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Sample records for candida albicans mutants

  1. 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. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. Ability of Candida albicans Mutants To Induce Staphylococcus aureus Vancomycin Resistance during Polymicrobial Biofilm Formation▿

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    Harriott, Melphine M.; Noverr, Mairi C.

    2010-01-01

    Candida albicans and Staphylococcus aureus form vigorous polymicrobial biofilms in serum, which may serve as the source of coinfection in patients. More importantly, S. aureus is highly resistant to vancomycin during polymicrobial biofilm formation, with no decreases in bacterial viability observed with up to 1,600 μg/ml drug. In these mixed-species biofilms, S. aureus preferentially associates with C. albicans hyphae, which express a variety of unique adhesins. We tested C. albicans mutants deficient in transcriptional regulators of morphogenesis (CPH1 and EFG1) and biofilm formation (BCR1) to investigate the role of hyphae in mediating polymicrobial biofilm formation. These mutants also have reduced expression of hypha-specific adhesins. The ability to form polymicrobial biofilms correlated with the ability to form hyphae in these mutants. However, only mutants that could adhere to the abiotic surface could induce S. aureus vancomycin resistance, regardless of the presence of hyphae. In examining factors that may mediate interspecies adhesion, we found that the C. albicans ALS family of adhesins (Als1 to Als7 and Als9) was not involved, and neither was the hypha-specific adhesin Hwp1. Therefore, polymicrobial biofilm formation and subsequent antibiotic resistance is a multifactorial process that may require a unique combination of fungal and/or bacterial adhesins. PMID:20566760

  3. Genetic interactions among homologous recombination mutants in Candida albicans.

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    Bellido, Alberto; Andaluz, Encarnación; Gómez-Raja, Jonathan; Álvarez-Barrientos, Alberto; Larriba, Germán

    2015-01-01

    rad52-ΔΔ and, to a lesser extent, rad51-ΔΔ deletants of Candidaalbicans displayed slow growth and aberrant filamentous morphology whereas rad59-ΔΔ mutants, both by growth rate and morphology resembled wild type. In this study, we have constructed pair-wise double deletants to analyze genetic interactions among these homologous recombination (HR) proteins that affect growth and morphology traits. When grown in liquid YPD medium, double mutant rad51-ΔΔ rad59-ΔΔ exhibited growth rates, cell and colony morphologies, and plating efficiencies that were not significantly different from those observed for rad51-ΔΔ. The same was true for rad52-ΔΔ rad59-ΔΔ compared to rad52-ΔΔ. Slow growth and decreased plating efficiency were caused, at least in part, by a decreased viability, as deduced from FUN1 staining. Flow cytometry and microscopic studies of filamentous mutant populations revealed major changes in cell ploidy, size and morphology, whereas DAPI staining identified complex nuclear rearrangements in yeast and filamentous cells. These phenotypes were not observed in the rad59-ΔΔ mutant populations. Our results show that abolishing Rad51 functions induces the appearance of a subpopulation of aberrant yeast and filamentous forms with increased cell size and ploidy. The size of this complex subpopulation was exacerbated in rad52-ΔΔ mutants. The combination of filamentous cell morphology and viability phenotypes was reflected on the colony morphology of the respective mutants. We conclude that the rad52 mutation is epistatic to rad51 for all the morphological traits analyzed. We discuss these results in the light of the several functions of these recombination genes. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Candida albicans or Candida dubliniensis?

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    Ells, Ruan; Kock, Johan L F; Pohl, Carolina H

    2011-01-01

    Candida albicans is increasing as an opportunistic pathogen causing candidemia and candidiasis worldwide. In addition, other non-albicans Candida species are now also associated with pertinent infections. These include the closely related C. dubliniensis, which shares many phenotypic similarities with C. albicans. These similarities pose problems in the identification of isolates and have previously led to misidentification of these species. As a result, several identification techniques based on phenotypic and genotypic characteristics have been developed to differentiate between these Candida species. This review will focus on the similarities and differences between these two Candida species highlighting different identification methods and their advantages and disadvantages. © 2009 Blackwell Verlag GmbH.

  5. Microevolution of Candida albicans in macrophages restores filamentation in a nonfilamentous mutant.

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    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.

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

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    Amorim-Vaz, Sara; Delarze, Eric; Ischer, Françoise; Sanglard, Dominique; Coste, Alix T

    2015-01-01

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

  7. Analysis of the essentiality of ROM2 genes in the pathogenic yeasts Candida glabrata and Candida albicans using temperature-sensitive mutants.

    Science.gov (United States)

    Kanno, T; Takekawa, D; Miyakawa, Y

    2015-04-01

    To analyse the essentiality of the ROM2 genes originating from the pathogenic yeasts Candida glabrata and Candida albicans by using temperature-sensitive (ts) mutants. Based on the general concepts that ts mutations are generated by virtue of point mutation within essential genes, we have previously established a novel method (termed 'ETS system' for screening and identification of essential genes using ts mutants of C. glabrata). According to this ETS system, the present study successfully identified a putative C. glabrata ROM2 homologue as an essential gene that complements its point mutation (Cys-1275/Tyr substitution). The C. albicans ROM2 mutant (Cys-1281/Tyr), constructed patterned after this point mutation, also displayed ts phenotype. Both ts mutants recovered colony-forming ability, with concomitant suppression of lysis phenotype, at the elevated temperature in the presence of 1 mol l(-1) sorbitol as an osmotic stabilizer. Sequence alignment revealed that human genome possesses relatively low homology against Rom2 homologues, which are highly conserved among yeast species. ROM2 genes of C. glabrata and C. albicans are essential for viability, probably involved in cell wall integrity. ROM2 genes essential for both Candida species may be a potentially useful antifungal targets from chemotherapeutic viewpoint. © 2015 The Society for Applied Microbiology.

  8. Loss of Heterozygosity at an Unlinked Genomic Locus Is Responsible for the Phenotype of a Candida albicans sap4Δ sap5Δ sap6Δ Mutant

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    Dunkel, Nico; Morschhäuser, Joachim

    2011-01-01

    The diploid genome of the pathogenic yeast Candida albicans exhibits a high degree of heterozygosity. Genomic alterations that result in a loss of heterozygosity at specific loci may affect phenotypes and confer a selective advantage under certain conditions. Such genomic rearrangements can also occur during the construction of C. albicans mutants and remain undetected. The SAP2 gene on chromosome R encodes a secreted aspartic protease that is induced and required for growth of C. albicans wh...

  9. Analysis of Candida albicans mutants defective in the Cdk8 module of mediator reveal links between metabolism and biofilm formation.

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    Allia K Lindsay

    2014-10-01

    Full Text Available Candida albicans biofilm formation is a key virulence trait that involves hyphal growth and adhesin expression. Pyocyanin (PYO, a phenazine secreted by Pseudomonas aeruginosa, inhibits both C. albicans biofilm formation and development of wrinkled colonies. Using a genetic screen, we identified two mutants, ssn3Δ/Δ and ssn8Δ/Δ, which continued to wrinkle in the presence of PYO. Ssn8 is a cyclin-like protein and Ssn3 is similar to cyclin-dependent kinases; both proteins are part of the heterotetrameric Cdk8 module that forms a complex with the transcriptional co-regulator, Mediator. Ssn3 kinase activity was also required for PYO sensitivity as a kinase dead mutant maintained a wrinkled colony morphology in the presence of PYO. Furthermore, similar phenotypes were observed in mutants lacking the other two components of the Cdk8 module-Srb8 and Srb9. Through metabolomics analyses and biochemical assays, we showed that a compromised Cdk8 module led to increases in glucose consumption, glycolysis-related transcripts, oxidative metabolism and ATP levels even in the presence of PYO. In the mutant, inhibition of respiration to levels comparable to the PYO-treated wild type inhibited wrinkled colony development. Several lines of evidence suggest that PYO does not act through Cdk8. Lastly, the ssn3 mutant was a hyperbiofilm former, and maintained higher biofilm formation in the presence of PYO than the wild type. Together these data provide novel insights into the role of the Cdk8 module of Mediator in regulation of C. albicans physiology and the links between respiratory activity and both wrinkled colony and biofilm development.

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

    Directory of Open Access Journals (Sweden)

    Sara eAmorim-Vaz

    2015-05-01

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

  11. Kinetic analysis of site-directed mutants of methionine synthase from Candida albicans

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    Prasannan, Priya; Suliman, Huda S. [Institute of Cellular and Molecular Biology, Department of Chemistry and Biochemistry, 1 University Station A5300, University of Texas, Austin, TX 78712 (United States); Robertus, Jon D., E-mail: jrobertus@mail.utexas.edu [Institute of Cellular and Molecular Biology, Department of Chemistry and Biochemistry, 1 University Station A5300, University of Texas, Austin, TX 78712 (United States)

    2009-05-15

    Fungal methionine synthase catalyzes the transfer of a methyl group from 5-methyl-tetrahydrofolate to homocysteine to create methionine. The enzyme, called Met6p in fungi, is required for the growth of the pathogen Candida albicans, and is consequently a reasonable target for antifungal drug design. In order to understand the mechanism of this class of enzyme, we created a three-dimensional model of the C. albicans enzyme based on the known structure of the homologous enzyme from Arabidopsis thaliana. A fusion protein was created and shown to have enzyme activity similar to the wild-type Met6p. Fusion proteins containing mutations at eight key sites were expressed and assayed in this background. The D614 carboxylate appears to ion pair with the amino group of homocysteine and is essential for activity. Similarly, D504 appears to bind to the polar edge of the folate and is also required for activity. Other groups tested have lesser roles in substrate binding and catalysis.

  12. Candida albicans pathogenicity mechanisms.

    Science.gov (United States)

    Mayer, François L; Wilson, Duncan; Hube, Bernhard

    2013-02-15

    The polymorphic fungus Candida albicans is a member of the normal human microbiome. In most individuals, C. albicans resides as a lifelong, harmless commensal. Under certain circumstances, however, C. albicans can cause infections that range from superficial infections of the skin to life-threatening systemic infections. Several factors and activities have been identified which contribute to the pathogenic potential of this fungus. Among them are molecules which mediate adhesion to and invasion into host cells, the secretion of hydrolases, the yeast-to-hypha transition, contact sensing and thigmotropism, biofilm formation, phenotypic switching and a range of fitness attributes. Our understanding of when and how these mechanisms and factors contribute to infection has significantly increased during the last years. In addition, novel virulence mechanisms have recently been discovered. In this review we present an update on our current understanding of the pathogenicity mechanisms of this important human pathogen.

  13. Candida albicans pathogenicity mechanisms

    Science.gov (United States)

    Mayer, François L.; Wilson, Duncan; Hube, Bernhard

    2013-01-01

    The polymorphic fungus Candida albicans is a member of the normal human microbiome. In most individuals, C. albicans resides as a lifelong, harmless commensal. Under certain circumstances, however, C. albicans can cause infections that range from superficial infections of the skin to life-threatening systemic infections. Several factors and activities have been identified which contribute to the pathogenic potential of this fungus. Among them are molecules which mediate adhesion to and invasion into host cells, the secretion of hydrolases, the yeast-to-hypha transition, contact sensing and thigmotropism, biofilm formation, phenotypic switching and a range of fitness attributes. Our understanding of when and how these mechanisms and factors contribute to infection has significantly increased during the last years. In addition, novel virulence mechanisms have recently been discovered. In this review we present an update on our current understanding of the pathogenicity mechanisms of this important human pathogen. PMID:23302789

  14. Overexpression of YPT6 restores invasive filamentous growth and secretory vesicle clustering in a Candida albicans arl1 mutant.

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    Wakade, Rohan; Labbaoui, Hayet; Stalder, Danièle; Arkowitz, Robert A; Bassilana, Martine

    2017-09-29

    Virulence of the human fungal pathogen Candida albicans depends on the switch from budding to filamentous growth. Deletion of the Arf GTPase Arl1 results in hyphae that are shorter as well as reduced virulence. How Arl1 is regulated during hyphal growth, a process characteristic of filamentous fungi, yet absent in S. cerevisiae, is unknown. Here, we investigated the importance of the Rab6 homolog, Ypt6, in Arl1-dependent hyphal growth and determined that YPT6 overexpression specifically rescued the hyphal growth defect of an arl1 mutant, but not the converse. Furthermore, we show that deletion of ARL1 results in an alteration of the distribution of the Rab8 homolog, Sec4, in hyphal cells and that this defect is restored upon YPT6 overexpression.

  15. Innate immunity to Candida albicans

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    Yusuke Kiyoura

    2015-08-01

    Full Text Available Candida albicans is not a pathogen in healthy individuals, but can cause severe systemic candidiasis in immunocompromised patients. C. albicans has various virulence factors and activates the innate immune system. Specifically, C. albicans induces proinflammatory cytokine production in various cell types via many receptors, such as Toll-like receptors (TLRs and C-type lectin receptors (CLRs. This microorganism also promotes phagocytosis via CLRs on macrophages. In a previous study, we found that C. albicans induces the production of galectin-3, which is a known CLR that kills C. albicans. This review indicates that the use of mouthwash containing an antimicrobial peptide or protein might be a useful new oral care method for the prevention of oral candidiasis.

  16. β-(1,3)-Glucan Unmasking in Some Candida albicans Mutants Correlates with Increases in Cell Wall Surface Roughness and Decreases in Cell Wall Elasticity.

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    Hasim, Sahar; Allison, David P; Retterer, Scott T; Hopke, Alex; Wheeler, Robert T; Doktycz, Mitchel J; Reynolds, Todd B

    2017-01-01

    Candida albicans is among the most common human fungal pathogens, causing a broad range of infections, including life-threatening systemic infections. The cell wall of C. albicans is the interface between the fungus and the innate immune system. The cell wall is composed of an outer layer enriched in mannosylated glycoproteins (mannan) and an inner layer enriched in β-(1,3)-glucan and chitin. Detection of C. albicans by Dectin-1, a C-type signaling lectin specific for β-(1,3)-glucan, is important for the innate immune system to recognize systemic fungal infections. Increased exposure of β-(1,3)-glucan to the immune system occurs when the mannan layer is altered or removed in a process called unmasking. Nanoscale changes to the cell wall during unmasking were explored in live cells with atomic force microscopy (AFM). Two mutants, the cho1Δ/Δ and kre5Δ/Δ mutants, were selected as representatives that exhibit modest and strong unmasking, respectively. Comparisons of the cho1Δ/Δ and kre5Δ/Δ mutants to the wild type reveal morphological changes in their cell walls that correlate with decreases in cell wall elasticity. In addition, AFM tips functionalized with Dectin-1 revealed that the forces of binding of Dectin-1 to all of the strains were similar, but the frequency of binding was highest for the kre5Δ/Δ mutant, decreased for the cho1Δ/Δ mutant, and rare for the wild type. These data show that nanoscale changes in surface topology are correlated with increased Dectin-1 adhesion and decreased cell wall elasticity. AFM, using tips functionalized with immunologically relevant molecules, can map epitopes of the cell wall and increase our understanding of pathogen recognition by the immune system. Copyright © 2016 American Society for Microbiology.

  17. β-(1,3)-Glucan Unmasking in Some Candida albicans Mutants Correlates with Increases in Cell Wall Surface Roughness and Decreases in Cell Wall Elasticity

    Science.gov (United States)

    Hasim, Sahar; Allison, David P.; Retterer, Scott T.; Hopke, Alex; Wheeler, Robert T.; Doktycz, Mitchel J.

    2016-01-01

    ABSTRACT Candida albicans is among the most common human fungal pathogens, causing a broad range of infections, including life-threatening systemic infections. The cell wall of C. albicans is the interface between the fungus and the innate immune system. The cell wall is composed of an outer layer enriched in mannosylated glycoproteins (mannan) and an inner layer enriched in β-(1,3)-glucan and chitin. Detection of C. albicans by Dectin-1, a C-type signaling lectin specific for β-(1,3)-glucan, is important for the innate immune system to recognize systemic fungal infections. Increased exposure of β-(1,3)-glucan to the immune system occurs when the mannan layer is altered or removed in a process called unmasking. Nanoscale changes to the cell wall during unmasking were explored in live cells with atomic force microscopy (AFM). Two mutants, the cho1Δ/Δ and kre5Δ/Δ mutants, were selected as representatives that exhibit modest and strong unmasking, respectively. Comparisons of the cho1Δ/Δ and kre5Δ/Δ mutants to the wild type reveal morphological changes in their cell walls that correlate with decreases in cell wall elasticity. In addition, AFM tips functionalized with Dectin-1 revealed that the forces of binding of Dectin-1 to all of the strains were similar, but the frequency of binding was highest for the kre5Δ/Δ mutant, decreased for the cho1Δ/Δ mutant, and rare for the wild type. These data show that nanoscale changes in surface topology are correlated with increased Dectin-1 adhesion and decreased cell wall elasticity. AFM, using tips functionalized with immunologically relevant molecules, can map epitopes of the cell wall and increase our understanding of pathogen recognition by the immune system. PMID:27849179

  18. Budding off: bringing functional genomics to Candida albicans

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    Anderson, Matthew Z.

    2016-01-01

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

  19. Espondilodiscitis por Candida albicans Candida albicans spondylodiscitis: Diagnosis and Treatment

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    Silvina De Luca; Eduardo Mondello; Soledad Oviedo; Laura Tisser; Eduardo P. Eyheremendy; Carlos Rica

    2008-01-01

    Propósito: Describir los hallazgos radiológicos distintivos en resonancia magnética de las espondilodiscitis fúngicas (Candida albicans) y su importancia en el diagnóstico temprano de estas entidades. Se reporta el caso de un paciente masculino de 51 años de edad, inmunocomprometido, que consulta por fiebre y dolor lumbar. La RM con gadolinio demostró en secuencias T2 hipointensidad de la médula ósea en los cuerpos vertebrales afectados, asociados a cambios en la señal discal y realce intenso...

  20. Urinary tract infections and Candida albicans.

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    Behzadi, Payam; Behzadi, Elham; Ranjbar, Reza

    2015-01-01

    Urinary tract candidiasis is known as the most frequent nosocomial fungal infection worldwide. Candida albicans is the most common cause of nosocomial fungal urinary tract infections; however, a rapid change in the distribution of Candida species is undergoing. Simultaneously, the increase of urinary tract candidiasis has led to the appearance of antifungal resistant Candida species. In this review, we have an in depth look into Candida albicans uropathogenesis and distribution of the three most frequent Candida species contributing to urinary tract candidiasis in different countries around the world. For writing this review, Google Scholar -a scholarly search engine- (http://scholar.google.com/) and PubMed database (http://www.ncbi.nlm.nih.gov/pubmed/) were used. The most recently published original articles and reviews of literature relating to the first three Candida species causing urinary tract infections in different countries and the pathogenicity of Candida albicans were selected and studied. Although some studies show rapid changes in the uropathogenesis of Candida species causing urinary tract infections in some countries, Candida albicans is still the most important cause of candidal urinary tract infections. Despite the ranking of Candida albicans as the dominant species for urinary tract candidiasis, specific changes have occurred in some countries. At this time, it is important to continue the surveillance related to Candida species causing urinary tract infections to prevent, control and treat urinary tract candidiasis in future.

