in a single wart at 3-weekly intervals for a total of three doses. The patients were monitored for resolution of the injected wart as well as other untreated warts. The patients who responded positively were then followed up for any relapses over the next 6 months. Adverse events, if any, were also documented. Results: Of the 40 patients enrolled in the study, 34 completed the total treatment protocol of three injections and 6 months of follow-up. In these 34 patients, 19 (56% showed a complete resolution of warts at all places on the body. In addition, two patients (6% showed a partial or complete resolution of the treated wart, but there was no effect on the untreated warts. Thirteenpatients (38% failed to show any response to the treatment regimen. In all patients showing resolution of all the warts, there were no relapses at any site over the next 6 months of follow-up. The most common adverse effect seen was pain during the intralesional injection. Conclusions: Intralesional Candida immunotherapy seems to be an effective treatment option in more than half of the patients who fail to show a positive response to destructive modes of treatment or in whom there are multiple recurrences. Limitations: The small sample size and lack of control group are the main limitations of the study.

  14. Adherence of Candida albicans in cobalto- chromium and titanium alloys, with different sandpapering

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    Sidnei MARCACCI

    2008-04-01

    Full Text Available Introduction: The capacity of Candida albicans adherence is one ofits main factors of virulence. Surfaces of different materials canpropitiate conditions for higher or lower adherence and greater virulence of the microorganisms. Objective: Evaluate the adherence of Candida albicans in cobalto-chromium and titanium alloys, with different sandpapering. Material and methods: Twenty-four cylindrical samples have been constructed, 12 of titanium and 12 of cobalt-chromium, divided in 4 groups of six. All have been polished in the habitual form by the same technician. Samples have been sandpapered at about high rotation for 15 seconds each sandpaper, on all its surface. A group of each metal was sandpapered only with sandpaper for metal number 80. The two other groups have been sandpapered in agreement with the sequence (decreasing granulation: 80, 150 and 220. Samples have been sterilized and located in plates of cells culture. In each well of the plate was added standardized amount of Sabouraud broth and suspension containing 106 cells per milliliter of C. albicans (ATCC 18804. After incubation, the number of adhered cells per mm2 was obtained by the method of sowing in plate of Petri. The obtained values have been tabulated and submitted to the tests of ANOVA and Tukey,with level of significance of 5%. Results: There was statistical difference for the granulation of sandpapers, what not occurred when considering metals.Conclusion: The bigger the final granulation of sandpaper, the greater the adherence and the type of metal did not influence in the result.

  15. Comparison of VITEK 2 YST Card and API 20C AUX system in identification of non- albicans Candida species

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    Süleyman Durmaz

    2012-03-01

    Full Text Available Objectives: In the present study, it was aimed to compare results obtained by using VITEK 2 YST Card (bioMérieux, France with those obtained by using API 20C AUX (bioMérieux, France for identification of non- albicans Candida species, which was isolated from various clinical samples, at level of species.Materials and methods: Forty-one non-albicans Candida isolates, which were isolated from 28 urine, 10 blood and 3 vaginal swab specimens, and found to be negative by germ tube test, were identified by using VITEK 2 YST Card (bioMérieux, France. In addition, microscopic morphology was assessed in corn-meal Tween 80 agar, while carbohydrate assimilation was assessed by using commercially available API 20C AUX kit (bioMérieux, France.Results: Thirty-four isolates (82.9% were identified as identical species by these 2 systems, while different results were obtained in 7 isolates (17.1%. 5 isolates, identified as Candida glabrata by API 20C AUX system, were identified as Candida tropicalis (n=2, Candida krusei, Candida lipolitica and Candida kefyr by VITEK 2 YST Card. One other isolate, identified as C.tropicalis, was identified as Candida parapsilosis; and additional one isolate, identified as C.parapsilosis, was identified as C.tropicalis.Conclusion: It was concluded that one should be cautious in the identification of C.glabrata, in particular, C.tropicalis and C.parapsilosis, although between VITEK 2 YST Card and API 20C AUX system results was found largely similarity in identification of non-albicans Candida spp.

  16. Endoftalmite por Candida albicans após transplante penetrante de córnea: relato de caso Candida albicans endophthalmitis following penetrating corneal graft: case report

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    Glaucio de Godoy

    2004-04-01

    Full Text Available Os autores relatam o caso de uma paciente submetida a transplante penetrante de córnea por ceratocone que evoluiu com resposta inflamatória exacerbada durante o período pós-operatório, suspeitando-se, inicialmente, de rejeição atípica e intensa ao botão doador. Houve períodos de melhora, seguidos por períodos de piora a cada tentativa de se reduzir o corticóide tópico. Iniciou-se terapia imunossupressora com ciclosporina via oral e altas doses de corticóide tópico, porém, a paciente desenvolveu endoftalmite por Candida albicans com acometimento do segmento anterior do olho e do corpo vítreo, mas sem surgimento de lesões coriorretinianas. Evoluiu de forma satisfatória após três injeções de anfotericina B 5µg intravítrea, cetoconazol 400 mg/dia via oral e clotrimazol tópico de 4/4 horas. Os autores discutem também as principais possibilidades de contaminação da paciente, sendo o quadro infeccioso provavelmente relacionado ao procedimento cirúrgico.The authors report a case of a patient submitted to penetrating corneal graft for keratoconus with an exaggerated inflammatory response during the postoperative period. The patient was suspected of having an atypical rejection to the donor button. There were periods of improvement, followed by periods of worsening of the inflammation at each attempt of reducing the topical corticosteroid. After initiating immunosuppressive therapy with cyclosporin and high doses of topical corticosteroid, the patient developed Candida albicans endophthalmitis affecting the anterior segment of the eye and the vitreous body, but sparing the chorioretina. The patient improved after three injections of 5 µg intravitreal amphotericin B, 400 mg oral ketoconazole daily and topical clotrimazole every four hours. The authors also discuss the main possibilities of contamination of the patient, the infectious picture probably being related to the surgical procedure.

  17. 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

  18. 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.

  19. 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

  20. 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.