  1. Espondilodiscitis por Candida albicans Candida albicans spondylodiscitis: Diagnosis and Treatment

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    Silvina De Luca

    2008-03-01

    Full Text Available Propósito: Describir los hallazgos radiológicos distintivos en resonancia magnética de las espondilodiscitis fúngicas (Candida albicans y su importancia en el diagnóstico temprano de estas entidades. Se reporta el caso de un paciente masculino de 51 años de edad, inmunocomprometido, que consulta por fiebre y dolor lumbar. La RM con gadolinio demostró en secuencias T2 hipointensidad de la médula ósea en los cuerpos vertebrales afectados, asociados a cambios en la señal discal y realce intenso discovertebral. Ante un paciente inmunocomprometido con dolor lumbar que presenta modificaciones disco vertebrales atípicas en la resonancia magnética, debe considerarse la infección micótica dentro de las posibilidades diagnósticas. El diagnóstico de certeza requiere la toma de biopsia del tejido afectado mediante punción aspiración y posterior análisis microbiológico. El tratamiento médico es el de elección, aunque en algunos casos se plantea el drenaje quirúrgico. El reconocimiento de las características radiológicas distintivas evita retardos en el diagnóstico y el tratamiento.Purpose: To describe Candida albicans spondylodiscitis distinctive imaging findings and treatment. The authors reported a 51 years old, male inmunocompromised patient with fever and lumbar pain. MR findings include bone marrow hypointense signal intensity in T2 weighted of affected vertebral bodies and intense discovertebral enhancement. Candida albicans spondylodiscitis should be considered as one of the differential diagnosis of an inmunocompromised patient with lumbar pain and lumbar atypical findings at MR. Biopsy sample is required in order to reach final diagnosis. The first choice treatment is antyfungal drugs although in certain cases surgery is required. Rapid recognition of distinctive imaging findings avoid missdiagnosis and treatment delays.

  2. Null mutants of Candida albicans for cell-wall-related genes form fragile biofilms that display an almost identical extracellular matrix proteome.

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    Martínez, José P; Blanes, Rosario; Casanova, Manuel; Valentín, Eulogio; Murgui, Amelia; Domínguez, Ángel

    2016-11-01

    By two-dimensional gel electrophoresis (2-DE) and mass spectrometry, we have characterized the polypeptide species present in extracts obtained by 60% ethanol treatment of whole mature (48 h) biofilms formed by a reference strain (CAI4-URA3) and four Candida albicans null mutants for cell-wall-related genes (ALG5, CSA1, MNN9 and PGA10) Null mutants form fragile biofilms that appeared partially split and weakly attached to the substratum contrary to those produced by the reference strain. An almost identical, electrophoretic profile consisting of about 276 spots was visualized in all extracts examined. Proteomic analysis led to the identification of 131 polypeptides, corresponding to 86 different protein species, being the rest isoforms-83 displayed negative hydropathic indexes and 82 lack signal peptide. The majority of proteins appeared at pI between 4 and 6, and molecular mass between 10 and 94 kDa. The proteins identified belonged to the following Gene Ontology categories: 21.9% unknown molecular function, 16.2% oxidoreductase activity, 13.3% hydrolase activity and 41.8% distributed between other different GO categories. Strong defects in biofilm formation appreciated in the cell-wall mutant strains could be attributed to defects in aggregation due to abnormal cell wall formation rather than to differences in the biofilm extracellular matrix composition. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Triclosan antagonizes fluconazole activity against Candida albicans.

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    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.

  4. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Portrait of Candida albicans adherence regulators.

    Directory of Open Access Journals (Sweden)

    Jonathan S Finkel

    2012-02-01

    Full Text Available Cell-substrate adherence is a fundamental property of microorganisms that enables them to exist in biofilms. Our study focuses on adherence of the fungal pathogen Candida albicans to one substrate, silicone, that is relevant to device-associated infection. We conducted a mutant screen with a quantitative flow-cell assay to identify thirty transcription factors that are required for adherence. We then combined nanoString gene expression profiling with functional analysis to elucidate relationships among these transcription factors, with two major goals: to extend our understanding of transcription factors previously known to govern adherence or biofilm formation, and to gain insight into the many transcription factors we identified that were relatively uncharacterized, particularly in the context of adherence or cell surface biogenesis. With regard to the first goal, we have discovered a role for biofilm regulator Bcr1 in adherence, and found that biofilm regulator Ace2 is a major functional target of chromatin remodeling factor Snf5. In addition, Bcr1 and Ace2 share several target genes, pointing to a new connection between them. With regard to the second goal, our findings reveal existence of a large regulatory network that connects eleven adherence regulators, the zinc-response regulator Zap1, and approximately one quarter of the predicted cell surface protein genes in this organism. This limited yet sensitive glimpse of mutant gene expression changes had thus defined one of the broadest cell surface regulatory networks in C. albicans.

  6. Candida albicans escapes from mouse neutrophils

    DEFF Research Database (Denmark)

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

    2013-01-01

    Candida albicans, the most commonly isolated human fungal pathogen, is able to grow as budding yeasts or filamentous forms, such as hyphae. The ability to switch morphology has been attributed a crucial role for the pathogenesis of C. albicans. To mimic disseminated candidiasis in humans, the mouse...

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

    Science.gov (United States)

    Whibley, Natasha; Gaffen, Sarah L.

    2015-01-01

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

  8. Plasticity of Candida albicans Biofilms

    Science.gov (United States)

    Daniels, Karla J.

    2016-01-01

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

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

    Science.gov (United States)

    Martins, Carlos Henrique Gomes; Pires, Regina Helena; Cunha, Aline Oliveira; Pereira, Cristiane Aparecida Martins; Singulani, Junya de Lacorte; Abrão, Fariza; Moraes, Thais de; Mendes-Giannini, Maria José Soares

    2016-04-01

    Denture liners have physical properties that favour plaque accumulation and colonization by Candida species, irritating oral tissues and causing denture stomatitis. To isolate and determine the incidence of oral Candida species in dental prostheses, oral swabs were collected from the dental prostheses of 66 patients. All the strains were screened for their ability to form biofilms; both monospecies and dual-species combinations were tested. Candida albicans (63 %) was the most frequently isolated microorganism; Candida tropicalis (14 %), Candida glabrata (13 %), Candida rugosa (5 %), Candida parapsilosis (3 %), and Candida krusei (2 %) were also detected. The XTT assay showed that C. albicans SC5314 possessed a biofilm-forming ability significantly higher (p biofilm was less than the total CFU of a monospecies C. albicans biofilm. In contrast to the profuse hyphae verified in monospecies C. albicans biofilms, micrographies showed that the C. albicans/non-albicans Candida biofilms consisted of sparse yeast forms and profuse budding yeast cells that generated a network. These results suggested that C. albicans and the tested Candida species could co-exist in biofilms displaying apparent antagonism. The study provide the first description of C. albicans/C. rugosa mixed biofilm. Copyright © 2016 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

  10. Development of DNA probes for Candida albicans

    Energy Technology Data Exchange (ETDEWEB)

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

    1988-07-01

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

  11. Molecular genetic techniques for gene manipulation in Candida albicans

    Science.gov (United States)

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

    2014-01-01

    Candida albicans is one of the most common fungal pathogen in humans due to its high frequency as an opportunistic and pathogenic fungus causing superficial as well as invasive infections in immunocompromised patients. An understanding of gene function in C. albicans is necessary to study the molecular basis of its pathogenesis, virulence and drug resistance. Several manipulation techniques have been used for investigation of gene function in C. albicans, including gene disruption, controlled gene expression, protein tagging, gene reintegration, and overexpression. In this review, the main cassettes containing selectable markers used for gene manipulation in C. albicans are summarized; the advantages and limitations of these cassettes are discussed concerning the influences on the target gene expression and the virulence of the mutant strains. PMID:24759671

  12. Antibiotic resistance in Candida albicans and Staphylococcus ...

    African Journals Online (AJOL)

    Nowadays, vaginal candidiasis and bacterial vaginosis are frequently encountered in medical practice and antibiotic resistance in implicated pathogens has not been reported in Dschang. This study sought to determine the antimicrobial susceptibility patterns of 198 isolates of Candida albicans and 300 strains of ...

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

    Directory of Open Access Journals (Sweden)

    Katja Palige

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

  14. 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.

  15. 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. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  16. Candida albicans isolates from a Malaysian hospital exhibit more potent phospholipase and haemolysin activities than non-albicans Candida isolates.

    Science.gov (United States)

    Chin, V K; Foong, K J; Maha, A; Rusliza, B; Norhafizah, M; Ng, K P; Chong, P P

    2013-12-01

    This study was aimed at determining the phospholipase and haemolysin activity of Candida isolates in Malaysia. A total of 37 Candida clinical isolates representing seven species, Candida albicans (12), Candida tropicalis (8), Candida glabrata (4), Candida parapsilosis (1), Candida krusei (4), Candida orthopsilosis (1) and Candida rugosa (7) were tested. In vitro phospholipase activity was determined by using egg yolk plate assay whereas in vitro haemolysin activity was tested by using blood plate assay on sheep blood Sabouraud's dextrose agar (SDA) enriched with glucose. Phospholipase activity was detected in 75% (9 out of 12) of the C. albicans isolates. Among the 25 non- C. albicans Candida isolates, phospholipase activity was detected in only 24% of these isolates. The phospholipase activity of C. albicans was significantly higher than that of the non- C. albicans Candida isolates (P=0.002). Haemolysin activity was detected in 100% of the C. albicans, C. tropicalis, C. glabrata, C. krusei, C. parapsilosis, and C. orthopsilosis isolates while 75% of the C. krusei isolates and 12.3% of the C. rugosa isolates showed haemolysin activity. The haemolytic activity of C. albicans was significantly higher than that of the non- C. albicans Candida isolates (P=0.0001).The findings in this study indicate that C. albicans isolates in Malaysia may possess greater virulence potential than the non-albicans species.

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

    Science.gov (United States)

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

    2017-01-01

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

  18. Factors Supporting Cysteine Tolerance and Sulfite Production in Candida albicans

    Science.gov (United States)

    Hennicke, Florian; Grumbt, Maria; Lermann, Ulrich; Ueberschaar, Nico; Palige, Katja; Böttcher, Bettina; Jacobsen, Ilse D.; Staib, Claudia; Morschhäuser, Joachim; Monod, Michel; Hube, Bernhard; Hertweck, Christian

    2013-01-01

    The amino acid cysteine has long been known to be toxic at elevated levels for bacteria, fungi, and humans. However, mechanisms of cysteine tolerance in microbes remain largely obscure. Here we show that the human pathogenic yeast Candida albicans excretes sulfite when confronted with increasing cysteine concentrations. Mutant construction and phenotypic analysis revealed that sulfite formation from cysteine in C. albicans relies on cysteine dioxygenase Cdg1, an enzyme with similar functions in humans. Environmental cysteine induced not only the expression of the CDG1 gene in C. albicans, but also the expression of SSU1, encoding a putative sulfite efflux pump. Accordingly, the deletion of SSU1 resulted in enhanced sensitivity of the fungal cells to both cysteine and sulfite. To study the regulation of sulfite/cysteine tolerance in more detail, we screened a C. albicans library of transcription factor mutants in the presence of sulfite. This approach and subsequent independent mutant analysis identified the zinc cluster transcription factor Zcf2 to govern sulfite/cysteine tolerance, as well as cysteine-inducible SSU1 and CDG1 gene expression. cdg1Δ and ssu1Δ mutants displayed reduced hypha formation in the presence of cysteine, indicating a possible role of the newly proposed mechanisms of cysteine tolerance and sulfite secretion in the pathogenicity of C. albicans. Moreover, cdg1Δ mutants induced delayed mortality in a mouse model of disseminated infection. Since sulfite is toxic and a potent reducing agent, its production by C. albicans suggests diverse roles during host adaptation and pathogenicity. PMID:23417561

  19. Comparative antifungal susceptibility analysis of Candida albicans versus non-albicans Candida corneal isolates.

    Science.gov (United States)

    Spierer, Oriel; Dugar, Jyoti; Miller, Darlene; OʼBrien, Terrence P

    2015-05-01

    To compare the in vitro activity of topical amphotericin B (AMB), natamycin, voriconazole, and fluconazole against human corneal isolates of Candida sp. for guidance in the treatment of Candida keratitis. Sixty-eight Candida isolates (37 albicans and 31 non-albicans isolates) recovered from corneal scrapings submitted to rule out microbial keratitis, during the years 2005 to 2011, at the Bascom Palmer Eye Institute, were examined in this study. Corneal isolates were cultured on fungal agars for 48 hours. Each yeast isolate was dispensed into 4 microtiter wells, each containing 100 mL of commercial (natamycin 5%) or compounded (AMB 0.15%, voriconazole 1%, and fluconazole 0.2%) antifungal medications. A comparison of growth patterns was conducted. One hundred percent of the samples showed growth inhibition after treatment exposure with AMB or natamycin. The isolates treated with voriconazole demonstrated an 85% inhibition rate overall, with the Candida albicans samples showing a 77% inhibition rate and the non-albicans sp. a 93% inhibition rate. In the fluconazole group, there was only a 19.6% inhibition rate noted, with a 7.7% inhibition rate observed in the C. albicans group versus a 30% inhibition rate in the non-albicans group. AMB 0.2% and natamycin 5% have equal effectiveness and full inhibition against Candida keratitis isolates. Fluconazole 0.2% is not the drug of choice in both C. albicans and non-albicans keratitis. Voriconazole 1% may need a stronger concentration for higher effectiveness, but potentially may be helpful as a second agent in the treatment of Candida keratitis.

  20. Psd1 Effects on Candida albicans Planktonic Cells and Biofilms

    Directory of Open Access Journals (Sweden)

    Sónia Gonçalves

    2017-06-01

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

  1. Candida albicans Biofilms and Human Disease.

    Science.gov (United States)

    Nobile, Clarissa J; Johnson, Alexander D

    2015-01-01

    In humans, microbial cells (including bacteria, archaea, and fungi) greatly outnumber host cells. Candida albicans is the most prevalent fungal species of the human microbiota; this species asymptomatically colonizes many areas of the body, particularly the gastrointestinal and genitourinary tracts of healthy individuals. Alterations in host immunity, stress, resident microbiota, and other factors can lead to C. albicans overgrowth, causing a wide range of infections, from superficial mucosal to hematogenously disseminated candidiasis. To date, most studies of C. albicans have been carried out in suspension cultures; however, the medical impact of C. albicans (like that of many other microorganisms) depends on its ability to thrive as a biofilm, a closely packed community of cells. Biofilms are notorious for forming on implanted medical devices, including catheters, pacemakers, dentures, and prosthetic joints, which provide a surface and sanctuary for biofilm growth. C. albicans biofilms are intrinsically resistant to conventional antifungal therapeutics, the host immune system, and other environmental perturbations, making biofilm-based infections a significant clinical challenge. Here, we review our current knowledge of biofilms formed by C. albicans and closely related fungal species.

  2. Candida albicans Biofilms and Human Disease

    Science.gov (United States)

    Nobile, Clarissa J.; Johnson, Alexander D.

    2016-01-01

    In humans, microbial cells (including bacteria, archaea, and fungi) greatly outnumber host cells. Candida albicans is the most prevalent fungal species of the human microbiota; this species asymptomatically colonizes many areas of the body, particularly the gastrointestinal and genitourinary tracts of healthy individuals. Alterations in host immunity, stress, resident microbiota, and other factors can lead to C. albicans overgrowth, causing a wide range of infections, from superficial mucosal to hematogenously disseminated candidiasis. To date, most studies of C. albicans have been carried out in suspension cultures; however, the medical impact of C. albicans (like that of many other microorganisms) depends on its ability to thrive as a biofilm, a closely packed community of cells. Biofilms are notorious for forming on implanted medical devices, including catheters, pacemakers, dentures, and prosthetic joints, which provide a surface and sanctuary for biofilm growth. C. albicans biofilms are intrinsically resistant to conventional antifungal therapeutics, the host immune system, and other environmental perturbations, making biofilm-based infections a significant clinical challenge. Here, we review our current knowledge of biofilms formed by C. albicans and closely related fungal species. PMID:26488273

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

    Directory of Open Access Journals (Sweden)

    Apurva K Pathak

    2012-02-01

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

  4. Alteramide B is a microtubule antagonist of inhibiting Candida albicans.

    Science.gov (United States)

    Ding, Yanjiao; Li, Yaoyao; Li, Zhenyu; Zhang, Juanli; Lu, Chunhua; Wang, Haoxin; Shen, Yuemao; Du, Liangcheng

    2016-10-01

    Alteramide B (ATB), isolated from Lysobacter enzymogenes C3, was a new polycyclic tetramate macrolactam (PTM). ATB exhibited potent inhibitory activity against several yeasts, particularly Candida albicans SC5314, but its antifungal mechanism is unknown. The structure of ATB was established by extensive spectroscopic analyses, including high-resolution mass spectrometry, 1D- and 2D-NMR, and CD spectra. Flow cytometry, fluorescence microscope, transmission electron microscope, molecular modeling, overexpression and site-directed mutation studies were employed to delineate the anti-Candida molecular mechanism of ATB. ATB induced apoptosis in C. albicans through inducing reactive oxygen species (ROS) production by disrupting microtubules. Molecular dynamics studies revealed the binding patterns of ATB to the β-tubulin subunit. Overexpression of the wild type and site-directed mutants of the β-tubulin gene (TUBB) changed the sensitivity of C. albicans to ATB, confirming the binding of ATB to β-tubulin, and indicating that the binding sites are L215, L217, L273, L274 and R282. In vivo, ATB significantly improved the survival of the candidiasis mice and reduced fungal burden. The molecular mechanism underlying the ATB-induced apoptosis in C. albicans is through inhibiting tubulin polymerization that leads to cell cycle arrest at the G2/M phase. The identification of ATB and the study of its activity provide novel mechanistic insights into the mode of action of PTMs against the human pathogen. This study shows that ATB is a new microtubule inhibitor and a promising anti-Candida lead compound. The results also support β-tubulin as a potential target for anti-Candida drug discovery. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. An extensive circuitry for cell wall regulation in Candida albicans.

    Directory of Open Access Journals (Sweden)

    Jill R Blankenship

    2010-02-01

    Full Text Available Protein kinases play key roles in signaling and response to changes in the external environment. The ability of Candida albicans to quickly sense and respond to changes in its environment is key to its survival in the human host. Our guiding hypothesis was that creating and screening a set of protein kinase mutant strains would reveal signaling pathways that mediate stress response in C. albicans. A library of protein kinase mutant strains was created and screened for sensitivity to a variety of stresses. For the majority of stresses tested, stress response was largely conserved between C. albicans, Saccharomyces cerevisiae, and Schizosaccharomyces pombe. However, we identified eight protein kinases whose roles in cell wall regulation (CWR were not expected from functions of their orthologs in the model fungi Saccharomyces cerevisiae and Schizosaccharomyces pombe. Analysis of the conserved roles of these protein kinases indicates that establishment of cell polarity is critical for CWR. In addition, we found that septins, crucial to budding, are both important for surviving and are mislocalized by cell wall stress. Our study shows an expanded role for protein kinase signaling in C. albicans cell wall integrity. Our studies suggest that in some cases, this expansion represents a greater importance for certain pathways in cell wall biogenesis. In other cases, it appears that signaling pathways have been rewired for a cell wall integrity response.

  6. 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. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. Candida albicans adherence to glass ionomer restorative dental material

    Directory of Open Access Journals (Sweden)

    Shirin Lawaf

    2009-06-01

    Full Text Available Background and aims. It is believed that adherence of Candida albicans to oral surfaces is a critical event in the colonization and development of oral diseases such as candida-associated denture stomatitis. Although there is considerable information about the adherence of Candida albicans to buccal epithelial cells and prosthetic materials, there is very little information available about the adherence of Candida albicans to glass ionomer materials. The purpose of this study was to investigate the degree of Candida albicans adherence to glass ionomer restorative material. Materials and methods. In this experimental study adherence of Candida albicans strains was studied with and without human whole saliva. First, glass ionomer fragments were prepared; then yeast cells were inoculated and incubated with different incubation times. After incubation, the fragments were removed from the wells and stained with 0.1% calcofluor white. Adhesion was quantified by counting the total number of cells at 40, 80 and 120 minutes. The analysis of variance and Student's test were used to assess the significance of differences between the means. Results. In the absence of saliva, the adherence of Candida albicans showed an increase, reaching a maximum at the end of the experiment (120 minutes. However, in the presence of saliva, the adherence of Candida albicans to glass ionomer significantly decreased. Conclusion. The presence of human whole saliva is an important factor in the adherence of Candida albicans to glass ionomer restorative material.

  8. Comparison of the clinical risk factors between Candida albicans and Candida non-albicans species for bloodstream infection.

    Science.gov (United States)

    Shigemura, Katsumi; Osawa, Kayo; Jikimoto, Takumi; Yoshida, Hiroyuki; Hayama, Brian; Ohji, Goh; Iwata, Kentaro; Fujisawa, Masato; Arakawa, Soichi

    2014-04-01

    The purpose of this study is to investigate the risk factors and susceptibilities to antifungal agents of Candida albicans and Candida non-albicans species (spp.) in candidemia cases in Kobe University Hospital. We investigated all consecutive patients with candida bloodstream infection (BSI) from 2008-2013 for whose full data were available for analyses, examining clinical factors such as gender, general complications, postoperative status or susceptibilities to antifungal agents. These factors were also compared between Candida albicans spp. and Candida non-albicans by univariate and multivariate analyses. Univariate analyses showed a significantly higher rate of Candida non-albicans species BSI patients cancer (odds ratio (OR) (95% confidence interval (CI))=2.29 (1.04-5.06) and P=0.040), chemotherapy (OR=4.35 (1.11-17.1) and P=0.035), fluconazole (FLCZ) resistance (OR=77.3 (4.51-1324) and P=0.003), and itraconazole (ITCZ) resistance (OR=15.6 (5.39-45.1) and PCandida albicans. Multivariate analyses demonstrated that Candida non-albicans spp. had significantly higher rate of chemotherapy (OR=4.44 (1.04-19.0) and P=0.045), FLCZ resistance (OR=5.87 (2.01-17.1) and P=0.001), and ITCZ resistance (OR=18.7(5.77-60.4) and PCandida albicans. In conclusion, this study revealed several risk factors for BSI with Candida albicans (underlying cardiovascular diseases and postoperative status) and Candida non-albicans spp. (cancer and chemotherapy), and demonstrated that Candida non-albicans spp. were more resistant to FLCZ and ITCZ than Candida albicans.

  9. Frequency of Candida albicans in Patients with Funguria.

    Science.gov (United States)

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

    2016-02-01

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

  10. Enterococcus faecalis Inhibits Hyphal Morphogenesis and Virulence of Candida albicans

    Science.gov (United States)

    Cruz, Melissa R.; Graham, Carrie E.; Gagliano, Bryce C.

    2013-01-01

    The Gram-positive bacterium Enterococcus faecalis and the fungus Candida albicans are both found as commensals in many of the same niches of the human body, such as the oral cavity and gastrointestinal (GI) tract. However, both are opportunistic pathogens and have frequently been found to be coconstituents of polymicrobial infections. Despite these features in common, there has been little investigation into whether these microbes affect one another in a biologically significant manner. Using a Caenorhabditis elegans model of polymicrobial infection, we discovered that E. faecalis and C. albicans negatively impact each other's virulence. Much of the negative effect of E. faecalis on C. albicans was due to the inhibition of C. albicans hyphal morphogenesis, a developmental program crucial to C. albicans pathogenicity. We discovered that the inhibition was partially dependent on the Fsr quorum-sensing system, a major regulator of virulence in E. faecalis. Specifically, two proteases regulated by Fsr, GelE and SerE, were partially required. Further characterization of the inhibitory signal revealed that it is secreted into the supernatant, is heat resistant, and is between 3 and 10 kDa. The substance was also shown to inhibit C. albicans filamentation in the context of an in vitro biofilm. Finally, a screen of an E. faecalis transposon mutant library identified other genes required for suppression of C. albicans hyphal formation. Overall, we demonstrate a biologically relevant interaction between two clinically important microbes that could affect treatment strategies as well as impact our understanding of interkingdom signaling and sensing in the human-associated microbiome. PMID:23115035

  11. 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.

  12. Mucosal Immunity and Candida albicans Infection

    Directory of Open Access Journals (Sweden)

    David L. Moyes

    2011-01-01

    Full Text Available Interactions between mucosal surfaces and microbial microbiota are key to host defense, health, and disease. These surfaces are exposed to high numbers of microbes and must be capable of distinguishing between those that are beneficial or avirulent and those that will invade and cause disease. Our understanding of the mechanisms involved in these discriminatory processes has recently begun to expand as new studies bring to light the importance of epithelial cells and novel immune cell subsets such as Th17 T cells in these processes. Elucidating how these mechanisms function will improve our understanding of many diverse diseases and improve our ability to treat patients suffering from these conditions. In our voyage to discover these mechanisms, mucosal interactions with opportunistic commensal organisms such as the fungus Candida albicans provide insights that are invaluable. Here, we review current knowledge of the interactions between C. albicans and epithelial surfaces and how this may shape our understanding of microbial-mucosal interactions.

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

    African Journals Online (AJOL)

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

  14. Antifungal drug susceptibility of Candida albicans | Bii | East African ...

    African Journals Online (AJOL)

    Objective: To determine the susceptibility of clinical isolates of Candida albicans and to establish the minimum inhibitory concentrations (MIC) to commonly used antifungal drugs. Design: Laboratory based experiment. Setting: Mbagathi District Hospital, Nairobi, Kenya. Subjects: Candida albicans isolated between 1998 ...

  15. Otite externe maligne à Candida Albicans

    Science.gov (United States)

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

    2016-01-01

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

  16. Identification of Fibronectin Adhesins on Candida albicans

    OpenAIRE

    VARDAR-ÜNLÜ, Gülhan

    2014-01-01

    The pattern of distribution of fibronectin adhesins on yeast and hyphal-form Candida albicanswas studied with gold-labelled fibronectin and transmission electron microscopy. The germ-tube parts of the hyphal-form cells were the major binding sites for gold-labelled fibronectin, and the attached yeast-cell parts and yeast-form cell remained unlabelled. Therefore, the walls of the germ tube parts of hyphal-form cells might be sites of important interactions between C. albicans and ho...

  17. Mycosynthesis of Silver Nanoparticles from Candida albicans and its ...

    African Journals Online (AJOL)

    Purpose: To produce and characterize silver nanoparticles using Candida albicans and evaluate its antibacterial properties. Methods: Extracellular silver nanoparticles were biosynthesized using C. albicans. The biomass obtained from cultures of C. albicans was used to synthesize silver nanoparticles in 1.5 mM silver ...

  18. Candida albicans morphologies revealed by scanning electron microscopy analysis

    Directory of Open Access Journals (Sweden)

    M. Staniszewska

    2013-09-01

    Full Text Available Scanning electron microscope (SEM observations were used to analyze particular morphologies of Candida albicans clinical isolate (strain 82 and mutants defective in hyphae-promoting genes EFG1 (strain HLC52 and/ or CPH1 (strains HLC54 and Can16. Transcription factors Efg1 and Cph1 play role in regulating filamentation and adhesion of C. albicans' morphologies. Comparative analysis of such mutants and clinical isolate showed that Efg1 is required for human serum-induced cell growth and morphological switching. In the study, distinct differences between ultrastructural patterns of clinical strain's and null mutants' morphologies were observed (spherical vs tube-like blastoconidia, or solid and fragile constricted septa vs only the latter observed in strains with EFG1 deleted. In addition, wild type strain displayed smooth colonies of cells in comparison to mutants which exhibited wrinkled phenotype. It was observed that blastoconidia of clinical strain exhibited either polarly or randomly located budding. Contrariwise, morphotypes of mutants showed either multiple polar budding or a centrally located single bud scar (mother-daughter cell junction distinguishing tube-like yeast/ pseudohyphal growth (the length-to-width ratios larger than 1.5. In their planktonic form of growth, blastoconidia of clinical bloodstream isolate formed constitutively true hyphae under undiluted human serum inducing conditions. It was found that true hyphae are essential elements for developing structural integrity of conglomerate, as mutants displaying defects in their flocculation and conglomerate-forming abilities in serum. While filamentation is an important virulence trait in C. albicans the true hyphae are the morphologies which may be expected to play a role in bloodstream infections.

  19. [Candida: epidemiology and risk factors for non-albicans species].

    Science.gov (United States)

    Cornistein, Wanda; Mora, Andrea; Orellana, Nora; Capparelli, Federico Javier; del Castillo, Marcelo

    2013-01-01

    Nosocomial fungal infections have increased significantly in the last decade. Candida detection in clinical specimens can mean either colonization or an infection which can be local (muguet) or invasive. Knowledge of the species helps in choosing the best treatment. The aims of this study were to determine the frequency and distribution of Candida species detected in clinical samples, to analyze the clinical characteristics of the involved population and to determine the risk factors for Candida non-albicans species. Retrospective, observational. 2006-2010. all isolates of Candida in clinical specimens from patients hospitalized at least 48 hours in a neurological center. We analyzed epidemiological characteristics, co morbidities, risk factors, factors associated with Candida non-albicans detection, antifungal treatment, development of adverse events and mortality. Candida spp. was isolated from 321 clinical specimens: 139 (43.3%) were C. albicans and 182 (56.7%) Candida non-albicans. The distribution of the sample was: urine 122 (Candida non-albicans 67.2%), airway 81, oropharynx 45 (C. albicans) and candidemia 40 (Candida non-albicans 75%). The most frequent co-morbidity was solid tumor (35.5%). The main risk factors were antibiotic therapy (85.5%), steroid therapy (61.7%) and in ICU at diagnosis (61.6%). The analysis of risk factors and the isolation of Candida non-albicans shows that chemotherapy, previous surgery, treatment with aminopenicillins, carbapenems and glycopeptides were statistically significant (PCandida species distribution varies with the type of sample analyzed. Non-albicans species make up the majority of the isolates. The identification of the species involved per sample helps to optimize treatment. The high frequency of isolation of Candida in patients on steroids and antibiotics and admitted to ICU, is worth pointing out. Patients with previous surgery, treated with the aforementioned antibiotics or chemotherapy, could receive non

  20. Comparison of the MUREX C. albicans, Albicans-Sure, and BactiCard Candida test kits with the germ tube test for presumptive identification of Candida albicans.

    OpenAIRE

    Crist, A E; Dietz, T J; Kampschroer, K.

    1996-01-01

    The MUREX C. albicans (MC)(Murex Diagnostics), Albicans-Sure (AS) (Clinical Standards Laboratories), and BactiCard Candida (BC) (Remel) test kits were compared with the germ tube (GT) test for the rapid, presumptive identification of Candida albicans. All three test kits detect the enzymes L-proline aminopeptidase and beta-galactosaminidase in yeast cells grown on culture media and are based on the principle that C. albicans produces both enzymes whereas other yeasts produce only one or neith...

  1. Stability of Candida albicans allergens during storage.

    Science.gov (United States)

    Savolainen, J; Viander, M; Einarsson, R; Nieminen, E; Koivikko, A

    1992-11-01

    Stability of Candida albicans allergens was studied under various storage conditions. Lyophilized extract was reconstituted with human serum albumin (NSA) diluent, glycerol-free and in the presence of 10% or 50% glycerol and stored at various temperatures for different time periods. All extracts were tested at the same time with immunoblotting using C. albicans allergic patient sera and galactosidase-labelled anti-IgE. The highest number of detected allergens in the immunoblotting pattern was found in the presence of 50% glycerol at +6 degrees C. The most important allergen of C. albicans, the 46 kD protein allergen was stable up to 10 weeks at +6 degrees C in the presence of 50% glycerol but thereafter began to lose its IgE-binding capacity. After 30 weeks more than 50% of the IgE binding had disappeared. The 27 kD protein, another important allergen, was also labile but retained the allergenicity better than the 46 kD one. The 29 kD protein allergen was stable at all storage conditions, except +37 degrees C tested even after one year. More than 6 months storage at +6 degrees C or higher temperature is, however, unacceptable even in the presence of the 50% glycerol. These findings have particular importance in the diagnosis and treatment of allergic diseases.

  2. Candida albicans keratitis modified by steroid application

    Directory of Open Access Journals (Sweden)

    Kaoru Araki-Sasaki

    2009-02-01

    Full Text Available Kaoru Araki-Sasaki1, Hiroko Sonoyama1, Tsutomu Kawasaki1, Nariyasu Kazama1, Hidenao Ideta1, Yoshitsugu Inoue21Ideta Eye Hospital, Kumamoto City, Kumamoto, Japan; 2Department of Ophthalmology, Tottori University, Koyama-Minami, Tottori, Japan Abstract: The paper reports on Candida albicans ocular infection modified by steroid eye drops. A 74-year-old male complained of conjunctival injection and pain in his right eye three months after pterygium and cataract surgery. After treatment with antibiotics and steroid eye drops for three days, he was referred to our hospital. Clear localized corneal endothelial plaque with injection of ciliary body was observed. No erosion of the corneal epithelium, or infiltration of stromal edema was observed, suggesting that the pathological organism derived from the intracameral region. Because ocular infection was suspected, steroid eye drops were stopped, which led immediately to typical infectious keratitis in the pathological region, with epithelial erosion, fluffy abscess, stromal infiltration, and edema. For diagnostic purposes, the plaque was surgically removed with forceps and the anterior chamber was irrigated with antibiotics. The smear and culture examination from the plaque revealed C. albicans surrounded by neutrophils. However, aqueous fluid and fibrous tissue after gonio procedure contained no mycotic organisms. Topical fluconazole, micafungin, and pimaricin with oral itraconazole (150 mg/day were effective. Special attention is needed when prescribing steroid eye drops to treat corneal disease especially postoperatively. Diagnosing infectious keratitis is sometimes difficult because of modification by some factors, such as postoperative conditions, scarring, and drug-induced masking. Here, we report on mycotic keratitis modified by postoperative steroid administration. Keywords: Candida albicans, cataract surgery, steroid, mycotic keratitis

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Pei-Wen Tsai

    2017-12-01

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

  5. Rapid identification of Candida albicans by using Albicans ID and fluoroplate agar plates.

    OpenAIRE

    Rousselle, P.; Freydiere, A. M.; Couillerot, P J; De Montclos, H.; Gille, Y.

    1994-01-01

    Two commercially available agar media, Albicans ID and Fluoroplate, that use a chromogenic or a fluorogenic substrate for the detection and identification of Candida albicans were evaluated. From 1,006 clinical samples containing 723 yeast strains, 352 C. albicans strains were detected with either of the two media. The sensitivity of each of the two media was 93.8% and the specificity was 98.6%, with five false-positive reactions for Candida tropicalis and no false-negative reactions.

  6. Identification and characterization of a complete carnitine biosynthesis pathway in Candida albicans

    NARCIS (Netherlands)

    Strijbis, Karin; van Roermund, Carlo W. T.; Hardy, Guy P.; van den Burg, Janny; Bloem, Karien; de Haan, Jolanda; van Vlies, Naomi; Wanders, Ronald J. A.; Vaz, Frédéric M.; Distel, Ben

    2009-01-01

    Carnitine is an essential metabolite that enables intracellular transport of fatty acids and acetyl units. Here we show that the yeast Candida albicans can synthesize carnitine de novo, and we identify the 4 genes of the pathway. Null mutants of orf19.4316 (trimethyllysine dioxygenase), orf19.6306

  7. Th17 cells in immunity to Candida albicans

    National Research Council Canada - National Science Library

    Hernández-Santos, Nydiaris; Gaffen, Sarah L

    2012-01-01

    .... Many of these studies have focused on the most common human fungal pathogen, Candida albicans, which is typically a commensal microbe in healthy individuals but causes various disease manifestations...

  8. Influence of Candida krusei and Candida glabrata on Candida albicans gene expression in in vitro biofilms.

    Science.gov (United States)

    Barros, Patrícia Pimentel; Ribeiro, Felipe Camargo; Rossoni, Rodnei Dennis; Junqueira, Juliana Campos; Jorge, Antonio Olavo Cardoso

    2016-04-01

    The present study aimed to evaluate the interactions between the species Candida albicans, Candida krusei and Candida glabrata in monotypic and mixed biofilm models formed in vitro as well as the relative expression of the ALS1, ALS3, HWP1, BCR1, EFG1, TEC1, SAP5, PLB2 and LIP9 genes. Mixed (C. albicans/C. krusei and C. albicans/C. glabrata) and monotypic biofilms were cultured for 0, 12 and 24h. Gene expression was analyzed in the same biofilm model in which the number of CFU/mL was counted. The C. albicans CFU/mL values were lower at the 12 and 24h time points in the mixed biofilms compared with the monotypic biofilms, and decreases of 56.23% and 64.4% in C. albicans were observed when this species was associated with C. glabrata and C. krusei, respectively. In the presence of C. krusei, the expression of the ALS3, HWP1, BCR1, EFG1 and TEC1 genes of C. albicans was completely inhibited, indicating both transcriptome and the phenotypic antagonism between these two species, but genes related to the secretion of enzymes were stimulated. In the presence of C. glabrata, C. albicans showed a similar gene expression profile to that obtained in association with C. krusei, though it was altered to a lesser degree. We conclude that C. krusei and C. glabrata may alter or inhibit the mechanisms involved in the in vitro adherence and formation of C. albicans biofilms, influencing the pathogenicity of this species and suggesting a competitive interaction with C. krusei and C. glabrata in biofilm formation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. 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. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Interspecies Interactions between Clostridium difficile and Candida albicans

    NARCIS (Netherlands)

    van Leeuwen, P.T.; van der Peet, J.M.; Bikker, F.J.; Hoogenkamp, M.A.; Oliveira Paiva, A.M.; Kostidis, S.; Mayboroda, O.A.; Smits, W.K.; Krom, B.P.

    2016-01-01

    The facultative anaerobic polymorphic fungus Candida albicans and the strictly anaerobic Gram-positive bacterium Clostridium difficile are two opportunistic pathogens residing in the human gut. While a few studies have focused on the prevalence of C. albicans in C. difficile-infected patients, the

  11. Incidence Of Candida Albicans Infection Among Women Having ...

    African Journals Online (AJOL)

    Conclusion: It can be said that Candia albicans is one a common organism that cause vaginal discharge and itching among women, especially pregnant women in our environment. Keywords: Candida albicans, vaginal discharge, women and high vaginal swab. Tropical Journal of Medical Research Vol. 11 (2) 2007: pp.

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

    NARCIS (Netherlands)

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

    2009-01-01

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

  13. Elderly nutritional status effection salivary anticandidal capacity against Candida albicans

    OpenAIRE

    Puspitawati, Ria; Soedarsono, Nurtami; Putri, Elisabeth A; Putri, Anissha D; Bachtiar, Boy M

    2011-01-01

    Background: Elderly often suffer malnutrition and oral candidiasis. Candida albicans (C. albicans) which is the most prominent cause of oral candidiasis, is one of commensal oral micro-flora. Nutritional status affect the characteristic of saliva. Saliva is the regulator in the development of C. albicans from comensal into pathogen. Purpose: The purpose of this study was to determining the correlation between elderly nutritional status with salivary total protein and its activity in inhibitin...

  14. 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.

    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

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

    NARCIS (Netherlands)

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

    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

  16. Adaptation of Candida albicans to Reactive Sulfur Species.

    Science.gov (United States)

    Chebaro, Yasmin; Lorenz, Michael; Fa, Alice; Zheng, Rui; Gustin, Michael

    2017-05-01

    Candida albicans is an opportunistic fungal pathogen that is highly resistant to different oxidative stresses. How reactive sulfur species (RSS) such as sulfite regulate gene expression and the role of the transcription factor Zcf2 and the sulfite exporter Ssu1 in such responses are not known. Here, we show that C. albicans specifically adapts to sulfite stress and that Zcf2 is required for that response as well as induction of genes predicted to remove sulfite from cells and to increase the intracellular amount of a subset of nitrogen metabolites. Analysis of mutants in the sulfate assimilation pathway show that sulfite conversion to sulfide accounts for part of sulfite toxicity and that Zcf2-dependent expression of the SSU1 sulfite exporter is induced by both sulfite and sulfide. Mutations in the SSU1 promoter that selectively inhibit induction by the reactive nitrogen species (RNS) nitrite, a previously reported activator of SSU1, support a model for C. albicans in which Cta4-dependent RNS induction and Zcf2-dependent RSS induction are mediated by parallel pathways, different from S. cerevisiae in which the transcription factor Fzf1 mediates responses to both RNS and RSS. Lastly, we found that endogenous sulfite production leads to an increase in resistance to exogenously added sulfite. These results demonstrate that C. albicans has a unique response to sulfite that differs from the general oxidative stress response, and that adaptation to internal and external sulfite is largely mediated by one transcription factor and one effector gene. Copyright © 2017 by the Genetics Society of America.

  17. 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.

  18. Bacterial GtfB Augments Candida albicans Accumulation in Cross-Kingdom Biofilms.

    Science.gov (United States)

    Ellepola, K; Liu, Y; Cao, T; Koo, H; Seneviratne, C J

    2017-09-01

    Streptococcus mutans is a biofilm-forming oral pathogen commonly associated with dental caries. Clinical studies have shown that S. mutans is often detected with Candida albicans in early childhood caries. Although the C. albicans presence has been shown to enhance bacterial accumulation in biofilms, the influence of S. mutans on fungal biology in this mixed-species relationship remains largely uncharacterized. Therefore, we aimed to investigate how the presence of S. mutans influences C. albicans biofilm development and coexistence. Using a newly established haploid biofilm model of C. albicans, we found that S. mutans augmented haploid C. albicans accumulation in mixed-species biofilms. Similarly, diploid C. albicans also showed enhanced biofilm formation in the presence of S. mutans. Surprisingly, the presence of S. mutans restored the biofilm-forming ability of C. albicans bcr1Δ mutant and bcr1Δ/Δ mutant, which is known to be severely defective in biofilm formation when grown as single species. Moreover, C. albicans hyphal growth factor HWP1 as well as ALS1 and ALS3, which are also involved in fungal biofilm formation, were upregulated in the presence of S. mutans. Subsequently, we found that S. mutans-derived glucosyltransferase B (GtfB) itself can promote C. albicans biofilm development. Interestingly, GtfB was able to increase the expression of HWP1, ALS1, and ALS3 genes in the C. albicans diploid wild-type SC5314 and bcr1Δ/Δ, leading to enhanced fungal biofilms. Hence, the present study demonstrates that a bacterial exoenzyme (GtfB) augments the C. albicans counterpart in mixed-species biofilms through a BCR1-independent mechanism. This novel finding may explain the mutualistic role of S. mutans and C. albicans in cariogenic biofilms.

  19. Candida albicans commensalism in the gastrointestinal tract

    National Research Council Canada - National Science Library

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

    2015-01-01

    ... 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...

  20. Identification and functional characterization of mitochondrial carrier Mrs4 in Candida albicans.

    Science.gov (United States)

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

    2012-11-01

    Iron is an essential nutrient required for the growth and metabolism in Candida albicans. Here, we for the first time identified Mrs4 as a new member of mitochondrial carrier family in C. albicans. Our experiments revealed that C. albicans Mrs4 (CaMrs4) is localized to the mitochondria and required for mitochondrial morphology. We found that CaMrs4 is required for cell growth, and the mrs4Δ/Δ mutant showed a more severe growth defect in iron deficiency. Deletion of MRS4 affected cellular iron content by altering the expression of iron regulon genes in C. albicans, such as AFT2, SMF3, FTR1 and ISU1. Candida albicans Aft2 factor functions as a negative regulator of MRS4 expression through the CACCC Aft-type sequence in a gene dose-dependent fashion. In addition, the mrs4Δ/Δ mutant exhibited hypersensitivity to oxidants and most metal ions, but decreased sensitivity to cobalt. Exogenous iron could suppress the sensitivity of the mrs4Δ/Δ mutant to oxidants and most metal ions, suggesting that the role of CaMrs4 is partially mediated by iron availability. Furthermore, deletion of MRS4 resulted in delayed filamentation under tested conditions. Taken together, these findings characterize a new mitochondrial carrier and provide a novel insight into the role of CaMrs4 in mitochondrial function. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  1. Global Identification of Biofilm-Specific Proteolysis in Candida albicans

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    Michael B. Winter

    2016-09-01

    Full Text Available Candida albicans is a fungal species that is part of the normal human microbiota and also an opportunistic pathogen capable of causing mucosal and systemic infections. C. albicans cells proliferate in a planktonic (suspension state, but they also form biofilms, organized and tightly packed communities of cells attached to a solid surface. Biofilms colonize many niches of the human body and persist on implanted medical devices, where they are a major source of new C. albicans infections. Here, we used an unbiased and global substrate-profiling approach to discover proteolytic activities produced specifically by C. albicans biofilms, compared to planktonic cells, with the goal of identifying potential biofilm-specific diagnostic markers and targets for therapeutic intervention. This activity-based profiling approach, coupled with proteomics, identified Sap5 (Candidapepsin-5 and Sap6 (Candidapepsin-6 as major biofilm-specific proteases secreted by C. albicans. Fluorogenic peptide substrates with selectivity for Sap5 or Sap6 confirmed that their activities are highly upregulated in C. albicans biofilms; we also show that these activities are upregulated in other Candida clade pathogens. Deletion of the SAP5 and SAP6 genes in C. albicans compromised biofilm development in vitro in standard biofilm assays and in vivo in a rat central venous catheter biofilm model. This work establishes secreted proteolysis as a promising enzymatic marker and potential therapeutic target for Candida biofilm formation.

  2. Property differences among the four major Candida albicans strain clades.

    Science.gov (United States)

    MacCallum, Donna M; Castillo, Luis; Nather, Kerstin; Munro, Carol A; Brown, Alistair J P; Gow, Neil A R; Odds, Frank C

    2009-03-01

    A selection of 43 Candida albicans isolates, chosen to represent the four major strain clades of the species and also intraclade diversity, was screened for their virulence in the murine intravenous challenge model of C. albicans infection, for a range of properties measurable in vitro that might relate to virulence, and for the numbers of midrepeat sequences in genes of the ALS and HYR families. Heterozygosity at the mating type locus and low whole-cell acid phosphatase activity and growth rate at 40 degrees C were found to be significantly positively associated with the most virulent isolates. Acid phosphatase activity and growth in 2 M NaCl were statistically significant variables between clades by univariate analysis. Isolates in different clades also differed significantly in midrepeat sequence alleles of ALS2, ALS4, ALS6, ALS7, ALS9, HYR1, and HYR2. There was no association between the midrepeat alleles of any ALS or HYR gene and the virulence of isolates to mice. Genome-wide transcript profiles of 20 isolates (5 per clade) grown under two conditions showed considerable variation between individual isolates, but only a small number of genes showed statistically significant differential gene expression between clades. Analysis of the expression profiles by overall strain virulence revealed 18 open reading frames differing significantly between isolates of high, intermediate, and low virulence. Four of these genes encoded functions related to phosphate uptake and metabolism. This finding and the significant association between whole-cell acid phosphatase activity and virulence led us to disrupt PHO100, which encodes a predicted periplasmic acid phosphatase. The pho100Delta mutant was mildly but significantly attenuated in terms of survival curves in the mouse model. The study has extended the range of properties known to differ between C. albicans clades and suggests a possible but minor role of phosphate metabolism in the virulence of the species.

  3. Candida dubliniensis and Candida albicans differentiation by colony morphotype in Sabouraud-triphenyltetrazolium agar.

    Science.gov (United States)

    Gamarra, Soledad; Mancilla, Estefanía; Dudiuk, Catiana; Garcia-Effron, Guillermo

    2015-01-01

    Candida dubliniensis is a germ tube and chlamydoconidia producing Candida species that may be misidentified as Candida albicans. Molecular-based methods are the most reliable techniques for C. albicans and C. dubliniensis differentiation. However, accurate, quick and inexpensive phenotypic tests are needed to be used in low-complexity mycology laboratories. To evaluate colony morphotypes on Sabouraud-triphenyltetrazolium agar as a tool for C. dubliniensis and C. albicans differentiation. The morphology of 126 C. albicans and C. dubliniensis strains was evaluated and compared with their identification by molecular methods. The method showed 100% sensitivity and specificity when color and the presence or absence of large white mycelial halo was evaluated. Colony morphotype on Sabouraud-triphenyltetrazolium agar should be considered as a new tool to differentiate C. dubliniensis and C. albicans. Copyright © 2013 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

  4. Interactions of Candida albicans with host epithelial surfaces

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    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.

  5. Flavodoxin-Like Proteins Protect Candida albicans from Oxidative Stress and Promote Virulence.

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    Lifang Li

    2015-09-01

    Full Text Available The fungal pathogen Candida albicans causes lethal systemic infections in humans. To better define how pathogens resist oxidative attack by the immune system, we examined a family of four Flavodoxin-Like Proteins (FLPs in C. albicans. In agreement with previous studies showing that FLPs in bacteria and plants act as NAD(PH quinone oxidoreductases, a C. albicans quadruple mutant lacking all four FLPs (pst1Δ, pst2Δ, pst3Δ, ycp4Δ was more sensitive to benzoquinone. Interestingly, the quadruple mutant was also more sensitive to a variety of oxidants. Quinone reductase activity confers important antioxidant effects because resistance to oxidation was restored in the quadruple mutant by expressing either Escherichia coli wrbA or mammalian NQO1, two distinct types of quinone reductases. FLPs were detected at the plasma membrane in C. albicans, and the quadruple mutant was more sensitive to linolenic acid, a polyunsaturated fatty acid that can auto-oxidize and promote lipid peroxidation. These observations suggested that FLPs reduce ubiquinone (coenzyme Q, enabling it to serve as an antioxidant in the membrane. In support of this, a C. albicans coq3Δ mutant that fails to synthesize ubiquinone was also highly sensitive to oxidative stress. FLPs are critical for survival in the host, as the quadruple mutant was avirulent in a mouse model of systemic candidiasis under conditions where infection with wild type C. albicans was lethal. The quadruple mutant cells initially grew well in kidneys, the major site of C. albicans growth in mice, but then declined after the influx of neutrophils and by day 4 post-infection 33% of the mice cleared the infection. Thus, FLPs and ubiquinone are important new antioxidant mechanisms that are critical for fungal virulence. The potential of FLPs as novel targets for antifungal therapy is further underscored by their absence in mammalian cells.

  6. 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

    2016-01-01

    abstract 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

  7. Three Candida albicans potassium uptake systems differ in their ability to provide Saccharomyces cerevisiae trk1trk2 mutants with necessary potassium

    Czech Academy of Sciences Publication Activity Database

    Elicharová, Hana; Hušeková, Barbora; Sychrová, Hana

    2016-01-01

    Roč. 16, č. 4 (2016), fow039 ISSN 1567-1356 R&D Projects: GA ČR(CZ) GAP302/12/1151; GA ČR(CZ) GA16-03398S EU Projects: European Commission(XE) 606786 - ImResFun Institutional support: RVO:67985823 Keywords : Candida * potassium uptake * Hak1 transporter * Trk1 transporter * Acu1 ATPase * cation homeostasis Subject RIV: EE - Microbiology, Virology Impact factor: 3.299, year: 2016

  8. Candida albicans versus non-albicans bloodstream infections: the comparison of risk factors and outcome.

    Science.gov (United States)

    Chi, Hung-Wei; Yang, Ya-Sung; Shang, Shi-Ta; Chen, Ke-Hung; Yeh, Kuo-Ming; Chang, Feng-Yee; Lin, Jung-Chung

    2011-10-01

    Candidemia caused by non-albicans Candida spp. is of special concern because of its high drug resistance and increase in prevalence. In clinical practice, early identification of non-albicans candidemia is crucial. We investigated the outcome in patients with candidemia caused by Candida albicans and Candida non-albicans. We retrospectively evaluated candidemic patients from October 2007 to July 2009. Underlying diseases, predisposing factors, laboratory data, and outcome were analyzed. One hundred and eight patients of candidemia were enrolled. Candida albicans and non-albicans spp. were responsible for 56.5% (61 of 108) and 43.5% (47 of 108) of candidemia cases, respectively. Among patients with non-albicans candidemia, significantly more patients had neutropenia (p=0.001) and less patients had candiduria (p=0.001) and intensive care unit stay (p=0.002) in comparison with those with C albicans candidemia. All-cause Day 7 mortality was high in both C albicans and non-albicans spp. candidemia [44.3% (27 of 61) vs. 29.8% (14 of 47)]. Multivariate analysis revealed that poor renal function (odds ratio, 1.035; 95% confidence interval, 1.001-1.071; p=0.04) and shock (odds ratio, 19.4; 95% confidence interval, 2.53-149.5; p=0.004) are independent risk factors for fatal candidemia. The outcome of candidemia was poor. The identified risk factors may help us to differentiate fatal candidemia in early infection. Copyright © 2011. Published by Elsevier B.V.

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

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    Demet Toprak

    2015-01-01

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

  10. Global Identification of Biofilm-Specific Proteolysis in Candida albicans.

    Science.gov (United States)

    Winter, Michael B; Salcedo, Eugenia C; Lohse, Matthew B; Hartooni, Nairi; Gulati, Megha; Sanchez, Hiram; Takagi, Julie; Hube, Bernhard; Andes, David R; Johnson, Alexander D; Craik, Charles S; Nobile, Clarissa J

    2016-09-13

    Candida albicans is a fungal species that is part of the normal human microbiota and also an opportunistic pathogen capable of causing mucosal and systemic infections. C. albicans cells proliferate in a planktonic (suspension) state, but they also form biofilms, organized and tightly packed communities of cells attached to a solid surface. Biofilms colonize many niches of the human body and persist on implanted medical devices, where they are a major source of new C. albicans infections. Here, we used an unbiased and global substrate-profiling approach to discover proteolytic activities produced specifically by C. albicans biofilms, compared to planktonic cells, with the goal of identifying potential biofilm-specific diagnostic markers and targets for therapeutic intervention. This activity-based profiling approach, coupled with proteomics, identified Sap5 (Candidapepsin-5) and Sap6 (Candidapepsin-6) as major biofilm-specific proteases secreted by C. albicans Fluorogenic peptide substrates with selectivity for Sap5 or Sap6 confirmed that their activities are highly upregulated in C. albicans biofilms; we also show that these activities are upregulated in other Candida clade pathogens. Deletion of the SAP5 and SAP6 genes in C. albicans compromised biofilm development in vitro in standard biofilm assays and in vivo in a rat central venous catheter biofilm model. This work establishes secreted proteolysis as a promising enzymatic marker and potential therapeutic target for Candida biofilm formation. Biofilm formation by the opportunistic fungal pathogen C. albicans is a major cause of life-threatening infections. This work provides a global characterization of secreted proteolytic activity produced specifically by C. albicans biofilms. We identify activity from the proteases Sap5 and Sap6 as highly upregulated during C. albicans biofilm formation and develop Sap-cleavable fluorogenic substrates that enable the detection of biofilms from C. albicans and also

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

    Science.gov (United States)

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

    2016-11-01

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

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

    NARCIS (Netherlands)

    Jackson, A.P.; Gamble, J.A.; Yeomans, T.; Moran, G.P.; Saunders, D.; Harris, D.; Aslett, M.; Barrell, J.F.; Butler, G.; Citiulo, F.; Coleman, D.C.; de Groot, P.W.J.; Goodwin, T.J.; Quail, M.A.; McQuillan, J.; Munro, C.A.; Pain, A.; Poulter, R.T.; Rajandream, M-A.; Renauld, H.; Spiering, M.J.; Tivey, A.; Gow, N.A.R.; Barrell, B.; Sullivan, D.J.; Berriman, M.

    2009-01-01

    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

  13. 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

  14. Candida krusei and Candida glabrata reduce the filamentation of Candida albicans by downregulating expression of HWP1 gene.

    Science.gov (United States)

    de Barros, Patrícia Pimentel; Freire, Fernanda; Rossoni, Rodnei Dennis; Junqueira, Juliana Campos; Jorge, Antonio Olavo Cardoso

    2017-07-01

    Pathogenicity of Candida albicans is associated with its capacity switch from yeast-like to hyphal growth. The hyphal form is capable to penetrate the epithelial surfaces and to damage the host tissues. Therefore, many investigations have focused on mechanisms that control the morphological transitions of C. albicans. Recently, certain studies have showed that non-albicans Candida species can reduce the capacity of C. albicans to form biofilms and to develop candidiasis in animal models. Then, the objective of this study was to evaluate the effects of Candida krusei and Candida glabrata on the morphogenesis of C. albicans. Firstly, the capacity of reference and clinical strains of C. albicans in forming hyphae was tested in vitro. After that, the expression of HWP1 (hyphal wall protein 1) gene was determined by quantitative real-time PCR (polymerase chain reaction) assay. For both reference and clinical strains, a significant inhibition of the hyphae formation was observed when C. albicans was incubated in the presence of C. krusei or C. glabrata compared to the control group composed only by C. albicans. In addition, the culture mixed of C. albicans-C. krusei or C. albicans-C. glabrata reduced significantly the expression of HWP1 gene of C. albicans in relation to single cultures of this specie. In both filamentation and gene expression assays, C. krusei showed the higher inhibitory activity on the morphogenesis of C. albicans compared to C. glabrata. C. krusei and C. glabrata are capable to reduce the filamentation of C. albicans and consequently decrease the expression of the HWP1 gene.

  15. Simplified sunflower (Helianthus annuus) seed agar for differentiation of Candida dubliniensis from Candida albicans.

    Science.gov (United States)

    Khan, Z U; Ahmad, S; Mokaddas, E; Chandy, R

    2004-06-01

    This study evaluated sunflower (Helianthus annuus) seed agar (SSA) for differentiation of Candida dubliniensis from Candida albicans on the basis of colony characteristics and chlamydospore production. Simplified SSA without creatinine and KH(2)PO(4) was also used. On both media, C. dubliniensis isolates (n = 25) developed rough colonies and formed abundant chlamydospores after incubation for 24-48 h at 28 degrees C, while C. albicans isolates (n = 53) showed smooth colonies with no evidence of chlamydospore formation. Cryptococcus neoformans isolates (n = 10) formed brown colonies on both media. Simplified SSA offers a simple and inexpensive tool for presumptive differentiation of C. dubliniensis from C. albicans in clinical microbiology laboratories.

  16. Prevalence of yeast other than Candida albicans in denture wearers.

    Science.gov (United States)

    Cavaleiro, Inês; Proença, Luis; Félix, Sérgio; Salema-Oom, Madalena

    2013-07-01

    The isolation of yeast species other than Candida albicans from the oral mucosa has been increasing in frequency, suggesting that those may constitute emerging potential oral colonizers. The purpose of this work was to determine whether yeast species other than C. albicans are associated with factors related to wearing of dental prostheses. tRNA-PCR fingerprinting and sequencing of the 26S rDNA D1/D2 domain were used to identify all yeasts isolated from CHROMagar™ Candida cultures of oral swabs collected from 178 patients. Besides C. albicans, 13 other species were identified, corresponding to 34% of the yeast isolates. The majority of the non-C. albicans species were not detected as single colonizers but rather in co-colonization with one or two other yeasts, often with C. albicans. No significant associations were found with non-C. albicans species. On the contrary, the best-fitted logistic regression model predicts that either wearing a denture (adjusted odds = 4.6) or insufficient oral hygiene (adjusted odds = 2.3) are risks for colonization by yeast, in general. The colonization with non-C. albicans species and co-colonization were not independently associated with any of the analyzed host-related factors. In particular, neither wearing a removable denture nor being elderly were significant predictors. © 2012 by the American College of Prosthodontists.

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

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    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.

  18. 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.

    2014-01-01

    ABSTRACT 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. PMID:24736223

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

    Directory of Open Access Journals (Sweden)

    Swetha Tati

    2016-03-01

    Full Text Available 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.

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

    Science.gov (United States)

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

    2016-01-01

    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. PMID:27029023

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

    Directory of Open Access Journals (Sweden)

    Fabíola Silveira-Gomes

    2011-08-01

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

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

    Science.gov (United States)

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

    2011-01-01

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

  3. Candida albicans suppresses transcription of melanogenesis enzymes in cultured melanocytes.

    Science.gov (United States)

    Kippenberger, S; Bernd, A; Menzel, I; Loitsch, S; Ramirez-Bosca, A; Kaufmann, R

    1997-12-01

    Human skin can be colonized by different yeasts that may have an impact on skin pigmentation. In order to study this effect normal human melanocytes were cultured with different yeasts. Reverse transcription polymerase chain reaction (RT-PCR) analysis gives evidence that Candida albicans suppresses the transcription of melanogenesis enzymes.

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

    African Journals Online (AJOL)

    2016-06-24

    Jun 24, 2016 ... adhesion to dental restorative materials especially in people with weakened immune systems, neutropenia, and cancer. Evaluation of Candida Albicans Biofilm Formation on Various Dental. Restorative Material Surfaces. Address for correspondence: Dr. Nihal Belduz,. Department of Paediatric Dentistry, ...

  5. 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.

    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

  6. Genotyping Candida albicans from Candida Leukoplakia and Non-Candida Leukoplakia Shows No Enrichment of Multilocus Sequence Typing Clades but Enrichment of ABC Genotype C in Candida Leukoplakia

    OpenAIRE

    Abdulrahim, Mohammed H.; McManus, Brenda A.; Flint, Stephen R.; Coleman, David C.

    2013-01-01

    PUBLISHED Published: September 18th 2013 Oral leukoplakias are histopathologically-diagnosed as Candida leukoplakia or non-Candida leukoplakia by the presence or absence of hyphae in the superficial epithelium. Candida leukoplakia lesions have significantly increased malignant potential. Candida albicans is the most prevalent fungal species associated with oral leukoplakia and may contribute to malignant transformation of Candida leukoplakia. To date, no detailed population analysis of ...

  7. 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.

  8. Differentiation of Candida albicans, Candida glabrata, and Candida krusei by FT-IR and chemometrics by CHROMagar™ Candida.

    Science.gov (United States)

    Wohlmeister, Denise; Vianna, Débora Renz Barreto; Helfer, Virginia Etges; Calil, Luciane Noal; Buffon, Andréia; Fuentefria, Alexandre Meneghello; Corbellini, Valeriano Antonio; Pilger, Diogo André

    2017-10-01

    Pathogenic Candida species are detected in clinical infections. CHROMagar™ is a phenotypical method used to identify Candida species, although it has limitations, which indicates the need for more sensitive and specific techniques. Infrared Spectroscopy (FT-IR) is an analytical vibrational technique used to identify patterns of metabolic fingerprint of biological matrixes, particularly whole microbial cell systems as Candida sp. in association of classificatory chemometrics algorithms. On the other hand, Soft Independent Modeling by Class Analogy (SIMCA) is one of the typical algorithms still little employed in microbiological classification. This study demonstrates the applicability of the FT-IR-technique by specular reflectance associated with SIMCA to discriminate Candida species isolated from vaginal discharges and grown on CHROMagar™. The differences in spectra of C. albicans, C. glabrata and C. krusei were suitable for use in the discrimination of these species, which was observed by PCA. Then, a SIMCA model was constructed with standard samples of three species and using the spectral region of 1792-1561cm(-1). All samples (n=48) were properly classified based on the chromogenic method using CHROMagar™ Candida. In total, 93.4% (n=45) of the samples were correctly and unambiguously classified (Class I). Two samples of C. albicans were classified correctly, though these could have been C. glabrata (Class II). Also, one C. glabrata sample could have been classified as C. krusei (Class II). Concerning these three samples, one triplicate of each was included in Class II and two in Class I. Therefore, FT-IR associated with SIMCA can be used to identify samples of C. albicans, C. glabrata, and C. krusei grown in CHROMagar™ Candida aiming to improve clinical applications of this technique. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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. Fluconazole treatment of intrauterine Candida albicans infection in fetal sheep.

    Science.gov (United States)

    Maneenil, Gunlawadee; Payne, Matthew S; Senthamarai Kannan, Paranthaman; Kallapur, Suhas G; Kramer, Boris W; Newnham, John P; Miura, Yuichiro; Jobe, Alan H; Kemp, Matthew W

    2015-06-01

    Intrauterine Candida albicans infection causes severe fetal inflammatory responses and fetal injury in an ovine model. We hypothesized that intra-amniotic antifungal therapy with fluconazole would decrease the adverse fetal effects of intra-amniotic C. albicans in sheep. Sheep received an intra-amniotic injection of 10(7) colony-forming units C. albicans. After 2 d, animals were then randomized to: (i) intra-amniotic and fetal intraperitoneal saline with delivery after 24 h (3 d C. albicans group); (ii) intra-amniotic and fetal intraperitoneal injections of fluconazole with delivery after either 24 h (3 d C. albicans plus 1 d fluconazole group) or 72 h (5 d C. albicans plus 3 d fluconazole group). Controls received intra-amniotic injections of saline followed by intra-amniotic and fetal intraperitoneal fluconazole injections. Intra-amniotic C. albicans caused severe fetal inflammatory responses characterized by decreases in lymphocytes and platelets, an increase in posterior mediastinal lymph node weight and proinflammatory mRNA responses in the fetal lung, liver, and spleen. Fluconazole treatment temporarily decreased the pulmonary and chorioamnion inflammatory responses. The severe fetal inflammatory responses caused by intra-amniotic C. albicans infection were transiently decreased with fluconazole. A timely fetal delivery of antimicrobial agents may prevent fetal injury associated with intrauterine infection.

  11. Plasma-membrane Cnh1 Na+/H+ antiporter regulates potassium homeostasis in Candida albicans.

    Science.gov (United States)

    Kinclova-Zimmermannova, Olga; Sychrová, Hana

    2007-08-01

    The physiological role of Candida albicans Cnh1, a member of the Na+/H+ antiporter family, was characterized. Though CaCnh1p had broad substrate specificity and mediated efflux of at least four alkali metal cations upon heterologous expression in Saccharomyces cerevisiae, its presence in C. albicans cells was important especially for potassium homeostasis. In C. albicans, CaCnh1p tagged with GFP was localized in the plasma membrane of cells growing as both yeasts and hyphae. Deletion of CNH1 alleles did not affect tolerance to NaCl, LiCl or CsCl, but resulted in increased sensitivity to high external concentrations of KCl and RbCl. The potassium and rubidium tolerance of a cnh1 homozygous mutant was fully restored by reintegration of CNH1 into the genome. The higher sensitivity of the cnh1/cnh1 mutant to external KCl was caused by a lower K+ efflux from these cells. Together, the functional characterization of the CaCnh1 antiporter in C. albicans revealed that this antiporter plays a significant role in C. albicans physiology. It ensures potassium and rubidium tolerance and participates in the regulation of intracellular potassium content of C. albicans cells.

  12. Role of Candida albicans secreted aspartyl protease Sap9 in interkingdom biofilm formation.

    Science.gov (United States)

    Dutton, Lindsay C; Jenkinson, Howard F; Lamont, Richard J; Nobbs, Angela H

    2016-04-01

    The fungus Candida albicans colonizes oral cavity surfaces and is carried by up to 60% of human populations. Biofilm development by C. albicans may be modulated by oral streptococci, such as Streptococcus gordonii, S. oralis or S. mutans, so as to augment pathogenicity. In this study we sought to determine if the cell wall-associated secreted aspartyl proteinase Sap9 was necessary for hyphal adhesin functions associated with biofilm community development. A sap9Δ mutant of C. albicans SC5314 formed biofilms that were flatter, and contained fewer blastospores and more hyphal filaments than the parent strain. This phenotypic difference was accentuated under flow (shear) conditions and in the presence of S. gordonii. Dual-species biofilms of C. albicans sap9Δ with S. oralis, S. sanguinis, S. parasanguinis, S. mutans and Enterococcus faecalis all contained more matted hyphae and more bacteria bound to substratum compared to C. albicans wild type. sap9Δ mutant hyphae showed significantly increased cell surface hydrophobicity, ∼25% increased levels of binding C. albicans cell wall protein Als3, and reduced interaction with Eap1, implicating Sap9 in fungal cell-cell recognition. These observations suggest that Sap9 is associated with protein-receptor interactions between fungal cells, and with interkingdom communication in the formation of polymicrobial biofilm communities. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. MFS transportome of the human pathogenic yeast Candida albicans.

    Science.gov (United States)

    Gaur, Manisha; Puri, Nidhi; Manoharlal, Raman; Rai, Versha; Mukhopadhayay, Gauranga; Choudhury, Devapriya; Prasad, Rajendra

    2008-12-03

    The major facilitator superfamily (MFS) is one of the two largest superfamilies of membrane transporters present ubiquitously in bacteria, archaea, and eukarya and includes members that function as uniporters, symporters or antiporters. We report here the complete transportome of MFS proteins of a human pathogenic yeast Candida albicans. Computational analysis of C. albicans genome enabled us to identify 95 potential MFS proteins which clustered into 17 families using Saier's Transport Commission (TC) system. Among these SP, DHA1, DHA2 and ACS represented major families consisting of 22, 22, 9 and 16 members, respectively. Family designations in C. albicans were validated by subjecting Saccharomyces cerevisiae genome to TC system. Based on the published available genomics/proteomics data, 87 of the putative MFS genes of C. albicans were found to express either at mRNA or protein levels. We checked the expression of the remaining 8 genes by using RT-PCR and observed that they are not expressed under basal growth conditions implying that either these 8 genes are expressed under specific growth conditions or they may be candidates for pseudogenes. The in silico characterisation of MFS transporters in Candida albicans genome revealed a large complement of MFS transporters with most of them showing expression. Considering the clinical relevance of C. albicans and role of MFS members in antifungal resistance and nutrient transport, this analysis would pave way for identifying their physiological relevance.

  14. Candida albicans: A Model Organism for Studying Fungal Pathogens

    Science.gov (United States)

    Kabir, M. Anaul; Hussain, Mohammad Asif; Ahmad, Zulfiqar

    2012-01-01

    Candida albicans is an opportunistic human fungal pathogen that causes candidiasis. As healthcare has been improved worldwide, the number of immunocompromised patients has been increased to a greater extent and they are highly susceptible to various pathogenic microbes and C. albicans has been prominent among the fungal pathogens. The complete genome sequence of this pathogen is now available and has been extremely useful for the identification of repertoire of genes present in this pathogen. The major challenge is now to assign the functions to these genes of which 13% are specific to C. albicans. Due to its close relationship with yeast Saccharomyces cerevisiae, an edge over other fungal pathogens because most of the technologies can be directly transferred to C. albicans from S. cerevisiae and it is amenable to mutation, gene disruption, and transformation. The last two decades have witnessed enormous amount of research activities on this pathogen that leads to the understanding of host-parasite interaction, infections, and disease propagation. Clearly, C. albicans has emerged as a model organism for studying fungal pathogens along with other two fungi Aspergillus fumigatus and Cryptococcus neoformans. Understanding its complete life style of C. albicans will undoubtedly be useful for developing potential antifungal drugs and tackling Candida infections. This will also shed light on the functioning of other fungal pathogens. PMID:23762753

  15. Host response to Candida albicans bloodstream infection and sepsis

    Science.gov (United States)

    Duggan, Seána; Leonhardt, Ines; Hünniger, Kerstin; Kurzai, Oliver

    2015-01-01

    Candida albicans is a major cause of bloodstream infection which may present as sepsis and septic shock - major causes of morbidity and mortality world-wide. After invasion of the pathogen, innate mechanisms govern the early response. Here, we outline the models used to study these mechanisms and summarize our current understanding of innate immune responses during Candida bloodstream infection. This includes protective immunity as well as harmful responses resulting in Candida induced sepsis. Neutrophilic granulocytes are considered principal effector cells conferring protection and recognize C. albicans mainly via complement receptor 3. They possess a range of effector mechanisms, contributing to elimination of the pathogen. Neutrophil activation is closely linked to complement and modulated by activated mononuclear cells. A thorough understanding of these mechanisms will help in creating an individualized approach to patients suffering from systemic candidiasis and aid in optimizing clinical management. PMID:25785541

  16. 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

  17. Regulation of Candida albicans Interaction with Macrophages through the Activation of HOG Pathway by Genistein

    Directory of Open Access Journals (Sweden)

    Shuna Cui

    2016-01-01

    Full Text Available The severity of infections caused by Candida albicans, the most common opportunistic human fungal pathogen, needs rapid and effective antifungal treatments. One of the effective ways is to control the virulence factors of the pathogen. Therefore, the current study examined the effects of genistein, a natural isoflavone present in soybeans, on C. albicans. The genistein-treated C. albicans cells were then exposed to macrophages. Although no inhibition effect on the growth rates of C. albicans was noted an enhancement of the immune response to macrophages has been observed, indicated by phagocytosis and release of cytokines TNF-α and IL-10. The effect of genistein on the enhanced phagocytosis can be mimicked by the fungicides fludioxonil or iprodione, which inhibit the histidine kinase Cos1p and lead to activation of HOG pathway. The western blot results showed a clear phosphorylation of Hog1p in the wild type strain of C. albicans after incubation with genistein. In addition, effects of genistein on the phosphorylation of Hog1p in the histidine kinase mutants Δcos1 and Δsln1 were also observed. Our results thus indicate a new bio-activity of genistein on C. albicans by activation of the HOG pathway of the human pathogen C. albicans.

  18. 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.

  19. Prevalence of Candida albicans, Candida dubliniensis and Candida africana in pregnant women suffering from vulvovaginal candidiasis in Argentina.

    Science.gov (United States)

    Mucci, María Josefina; Cuestas, María Luján; Landanburu, María Fernanda; Mujica, María Teresa

    Vulvovaginal candidiasis (VVC) is a vulvovaginitis commonly diagnosed in gynecology care. In recent years, the taxonomy of the most important pathogenic Candida species, such as Candida albicans have undergone significant changes. This study examined the prevalence of C. albicans, Candida africana, and Candida dubliniensis in vaginal specimens from 210 pregnant women suffering from vulvovaginitis or having asymptomatic colonization. Phenotypic and molecular methods were used for the identification of the species. During the studied period, 55 isolates of Candida or other yeasts were obtained from specimens collected from 52 patients suffering from vulvovaginitis (24.8%). C. albicans was the predominant Candida species in 42 isolates (80.7%), either alone or in combination with other species of the genus (5.7%, n=3). Additionally, nine isolates of C. albicans (50%) were obtained from asymptomatic patients (n=18). C. dubliniensis was the causative agent in 2 (3.8%) cases of VVC, and was also isolated in one asymptomatic patient. Molecular assays were carried out using specific PCR to amplify the ACT1-associated intron sequence of C. dubliniensis. The amplification of the HWP1 gene also correctly identified isolates of the species C. albicans and C. dubliniensis. No C. africana was isolated in this work. Some C. albicans isolates were either homozygous or heterozygous at the HWP1 locus. The distribution of heterozygous and homozygous C. albicans isolates at the HWP1 locus was very similar among patients suffering from VVC and asymptomatic patients (p=0.897). The presence of C. albicans and C. dubliniensis, and the absence of C. africana in pregnant is noteworthy. Copyright © 2016 Asociación Española de Micología. Publicado por Elsevier España, S.L.U. All rights reserved.

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

    Science.gov (United States)

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

    2015-09-01

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

  1. Photoinactivation of single and mixed biofilms of Candida albicans and non-albicans Candida species using Phorodithazine®.

    Science.gov (United States)

    Carmello, Juliana Cabrini; Alves, Fernanda; Mima, Ewerton Garcia de Oliveira; Jorge, Janaina Habib; Bagnato, Vanderlei Salvador; Pavarina, Ana Cláudia

    2017-03-01

    This study evaluated the effectiveness of antimicrobial photodynamic therapy (aPDT) mediated by Photodithazine® (PDZ) formulated in hydrogel, in the inactivation of mono and duo-species biofilms of Candida albicans, Candida glabrata and Candida tropicalis. Standardized suspensions of each strain were prepared and after biofilm formation, mono-species were treated with 150 and 175mg/L of PDZ for 20min (pre-irradiation time), and exposed to LED light at a dose of 37.5J/cm2 (660nm). The duo-species biofilms (C. albicans+C. glabrata and C. albicans+C. tropicalis) were treated with 150mg/L of PDZ and light. Additional samples were treated with PDZ or light only, and the control did not receive any treatment. Next, microbiological evaluation was performed by spreading the cells on Sabouraud Dextrose Agar and CHROMagar Candida for colony forming units (CFU/mL). Moreover, the total biomass of biofilm was verified using the crystal violet staining assay (CV). The data were submitted to ANOVA and Tukey post-hoc (α=0.05). The use of PDZ 150mg/L promoted a reduction of 1.0, 1.2, 1.5 log10 in the viability of C. glabrata, C. albicans and C. tropicalis, respectively. The same concentration reduced in 1.0 log10 the viability of each species grown as duo-species biofilms. The crystal violet assay showed that the use of 150mg/L reduced 24.4%, 39.2% and 43.7% of the total biomass of C. albicans, C. tropicalis and C. glabrata, respectively. aPDT did not reduce the total biomass to the duo-species biofilms. Thus, PDZ-mediated aPDT was more effective in the inactivation of mono-species biofilms of Candida spp. compared with duo-species biofilm. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Endang W. Bachtiar

    2014-07-01

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

  3. 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.

  4. Genotyping Candida albicans from Candida Leukoplakia and Non-Candida Leukoplakia Shows No Enrichment of Multilocus Sequence Typing Clades but Enrichment of ABC Genotype C in Candida Leukoplakia

    Science.gov (United States)

    Flint, Stephen R.; Coleman, David C.

    2013-01-01

    Oral leukoplakias are histopathologically-diagnosed as Candida leukoplakia or non-Candida leukoplakia by the presence or absence of hyphae in the superficial epithelium. Candida leukoplakia lesions have significantly increased malignant potential. Candida albicans is the most prevalent fungal species associated with oral leukoplakia and may contribute to malignant transformation of Candida leukoplakia. To date, no detailed population analysis of C. albicans isolates from oral leukoplakia patients has been undertaken. This study investigated whether specific C. albicans genotypes were associated with Candida leukoplakia and non-Candida leukoplakia in a cohort of Irish patients. Patients with histopathologically-defined Candida leukoplakia (n = 31) or non-Candida leukoplakia (n = 47) were screened for Candida species by culture of oral rinse and lesional swab samples. Selected C. albicans isolates from Candida leukoplakia patients (n = 25), non-Candida leukoplakia patients (n = 19) and oral carriage isolates from age and sex matched healthy subjects without leukoplakia (n = 34) were subjected to multilocus sequence typing (MLST) and ABC genotyping. MLST revealed that the clade distribution of C. albicans from both Candida leukoplakia and non-Candida leukoplakia lesions overlapped with the corresponding clade distributions of oral carriage isolates and global reference isolates from the MLST database indicating no enrichment of leukoplakia-associated clones. Oral leukoplakia isolates were significantly enriched with ABC genotype C (12/44, 27.3%), particularly Candida leukoplakia isolates (9/25, 36%), relative to oral carriage isolates (3/34, 8.8%). Genotype C oral leukoplakia isolates were distributed in MLST clades 1,3,4,5,8,9 and 15, whereas genotype C oral carriage isolates were distributed in MLST clades 4 and 11. PMID:24058485

  5. Genotyping Candida albicans from Candida leukoplakia and non-Candida leukoplakia shows no enrichment of multilocus sequence typing clades but enrichment of ABC genotype C in Candida leukoplakia.

    Directory of Open Access Journals (Sweden)

    Mohammed H Abdulrahim

    Full Text Available Oral leukoplakias are histopathologically-diagnosed as Candida leukoplakia or non-Candida leukoplakia by the presence or absence of hyphae in the superficial epithelium. Candida leukoplakia lesions have significantly increased malignant potential. Candida albicans is the most prevalent fungal species associated with oral leukoplakia and may contribute to malignant transformation of Candida leukoplakia. To date, no detailed population analysis of C. albicans isolates from oral leukoplakia patients has been undertaken. This study investigated whether specific C. albicans genotypes were associated with Candida leukoplakia and non-Candida leukoplakia in a cohort of Irish patients. Patients with histopathologically-defined Candida leukoplakia (n = 31 or non-Candida leukoplakia (n = 47 were screened for Candida species by culture of oral rinse and lesional swab samples. Selected C. albicans isolates from Candida leukoplakia patients (n = 25, non-Candida leukoplakia patients (n = 19 and oral carriage isolates from age and sex matched healthy subjects without leukoplakia (n = 34 were subjected to multilocus sequence typing (MLST and ABC genotyping. MLST revealed that the clade distribution of C. albicans from both Candida leukoplakia and non-Candida leukoplakia lesions overlapped with the corresponding clade distributions of oral carriage isolates and global reference isolates from the MLST database indicating no enrichment of leukoplakia-associated clones. Oral leukoplakia isolates were significantly enriched with ABC genotype C (12/44, 27.3%, particularly Candida leukoplakia isolates (9/25, 36%, relative to oral carriage isolates (3/34, 8.8%. Genotype C oral leukoplakia isolates were distributed in MLST clades 1,3,4,5,8,9 and 15, whereas genotype C oral carriage isolates were distributed in MLST clades 4 and 11.

  6. Genotyping Candida albicans from Candida leukoplakia and non-Candida leukoplakia shows no enrichment of multilocus sequence typing clades but enrichment of ABC genotype C in Candida leukoplakia.

    Science.gov (United States)

    Abdulrahim, Mohammed H; McManus, Brenda A; Flint, Stephen R; Coleman, David C

    2013-01-01

    Oral leukoplakias are histopathologically-diagnosed as Candida leukoplakia or non-Candida leukoplakia by the presence or absence of hyphae in the superficial epithelium. Candida leukoplakia lesions have significantly increased malignant potential. Candida albicans is the most prevalent fungal species associated with oral leukoplakia and may contribute to malignant transformation of Candida leukoplakia. To date, no detailed population analysis of C. albicans isolates from oral leukoplakia patients has been undertaken. This study investigated whether specific C. albicans genotypes were associated with Candida leukoplakia and non-Candida leukoplakia in a cohort of Irish patients. Patients with histopathologically-defined Candida leukoplakia (n = 31) or non-Candida leukoplakia (n = 47) were screened for Candida species by culture of oral rinse and lesional swab samples. Selected C. albicans isolates from Candida leukoplakia patients (n = 25), non-Candida leukoplakia patients (n = 19) and oral carriage isolates from age and sex matched healthy subjects without leukoplakia (n = 34) were subjected to multilocus sequence typing (MLST) and ABC genotyping. MLST revealed that the clade distribution of C. albicans from both Candida leukoplakia and non-Candida leukoplakia lesions overlapped with the corresponding clade distributions of oral carriage isolates and global reference isolates from the MLST database indicating no enrichment of leukoplakia-associated clones. Oral leukoplakia isolates were significantly enriched with ABC genotype C (12/44, 27.3%), particularly Candida leukoplakia isolates (9/25, 36%), relative to oral carriage isolates (3/34, 8.8%). Genotype C oral leukoplakia isolates were distributed in MLST clades 1,3,4,5,8,9 and 15, whereas genotype C oral carriage isolates were distributed in MLST clades 4 and 11.

  7. EVALUATION OF DIFFERENT MEDIA FOR GERM TUBE PRODUCTION OF CANDIDA ALBICANS AND CANDIDA DUBLINIENSIS

    OpenAIRE

    Deorukhkar, Sachin Chandrakant; Saini, Santosh; Jadhav, Pradnya A

    2012-01-01

    Background: The germ tube production in serum is a rapid method for identification of Candida. Because of the time required to prepare human serum and inherent safety problems concerned with its use, many laboratories have started using non human serum germ tube media. The objective of this study was to evaluate different media for germ tube production of C. albicans and C. dubliniensisMaterial and Methods: 132 C. albicans and 30 C. dubliniensis isolates were tested for germ tube production i...

  8. [Phagocytosis and lysis of Candida albicans and Candida pseudotropicalis by polymorphonuclear neutrophils of Hansen's disease patients].

    Science.gov (United States)

    Fliess, E L; Comesaña, G; Carrara, R C; España, A

    1981-12-01

    The phagocytosis and lysis of Candida albicans and Candida pseudotropicalis by human neutrophils were examined in 43 hanseniasis patients (19 quiescent virchowians, 12 reactional virchowians and 12 tuberculoid patients) and 15 healthy subjects. The purpose of this study was to determine whether neutrophils from hanseniasis patients were altered in their enzyme systems myeloperoxidase-dependent (tested by lysin of Candida albicans) and myeloperoxidase-independent (tested by lysin of Candida pseudotropicalis). The results indicate that polymorphonuclear neutrophils of hanseniasis patients had a similar candidacidal activity that human normal neutrophils (p greater than 0.2) in their myeloperoxidase-dependent and myeloperoxidase-independent systems. The enzymatic system activity is also similar in all clinical forms of hanseniasis (p greater than 0.3).

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

    Directory of Open Access Journals (Sweden)

    Read Pukkila-Worley

    2011-06-01

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

  10. Prevalencia de Candida albicans y Candida no albicans en diferentes muestras clínicas: Período 1999-2001 Prevalence of Candida albicansand Candida no albicans inclinical samples during 1999-2001

    Directory of Open Access Journals (Sweden)

    M.T. Mujica

    2004-09-01

    Full Text Available Las levaduras implicadas en procesos patológicos son de indiscutible importancia debido al incremento experimentado por estas infecciones en las últimas décadas, a los cambios observados en las especies causales y al uso empírico de antifúngicos. En el Centro de Micología se estudiaron 1006 aislamientos provenientes de una amplia gama de muestras clínicas durante el periodo 1999-2001. Candida albicans con 40,3% resultó la especie de mayor frecuencia de aislamiento, pero las especies de Candida no albicans con 54,9% resultaron de mayor prevalencia y el 4,8% fueron otras levaduras. En los hemocultivos Candida parapsilosis con 34,9%, C. albicans con 30,2% y C. tropicalis con 25,6% resultaron las más recuperadas, mientras que C. glabrata se presentó con un 2,3%. En las secreciones mucosas C.albicans con 60%-80% fue la especie preponderante. Hemos detectado especies de Candida causantes de mediastinitis, lo que nos alerta sobre su importancia en estos procesos. Las infecciones del tracto urinario por levaduras se detectaron en mayor frecuencia en individuos hospitalizados, resultando C. albicans con 47,7% la especie más aislada, y dentro de Candida no albicans, C. glabrata con 24,8% y C. tropicalis con 20,0%. En las onixis candidiásicas C. parapsilosis con 37,7% desplazó a C.albicans con 22,0% de este lugar anatómico. Los estudios de sensiblidad al fluconazol de las especies de Candida nos permiten concluir que C.albicans es una especie sensible y que los mayores porcentajes de resistencia se observaron en C. glabrata (21,41% y and C. krusei (69,23%.The importance of epidemiological monitoring of yeasts involved in pathologic processes is unquestionable due to the increase of these infections over the last decade, the changes observed in species causing candidiasis, and empirical antifungal treatment. At the Mycology Center, 1006 isolates from a wide range of clinical samples were studied during 1999-2001. Candida albicans (40.3% was

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

    Directory of Open Access Journals (Sweden)

    Eric F. Kong

    2016-10-01

    Full Text Available 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.

  12. 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.

  13. Antifungal activity of Morinda citrifolia fruit extract against Candida albicans.

    Science.gov (United States)

    Jainkittivong, Aree; Butsarakamruha, Tassanee; Langlais, Robert P

    2009-09-01

    The objective of the study was to investigate the antifungal activity of Morinda citrifolia fruit extract on Candida albicans. Juice extract from M. citrifolia fruit was lyophilized and used in antifungal testing. Antifungal activity of M. citrifolia fruit extract against C. albicans was tested in vitro at various concentrations and for different contact times. The inhibitory effect of M. citrifolia extract on C. albicans was determined by cultures and an applied broth dilution test. Using cultures, growth of C. albicans was not detected with 50 mg/mL of extract at 30-minute contact time or with 60 mg/mL of extract at 15-minute contact time. By the broth dilution test, the minimum fungicidal concentration of extract against C. albicans was 40 mg/mL at 90-minute contact time or with 50 mg/mL at 15-minute contact time. M. citrifolia fruit extract had an antifungal effect on C. albicans and the inhibitory effect varied with concentration and contact time.

  14. 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.

  15. 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.

  16. 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.

  17. Application of the systematic “DAmP” approach to create a partially defective C. albicans mutant

    OpenAIRE

    Finkel, JS; Yudanin, N; Nett, JE; Andes, DR; Mitchell, AP

    2011-01-01

    An understanding of gene function often relies upon creating multiple kinds of alleles. Functional analysis in Candida albicans, a major fungal pathogen, has generally included characterization of mutant strains with insertion or deletion alleles and over-expression alleles. Here we use in C. albicans another type of allele that has been employed effectively in the model yeast Saccharomyces cerevisiae, a “Decreased Abundance by mRNA Perturbation” (DAmP) allele (Yan et al., 2008). DAmP alleles...

  18. Liquid and vapour-phase antifungal activities of essential oils against Candida albicans and non-albicans Candida.

    Science.gov (United States)

    Mandras, Narcisa; Nostro, Antonia; Roana, Janira; Scalas, Daniela; Banche, Giuliana; Ghisetti, Valeria; Del Re, Simonetta; Fucale, Giacomo; Cuffini, Anna Maria; Tullio, Vivian

    2016-08-30

    The management of Candida infections faces many problems, such as a limited number of antifungal drugs, toxicity, resistance of Candida to commonly antifungal drugs, relapse of Candida infections, and the high cost of antifungal drugs. Though azole antifungal agents and derivatives continue to dominate as drugs of choice against Candida infections, there are many available data referring to the anticandidal activity of essential oils. Since we have previous observed a good antimicrobial activity of some essential oils against filamentous fungi, the aim of this study was to extend the research to evaluate the activity of the same oils on Candida albicans, C.glabrata and C.tropicalis clinical strains, as well as the effects of related components. Essential oils selection was based both on ethnomedicinal use and on proved antibacterial and/or antifungal activity of some of these oils. Fluconazole and voriconazole were used as reference drugs. The minimum inhibitory concentration (MIC) and the minimal fungicidal concentration (MFC) of essential oils (thyme red, fennel, clove, pine, sage, lemon balm, and lavender) and their major components were investigated by the broth microdilution method (BM) and the vapour contact assay (VC). Using BM, pine oil showed the best activity against all strains tested, though C.albicans was more susceptible than C.glabrata and C.tropicalis (MIC50-MIC90 = 0.06 %, v/v). On the contrary, sage oil displayed a weak activity (MIC50-MIC90 = 1 %, v/v). Thyme red oil (MIC50-MIC90 ≤ 0.0038 %, v/v for C.albicans and C.tropicalis, and 0.0078- Candida spp., including fluconazole/voriconazole resistant strains. These data encourage adequately controlled and randomized clinical investigations. The use in vapour phase could have additional advantages without requiring direct contact, resulting in easy of environmental application such as in hospital, and/or in school.

  19. Invasive candidiasis in intensive care units in China: Risk factors and prognoses of Candida albicans and non-albicans Candida infections.

    Science.gov (United States)

    Gong, Xiaoying; Luan, Ting; Wu, Xingmao; Li, Guofu; Qiu, Haibo; Kang, Yan; Qin, Bingyu; Fang, Qiang; Cui, Wei; Qin, Yingzhi; Li, Jianguo; Zang, Bin

    2016-05-01

    To investigate the risk factors and prognoses of patients with invasive Candida albicans and non-albicans Candida (NAC) infection in intensive care units (ICUs) in China. Between November 2009 and April 2011, we performed a prospective study of critically ill patients with invasive Candida infection from 67 ICUs across China to compare the risk factors and mortality between patients with C albicans and NAC infection. There were 306 patients with proven invasive Candida; 244 cases (a total 389 Candida isolates) were sent to laboratory for strain identification (C albicans, 40.1%; NAC, 59.9%). More patients admitted for surgery or trauma had NAC infection than C albicans infection. C albicans infection was more common in patients with subclavian vein catheters or peritoneal drainage tubes. Compared with patients with C albicans infection, patients with NAC infection had longer antifungal therapy (P albicans remains the most common pathogen in candidiasis in critical care patients. However, the number of NAC infections exceeded C albicans infections. Compared with patients with C albicans infection, patients with NAC infection had heavier disease burdens. Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

  20. SILAC Expands its Territory to the Pathogenic Yeast, Candida albicans.

    Science.gov (United States)

    Jang, Wooyoung Eric; Kim, Min-Sik

    2018-02-13

    Quantitative proteomic analysis using SILAC, as metabolic labeling with mass spectrometry (MS), has been used as an excellent technique to measure relative abundance change in proteins and post-transitional modifications. Since its development in 2002, SILAC has proven to have unique and specific advantage compared to other labeling methods such as iTRAQ and TMT. However, SILAC has limitations in its application to human tissue/organ samples and some types of unicellular organisms that convert supplemented heavy amino acids to others. In this issue, Kaneva et al.1 introduces a new application of SILAC to a pathogen, which allows quantitative proteomics analysis to be performed without the need of arginine auxotrophs for SILAC experiment. In fungal pathogens, such as Candida albicans and other yeast family, arginine metabolism is one of the factors that helps pathogen escape host's defenses. This prevents arginine auxotrophs from being used in Candida albicans research and limits SILAC-based MS method as a choice of quantitation. However, possibilities for quantitative proteomic analysis of a pathogenic yeast Candida albicans using SILAC has now opened by Kaneva et al.1 This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  1. 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.

  2. Genome-wide transposon mutagenesis in Saccharomyces cerevisiae and Candida albicans.

    Science.gov (United States)

    Xu, Tao; Bharucha, Nikë; Kumar, Anuj

    2011-01-01

    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.

  3. 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.

    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.

  4. 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.

  5. Antifungal activity of extracts and isolated compounds from Buchenavia tomentosa on Candida albicans and non-albicans.

    Science.gov (United States)

    Teodoro, Guilherme R; Brighenti, Fernanda L; Delbem, Alberto C Botazzo; Delbem, Ádina Cléia B; Khouri, Sonia; Gontijo, Aline Vidal L; Pascoal, Aislan Crf; Salvador, Marcos J; Koga-Ito, Cristiane Y

    2015-01-01

    This study aimed to evaluate the antifungal activity of Buchenavia tomentosa extract and bioactive compounds on six Candida species. The antimicrobial activity of extract was evaluated using standard strains and clinical isolates. Cytotoxicity was tested in order to evaluate cell damage caused by the extract. Extract was chemically characterized and the antifungal activity of its compounds was evaluated. Extract showed antifungal activity on Candida species. Candida non-albicans were more susceptible than Candida albicans. Low cytotoxicity for extract was observed. The isolated compounds presented antifungal activity at least against one Candida spp. and all compounds presented antifungal effect on Candida glabrata. Extracts from Buchenavia tomentosa showed promising antifungal activity on Candida species with low cytotoxicity. Gallic acid, corilagin and ellagic acid showed promising inhibitory activity on Candida glabrata.

  6. A role for Candida albicans superoxide dismutase enzymes in glucose signaling.

    Science.gov (United States)

    Broxton, Chynna N; He, Bixi; Bruno, Vincent M; Culotta, Valeria C

    2018-01-01

    The Saccharomyces cerevisiae and Candida albicans yeasts have evolved to differentially use glucose for fermentation versus respiration. S. cerevisiae is Crabtree positive, where glucose represses respiration and promotes fermentation, while the opportunistic fungal pathogen C. albicans is Crabtree negative and does not repress respiration with glucose. We have previously shown that glucose control in S. cerevisiae involves the antioxidant enzyme Cu/Zn superoxide dismutase (SOD1), where H 2 O 2 generated by SOD1 stabilizes the casein kinase YCK1 for glucose sensing. We now demonstrate that C. albicans SODs also participate in glucose regulation. C. albicans expresses two cytosolic SODs, Cu/Zn SOD1 and Mn containing SOD3, and both complemented a S. cerevisiae sod1Δ mutant in stabilizing YCK1. Moreover, in C. albicans cells, both SODs functioned to repress glucose transporter genes in response to glucose. However, the action of SODs in glucose control has diverged in the two yeasts. In S. cerevisiae, SOD1 specifically functions in the glucose sensing pathway involving YCK1 and the RGT1 repressor, but the analogous YCK/RGT1 pathway in C. albicans shows no control by SOD enzymes. Instead C. albicans SODs work in the glucose repression pathway involving the MIG1 transcriptional repressor. In C. albicans, the SODs repress glucose uptake, while in S. cerevisiae, SOD1 activates glucose uptake, in accordance with the divergent modes for glucose utilization in these two distantly related yeasts. Copyright © 2017 Elsevier Inc. All rights reserved.

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

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

    2015-01-01

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

  8. Nicotine Enhances Interspecies Relationship between Streptococcus mutans and Candida albicans

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    Shiyu Liu

    2017-01-01

    Full Text Available Streptococcus mutans and Candida albicans are common microorganisms in the human oral cavity. The synergistic relationship between these two species has been deeply explored in many studies. In the present study, the effect of alkaloid nicotine on the interspecies between S. mutans and C. albicans is explored. We developed a dual-species biofilm model and studied biofilm biomass, biofilm structure, synthesis of extracellular polysaccharides (EPS, and expression of glucosyltransferases (Gtfs. Biofilm formation and bacterial and fungal cell numbers in dual-species biofilms increased in the presence of nicotine. More C. albicans cells were present in the dual-species biofilms in the nicotine-treated groups as determined by scanning electron microscopy. The synthesis of EPS was increased by 1 mg/ml of nicotine as detected by confocal laser scanning microscopy. The result of qRT-PCR showed gtfs expression was upregulated when 1 mg/ml of nicotine was used. We speculate that nicotine promoted the growth of S. mutans, and more S. mutans cells attracted more C. albicans cells due to the interaction between two species. Since S. mutans and C. albicans are putative pathogens for dental caries, the enhancement of the synergistic relationship by nicotine may contribute to caries development in smokers.

  9. Nicotine Enhances Interspecies Relationship between Streptococcus mutans and Candida albicans.

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    Liu, Shiyu; Qiu, Wei; Zhang, Keke; Zhou, Xuedong; Ren, Biao; He, Jinzhi; Xu, Xin; Cheng, Lei; Li, Mingyun

    2017-01-01

    Streptococcus mutans and Candida albicans are common microorganisms in the human oral cavity. The synergistic relationship between these two species has been deeply explored in many studies. In the present study, the effect of alkaloid nicotine on the interspecies between S. mutans and C. albicans is explored. We developed a dual-species biofilm model and studied biofilm biomass, biofilm structure, synthesis of extracellular polysaccharides (EPS), and expression of glucosyltransferases (Gtfs). Biofilm formation and bacterial and fungal cell numbers in dual-species biofilms increased in the presence of nicotine. More C. albicans cells were present in the dual-species biofilms in the nicotine-treated groups as determined by scanning electron microscopy. The synthesis of EPS was increased by 1 mg/ml of nicotine as detected by confocal laser scanning microscopy. The result of qRT-PCR showed gtfs expression was upregulated when 1 mg/ml of nicotine was used. We speculate that nicotine promoted the growth of S. mutans, and more S. mutans cells attracted more C. albicans cells due to the interaction between two species. Since S. mutans and C. albicans are putative pathogens for dental caries, the enhancement of the synergistic relationship by nicotine may contribute to caries development in smokers.

  10. The identification of surface interaction of apotransferrin with Candida albicans.

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    Han, Yongmoon

    2014-10-01

    Our recent data indicate that apotransferrin, an iron-chelating protein, has anti-candidal activity by binding to the Candida albicans surface rather than just simple iron-chelation. Following that study, in this present study, we investigated the nature of the candidal surface substance that is responsible for the anticandidal activity by using (59)Fe(3+)-apotransferrin and biological assay methods. Data resulting from the binding studies showed that the yeast cells had one class of binding sites as analyzed by the Scatchard equation, and the binding was specific as determined by competitive binding assay with unlabeled and labeled transferrin. All these observations indicate that there is a substance(s) that mediates the binding. Thus, a mannoprotein-like substance was extracted from C. albicans surface using hot water-treatment. Radioisotope binding study revealed that the substance blocked the transferrin binding. At 25 μg of IHS (inhibitory substance) addition, there was 65 % inhibition of the transferrin binding to C. albicans (5 × 10(7) cells/ml) (P albicans interacts directly with iron-saturated transferrin (100 %). Thus, it was concluded that a candidate for transferrin receptor is involved in the anticandidal activity of transferrin when in direct contact with C. albicans.

  11. Adherence of Candida albicans to bladder mucosa: development and application of a tissue explant assay.

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    Lyman, C A; Navarro, E; Garrett, K F; Roberts, D D; Pizzo, P A; Walsh, T J

    1999-01-01

    In order to study the interactions between Candida species and uroepithelial tissue, a tissue explant assay was developed using bladder mucosa harvested from New Zealand white rabbits. Blastoconidia of Candida albicans, Candida tropicalis and Candida glabrata attached to the uroepithelial tissue in similar quantities. However, there was significantly more adherence to the uroepithelium by pre-germinated C. albicans compared with C. albicans blastoconidia. Furthermore, the amount of uroepithelial tissue injury was directly related to the length of exposure of the tissue to Candida. Thus, this tissue explant assay may provide a useful method for investigating properties related to fungal adherence to transitional uroepithelium and organism-mediated tissue injury.

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

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    Aurélie Crabbé

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

  13. 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

  14. Identification of small molecules that disrupt vacuolar function in the pathogen Candida albicans.

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    Helene Tournu

    Full Text Available The fungal vacuole is a large acidified organelle that performs a variety of cellular functions. At least a sub-set of these functions are crucial for pathogenic species of fungi, such as Candida albicans, to survive within and invade mammalian tissue as mutants with severe defects in vacuolar biogenesis are avirulent. We therefore sought to identify chemical probes that disrupt the normal function and/or integrity of the fungal vacuole to provide tools for the functional analysis of this organelle as well as potential experimental therapeutics. A convenient indicator of vacuolar integrity based upon the intracellular accumulation of an endogenously produced pigment was adapted to identify Vacuole Disrupting chemical Agents (VDAs. Several chemical libraries were screened and a set of 29 compounds demonstrated to reproducibly cause loss of pigmentation, including 9 azole antifungals, a statin and 3 NSAIDs. Quantitative analysis of vacuolar morphology revealed that (excluding the azoles a sub-set of 14 VDAs significantly alter vacuolar number, size and/or shape. Many C. albicans mutants with impaired vacuolar function are deficient in the formation of hyphal elements, a process essential for its pathogenicity. Accordingly, all 14 VDAs negatively impact C. albicans hyphal morphogenesis. Fungal selectivity was observed for approximately half of the VDA compounds identified, since they did not alter the morphology of the equivalent mammalian organelle, the lysosome. Collectively, these compounds comprise of a new collection of chemical probes that directly or indirectly perturb normal vacuolar function in C. albicans.

  15. The antifungal plant defensin HsAFP1 from Heuchera sanguinea induces apoptosis in Candida albicans

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    An M. Aerts

    2011-03-01

    Full Text Available Plant defensins are active against plant and human pathogenic fungi (such as Candida albicans and baker’s yeast. However, they are nontoxic to human cells, providing a possible source for treatment of fungal infections. In this study, we characterized the mode of action of the antifungal plant defensin HsAFP1 from coral bells by screening the Saccharomyces cerevisiae deletion mutant library for mutants with altered HsAFP1 sensitivity and verified the obtained genetic data by biochemical assays in S. cerevisiae and C. albicans. We identified 84 genes, which when deleted conferred at least 4-fold hypersensitivity or resistance to HsAFP1. A considerable part of these genes were found to be implicated in mitochondrial functionality. In line, sodium azide, which blocks the respiratory electron transport chain, antagonized HsAFP1 antifungal activity, suggesting that a functional respiratory chain is indispensable for HsAFP1 antifungal action. Since mitochondria are the main source of cellular reactive oxygen species (ROS, we investigated the ROS-inducing nature of HsAFP1. We showed that HsAFP1 treatment of C. albicans resulted in ROS accumulation. As ROS accumulation is one of the phenotypic markers of apoptosis in yeast, we could further demonstrate that HsAFP1 induced apoptosis in C. albicans. These data provide novel mechanistic insights in the mode of action of a plant defensin.

  16. Protective roles of mitochondrial manganese-containing superoxide dismutase against various stresses in Candida albicans.

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    Hwang, Cheol-Sang; Baek, Yong-Un; Yim, Hyung-Soon; Kang, Sa-Ouk

    2003-08-01

    Candida albicans contains copper- and zinc-containing superoxide dismutase but also two manganese-containing superoxide dismutases (MnSODs), one in the cytosol and the other in the mitochondria. Among these, the SOD2 gene encoding mitochondrial MnSOD was disrupted and overexpressed to investigate its roles in C. albicans. The null mutant lacking mitochondrial MnSOD was more sensitive than wild-type cells to various stresses, such as redox-cycling agents, heating, ethanol, high concentration of sodium or potassium and 99.9% O2. Interestingly, the sod2/sod2 mutant was rather more resistant to lithium and diamide than the wild-type, whereas overexpression of SOD2 increased susceptibility of C. albicans to these compounds. The inverse effect of mitochondrial MnSOD on lithium toxicity was relieved when the sod2/sod2 and SOD2-overexpressing cells were grown on the synthetic dextrose medium containing sulphur compounds such as methionine, cysteine, glutathione or sulphite, indicating that mitochondrial MnSOD may affect lithium toxicity through sulphur metabolism. Moreover, disruption or overexpression of SOD2 increased or decreased glutathione reductase activity and cyanide-resistant respiration by alternative oxidase, respectively. Taken together, these findings suggest that mitochondrial MnSOD is important for stress responses, lithium toxicity and cyanide-resistant respiration of C. albicans. Copyright 2003 John Wiley & Sons, Ltd.

  17. Identification of small molecules that disrupt vacuolar function in the pathogen Candida albicans.

    Science.gov (United States)

    Tournu, Helene; Carroll, Jennifer; Latimer, Brian; Dragoi, Ana-Maria; Dykes, Samantha; Cardelli, James; Peters, Tracy L; Eberle, Karen E; Palmer, Glen E

    2017-01-01

    The fungal vacuole is a large acidified organelle that performs a variety of cellular functions. At least a sub-set of these functions are crucial for pathogenic species of fungi, such as Candida albicans, to survive within and invade mammalian tissue as mutants with severe defects in vacuolar biogenesis are avirulent. We therefore sought to identify chemical probes that disrupt the normal function and/or integrity of the fungal vacuole to provide tools for the functional analysis of this organelle as well as potential experimental therapeutics. A convenient indicator of vacuolar integrity based upon the intracellular accumulation of an endogenously produced pigment was adapted to identify Vacuole Disrupting chemical Agents (VDAs). Several chemical libraries were screened and a set of 29 compounds demonstrated to reproducibly cause loss of pigmentation, including 9 azole antifungals, a statin and 3 NSAIDs. Quantitative analysis of vacuolar morphology revealed that (excluding the azoles) a sub-set of 14 VDAs significantly alter vacuolar number, size and/or shape. Many C. albicans mutants with impaired vacuolar function are deficient in the formation of hyphal elements, a process essential for its pathogenicity. Accordingly, all 14 VDAs negatively impact C. albicans hyphal morphogenesis. Fungal selectivity was observed for approximately half of the VDA compounds identified, since they did not alter the morphology of the equivalent mammalian organelle, the lysosome. Collectively, these compounds comprise of a new collection of chemical probes that directly or indirectly perturb normal vacuolar function in C. albicans.

  18. Polymicrobial biofilm formation by Candida albicans, Actinomyces naeslundii, and Streptococcus mutans is Candida albicans strain and medium dependent.

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    Arzmi, Mohd Hafiz; Alnuaimi, Ali D; Dashper, Stuart; Cirillo, Nicola; Reynolds, Eric C; McCullough, Michael

    2016-11-01

    Oral biofilms comprise of extracellular polysaccharides and polymicrobial microorganisms. The objective of this study was to determine the effect of polymicrobial interactions of Candida albicans, Actinomyces naeslundii, and Streptococcus mutans on biofilm formation with the hypotheses that biofilm biomass and metabolic activity are both C. albicans strain and growth medium dependent. To study monospecific biofilms, C. albicans, A. naeslundii, and S. mutans were inoculated into artificial saliva medium (ASM) and RPMI-1640 in separate vials, whereas to study polymicrobial biofilm formation, the inoculum containing microorganisms was prepared in the same vial prior inoculation into a 96-well plate followed by 72 hours incubation. Finally, biofilm biomass and metabolic activity were measured using crystal violet and XTT assays, respectively. Our results showed variability of monospecies and polymicrobial biofilm biomass between C. albicans strains and growth medium. Based on cut-offs, out of 32, seven RPMI-grown biofilms had high biofilm biomass (HBB), whereas, in ASM-grown biofilms, 14 out of 32 were HBB. Of the 32 biofilms grown in RPMI-1640, 21 were high metabolic activity (HMA), whereas in ASM, there was no biofilm had HMA. Significant differences were observed between ASM and RPMI-grown biofilms with respect to metabolic activity (P biofilm biomass and metabolic activity were both C. albicans strain and growth medium dependent. © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. Galleria mellonella lysozyme induces apoptotic changes in Candida albicans cells.

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    Sowa-Jasiłek, Aneta; Zdybicka-Barabas, Agnieszka; Stączek, Sylwia; Wydrych, Jerzy; Skrzypiec, Krzysztof; Mak, Paweł; Deryło, Kamil; Tchórzewski, Marek; Cytryńska, Małgorzata

    2016-12-01

    The greater wax moth Galleria mellonella has been increasingly used as a model host to determine Candida albicans virulence and efficacy of antifungal treatment. The G. mellonella lysozyme, similarly to its human counterpart, is a member of the c-type family of lysozymes that exhibits antibacterial and antifungal activity. However, in contrast to the relatively well explained bactericidal action, the mechanism of fungistatic and/or fungicidal activity of lysozymes is still not clear. In the present study we provide the direct evidences that the G. mellonella lysozyme binds to the protoplasts as well as to the intact C. albicans cells and decreases the survival rate of both these forms in a time-dependent manner. No enzymatic activity of the lysozyme towards typical chitinase and β-glucanase substrates was detected, indicating that hydrolysis of main fungal cell wall components is not responsible for anti-Candida activity of the lysozyme. On the other hand, pre-treatment of cells with tetraethylammonium, a potassium channel blocker, prevented them from the lysozyme action, suggesting that lysozyme acts by induction of programmed cell death. In fact, the C. albicans cells treated with the lysozyme exhibited typical apoptotic features, i.e. loss of mitochondrial membrane potential, phosphatidylserine exposure in the outer leaflet of the cell membrane, as well as chromatin condensation and DNA fragmentation. Copyright © 2016 Elsevier GmbH. All rights reserved.

  20. A human-curated annotation of the Candida albicans genome.

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    Burkhard R Braun

    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.

  1. 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.

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

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

    2012-01-01

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

  3. Elderly nutritional status effection salivary anticandidal capacity against Candida albicans

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    Ria Puspitawati

    2011-06-01

    Full Text Available Background: Elderly often suffer malnutrition and oral candidiasis. Candida albicans (C. albicans which is the most prominent cause of oral candidiasis, is one of commensal oral micro-flora. Nutritional status affect the characteristic of saliva. Saliva is the regulator in the development of C. albicans from comensal into pathogen. Purpose: The purpose of this study was to determining the correlation between elderly nutritional status with salivary total protein and its activity in inhibiting C. albicans growth and biofilm formation. Methods: Using mini nutritional assessment 30 elderly were classified into normal and malnutrition groups. Total protein of unstimulated saliva was measured using Bradford protein assay. The colony forming unit (CFU of C. albicans was counted on 72 hours on SDA cultures without (control or with 2 hour saliva exposure. Biofilm formation was analyzed from the optical density of 10–5 C. albicans suspension without saliva exposure (control or with exposure of 10.000 μg/ml saliva and incubated in 37° C for 2 days. The suspension was put into 96 well plates, stained with crystal-violet dye, and analyzed using microplate reader. Differences between groups were analyzed using independent t-test or Kruskall-Wallis. Correlation between variables was analyzed using Spearman test. Results: Salivary total protein of normal elderly (1.113.5 ± 1.1143.3 was higher than those of malnutrition (613.6 ± 253.6 but not statistically significant (p > 0.05. The CFU of C. albicans exposed to saliva of normal samples (2.060 cfu/ml was significantly lower than control (24.100 cfu/ml and those exposed to malnutrition saliva (5.513.3 cfu/ml. C. albicans biofilm formation is highest in controls (0.177, lower in those exposed to malnourished saliva (0.151 and lowest in those exposed to saliva of good nourished elderly (0.133. Conclusion: Although does not cause significant decrease of salivary total protein, malnutrition in elderly results

  4. Culture media profoundly affect Candida albicans and Candida tropicalis growth, adhesion and biofilm development.

    Science.gov (United States)

    Weerasekera, Manjula M; Wijesinghe, Gayan K; Jayarathna, Thilini A; Gunasekara, Chinthika P; Fernando, Neluka; Kottegoda, Nilwala; Samaranayake, Lakshman P

    2016-11-01

    As there are sparse data on the impact of growth media on the phenomenon of biofilm development for Candida we evaluated the efficacy of three culture media on growth, adhesion and biofilm formation of two pathogenic yeasts, Candida albicans and Candida tropicalis. The planktonic phase yeast growth, either as monocultures or mixed cultures, in sabouraud dextrose broth (SDB), yeast nitrogen base (YNB), and RPMI 1640 was compared, and adhesion as well as biofilm formation were monitored using MTT and crystal violet (CV) assays and scanning electron microscopy. Planktonic cells of C. albicans, C. tropicalis and their 1:1 co-culture showed maximal growth in SDB. C. albicans/C. tropicalis adhesion was significantly facilitated in RPMI 1640 although the YNB elicited the maximum growth for C. tropicalis. Similarly, the biofilm growth was uniformly higher for both species in RPMI 1640, and C. tropicalis was the slower biofilm former in all three media. Scanning electron microscopy images tended to confirm the results of MTT and CV assay. Taken together, our data indicate that researchers should pay heed to the choice of laboratory culture media when comparing relative planktonic/biofilm growth of Candida. There is also a need for standardisation of biofilm development media so as to facilitate cross comparisons between laboratories.

  5. Identification of the cell targets important for propolis-induced cell death in Candida albicans.

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    de Castro, Patrícia Alves; Bom, Vinícius Leite Pedro; Brown, Neil Andrew; de Almeida, Ricardo Sérgio Couto; Ramalho, Leandra Naira Zambelli; Savoldi, Marcela; Goldman, Maria Helena S; Berretta, Andresa A; Goldman, Gustavo Henrique

    2013-11-01

    Candida albicans is the most common fungal pathogen of humans, forming both commensal and opportunistic pathogenic interactions, causing a variety of skin and soft tissue infections in healthy people. In immunocompromised patients C. albicans can result in invasive, systemic infections that are associated with a high incidence of mortality. Propolis is a complex mixture of several resinous substances which are collected from plants by bees. Here, we demonstrated the fungicidal activity of propolis against all three morphogenetic types of C. albicans and that propolis-induced cell death was mediated via metacaspase and Ras signaling. To identify genes that were involved in propolis tolerance, we screened ~800 C. albicans homozygous deletion mutants for decreased tolerance to propolis. Fifty-one mutant strains were identified as being hypersensitive to propolis including seventeen genes involved in cell adhesion, biofilm formation, filamentous growth, phenotypic switching and pathogenesis (HST7, GIN4, VPS34, HOG1, ISW2, SUV3, MDS3, HDA2, KAR3, YHB1, NUP85, CDC10, MNN9, ACE2, FKH2, and SNF5). We validated these results by showing that propolis inhibited the transition from yeast-like to hyphal growth. Propolis was shown to contain compounds that conferred fluorescent properties to C. albicans cells. Moreover, we have shown that a topical pharmaceutical preparation, based upon propolis, was able to control C. albicans infections in a mouse model for vulvovaginal candidiasis. Our results strongly indicate that propolis could be used as a strategy for controlling candidiasis. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Rapid differentiation of Candida dubliniensis from Candida albicans by early D-xylose assimilation.

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    Ellepola, A N B; Khan, Z U

    2012-01-01

    To determine if D-xylose (XYL) and/or α-methyl-D-glucoside (MDG) assimilation can be used reliably as a rapid test to differentiate Candida dubliniensis from Candida albicans at an earlier time point such as 2 h after inoculation. Thirty isolates of C. albicans and C. dubliniensis recovered from anatomical sites and clinical specimens were used. Isolates were inoculated into the API 20C AUX yeast identification system, and incubated at 30°C. XYL and MDG assimilations were read at 2-hour intervals beginning 2 h after the initial inoculation and up to 24 h of incubation; thereafter, results were read after 48 and 72 h. Twenty-nine (97%) C. albicans isolates had assimilated XYL at 16 h and, by 24 h, all isolates were positive for XYL assimilation. None of the C. dubliniensis isolates assimilated XYL. The MDG assimilation revealed that 24, 40, 92 and 100% of C. albicans isolates became positive after 16, 24, 48 and 72 h of incubation, respectively, whereas only 3% of C. dubliniensis isolates assimilated MDG after 72 h. The findings showed that it is possible to rapidly differentiate C. albicans from C. dubliniensis isolates using the API 20C AUX carbohydrate assimilation kits after 16 h of incubation at 30°C based on the XYL assimilation. Copyright © 2012 S. Karger AG, Basel.

  7. Variation in biofilm formation among blood and oral isolates of Candida albicans and Candida dubliniensis.

    Science.gov (United States)

    Villar-Vidal, María; Marcos-Arias, Cristina; Eraso, Elena; Quindós, Guillermo

    2011-11-01

    Biofilm production is considered a potential virulence factor of some Candida species. For this reason, an understanding of biofilm behavior of Candida albicans and its closely related species Candida dubliniensis is key to the development of effective preventive measures for invasive and oral candidiasis. The aim of this study was to compare the capacity of biofilm production by blood and oral isolates of C. albicans and C. dubliniensis using polystyrene, flat-bottomed 100-well microtiter plates. A total of 47 isolates, consisting of 28 C. albicans (16 oral and 12 blood isolates) and 19 C. dubliniensis (11 oral and 8 blood isolates) were compared for their biofilm forming ability under aerobic and static conditions. XTT reduction assay was used to quantify the sessile growth. All tested isolates produced biofilm, measured as XTT metabolic activity. Biofilm formation by C. albicans isolates was statistically significantly higher than biofilm formation by C. dubliniensis isolates at 24h (P=0.03) and 48 h (P=0.0001). There was a higher percentage (41.7%) of high producers of biofilms among C. albicans blood isolates than among oral isolates (31.3%), without statistically significant differences. This capability may allow C. albicans and C. dubliniensis to maintain their oral ecological niches as commensal or pathogenic microorganisms and can be a major virulence factor during invasive candidiasis. However, the differences in biofilm production among isolates should be taken into account when the anti-biofilm activity of antifungal agents or other virulence factors are tested in vitro. Copyright © 2011 Elsevier España, S.L. All rights reserved.

  8. 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. © 2013 Blackwell Verlag GmbH.

  9. Cross-kingdom interactions: Candida albicans and bacteria.

    Science.gov (United States)

    Shirtliff, Mark E; Peters, Brian M; Jabra-Rizk, Mary Ann

    2009-10-01

    Bacteria and fungi are found together in a myriad of environments and particularly in a biofilm, where adherent species interact through diverse signaling mechanisms. Yet, despite billions of years of coexistence, the area of research exploring fungal-bacterial interactions, particularly within the context of polymicrobial infections, is still in its infancy. However, reports describing a multitude of wide-ranging interactions between the fungal pathogen Candida albicans and various bacterial pathogens are on the rise. An example of a mutually beneficial interaction is coaggregation, a phenomenon that takes place in oral biofilms where the adhesion of C. albicans to oral bacteria is considered crucial for its colonization of the oral cavity. In contrast, the interaction between C. albicans and Pseudomonas aeruginosa is described as being competitive and antagonistic in nature. Another intriguing interaction is that occurring between Staphylococcus aureus and C. albicans, which although not yet fully characterized, appears to be initially synergistic. These complex interactions between such diverse and important pathogens would have significant clinical implications if they occurred in an immunocompromised host. Therefore, understanding the mechanisms of adhesion and signaling involved in fungal-bacterial interactions may lead to the development of novel therapeutic strategies for impeding microbial colonization and development of polymicrobial disease. © 2009 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Fikadu G Tafesse

    2015-10-01

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

  11. Antimicrobial Activity of Five Medicinal Plants on Candida Albicans

    Directory of Open Access Journals (Sweden)

    Fatemeh Masomi

    2016-10-01

    Full Text Available Background: In recent years, drug resistance to human pathogenic fungi has been increased. Medicinal plants are one way to overcome antibiotic resistance. The aim of this study was to evaluate the antifungal and inhibitory activity of five medicinal plants on the growth of Candida albicans. Methods: This study was done in the Microbiology Lab of Shahid Bahonar University of Kerman, Iran in 2015. Five medicinal plants include: Trachyspermum ammi (seed, Teucrium polium (leaf, Piper nigrum (seed, Pistachia vera (skin, Camelia sinensis (leaf were collected. Collected plant materials were extracted by ethanol and methanol solvent with maceration method. Antifungal activity of the ethanolic and methanolic extracts was evaluated by paper disc diffusion and agar well diffusion methods. Besides, MIC and MBC of each extract was determined. Results: All plant extracts had sufficient inhibitory effect against C. albicans but the extracts of P. vera had the best inhibitory effect on C. albicans (ZOI: 40 mm. The lowest antifungal effect between these five plants related to Piper nigrum (ZOI: 13 mm. Besides, the P. vera extracts had the best MIC and MBC values (6.25 and 12.5 mg/ml. Conclusion: This study strongly evidence the maximum antimicrobial activity of medicinal plants against C. albicans that this inhibitory effect varies with the different solvent-extract form. A more comprehensive study need to identify the effective compounds that have these antifungal properties.

  12. Vitamin D3 a new drug against Candida albicans.

    Science.gov (United States)

    Bouzid, D; Merzouki, S; Bachiri, M; Ailane, S E; Zerroug, M M

    2017-03-01

    In this study, we demonstrate that vitamin D3 had fungicidal activity against Candida albicans. The susceptibility of the yeast strain to the vitamin D3 was investigated by the antimicrobial screening using modified agar diffusion method, minimum fungistatic concentrations (MFCs) and minimum fungicide concentrations (MFCC) of the vitamin D3 were determined by the broth dilution method. The antifungal activity indicted that 100μg/ml of vitamin D3 had a power inhibition in the growth of C. albicans with zone of inhibition 12.5mm and CMFC and CMFs were 1.58±0.0764μg/ml. These values indicate that vitamin D3 can be considered to have fungicide activity. This antifungal effect may be due to the large lipsolubility of vitamin D3 changing the integrity of the cell membrane. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  13. Effect of 5-aminolevulinic acid photodynamic therapy on Candida albicans biofilms: An in vitro study.

    Science.gov (United States)

    Shi, Hang; Li, Jiyang; Zhang, Hui; Zhang, Jie; Sun, Hongying

    2016-09-01

    In this study, the photoinactivation of 5-aminolevulinic acid (ALA) has been investigated on Candida albicans biofilms in vitro. After culture and proliferation of Candida albicans biofilms in vitro, the metabolic activity was confirmed using XTT reduction assay. Then, the suitable incubation time and concentration of ALA were determined by measuring PpIX accumulation quantities. Photosensitivity of the biofilms treated with ALA solution was studied in optical doses of 50, 100, 200 and 300J/cm(2) while light irradiation was applied by a red light semiconductor. Finally, rapid immunofluorescence staining method using the LIVE/DEAD FungaLight Yeast Viability Kit and XTT assay were conducted to visualize and quantify the antifungal effect of ALA-PDT on Candida albicans biofilms. A 5h incubation time and 15mM ALA concentration were determined for this study. Photoinactivation of ALA-PDT on Candida albicans biofilms showed a significant increase of protoporphyrin IX (PpIX) in the biofilms. The metabolic activity of Candida albicans biofilms tread with ALA-PDT confirmed the inhibition efficacy compared with control groups. Upon radiation at 300J/cm(2), cells in Candida albicans biofilms were 74.45% inhibited. PpIX can be absorbed in biofilm-grown Candida albicans in vitro and under appropriate parameters, photochemistry can be triggered by light in combination with ALA and inhibits Candida albicans biofilms effectively. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. The efficacy of crude extract of Aloe secundiflora on Candida Albicans

    African Journals Online (AJOL)

    In- vitro studies on the efficacy of crude extracts of Aloe secundiflora on Candida albicans was conducted. Five mature leaves of Aloe secundiflora were collected and the crude extract was prepared, then autoclaved. The extract was then tested on Candida albicans grown on solid media. The results from these studies ...

  15. Molecular mechanisms of action of herbal antifungal alkaloid berberine, in Candida albicans.

    Directory of Open Access Journals (Sweden)

    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.

  16. Lemongrass-Incorporated Tissue Conditioner Against Candida albicans Culture

    Science.gov (United States)

    Amornvit, Pokpong; Srithavaj, Theerathavaj

    2014-01-01

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

  17. POTENSI ANTIMIKROBIA KRIM EKSTRAK RANTING PATAH TULANG (Euphorbia tirucalli Linn. TERHADAP Propionibacterium acnes ATCC 11827 DAN Candida albicans ATCC 24433

    Directory of Open Access Journals (Sweden)

    Melina Scandinovita Setiorini

    2016-04-01

    extracts with cream for testing Candida albicans.The final results were 10% test extract had MIC to Propionibacterium acnes and 6% test extract had MIC in cream to Candida albicans. Keywords: Euphorbia tirucalli L., DMSO, Thymol, antimicrobial potency, cream (o/w, Propionibacterium acnes, Candida albicans

  18. Comparative phenotypic analysis of the major fungal pathogens Candida parapsilosis and Candida albicans.

    Directory of Open Access Journals (Sweden)

    Linda M Holland

    2014-09-01

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

  19. Comparative phenotypic analysis of the major fungal pathogens Candida parapsilosis and Candida albicans.

    Science.gov (United States)

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

    2014-09-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  1. Antimicrobial effects of Coleus amboinicus, Lour folium infusum towards Candida albicans and Streptococcus mutans

    Directory of Open Access Journals (Sweden)

    Devi Rianti

    2006-03-01

    Full Text Available A laboratory experimental study conducted on antimicrobial effects of Coleus amboinicus, Lour folium Infusum towards Candida albicans and Streptococcus mutans (S. mutans. Effective concentration of Coleus amboinicus, Lour to decrease the quantities Candida albicans and S. mutans colonies is expected to be found out in this study. This study was using Coleus Amboinicus, Lour folium infusum with 12.5%, 15%, 17.5%, 20%, and 22.5% concentrations. Sterilized aquadest used as a control. Candida albicans and S. mutans quantities was enumerated by counting the amount of Candida albicans and S. mutans growth in the Sabouraud ,s dextrose agar and Tryptone and yeast Agar media, using Colony Forming Unit per milliliter (CFU/ ml unit. Data analysis was using a One-Way ANOVA and LSD with 5% degree of significance. The result showed 22.5% concentration of CAL folium infusum was the most effective in decreasing the quantity Candida albicans and S. mutans colonies.

  2. [Study the inhibitory effects of three oral actinomyces on growth of oral Candida albicans in vitro].

    Science.gov (United States)

    Li, Duo; Xiao, Xiao-rong; Zhu, Zhu; Ren, Qian; Hu, Tao; Gong, Qi-mei; Zhou, Hong-mei

    2008-10-01

    The aim of this study was to investigate whether the three species of oral Actinomyces have inhibitory effects on the growth of oral Candida albicans in vitro. Straight o'clock method was used to observe the bacteriostasis circle. Reverse o'clock and mixed culture method were used to study the quantitative changes of Candida albicans colony respectively. (1) None of the groups had been viewed the bacteriostasis circle. (2) Compared with control groups, there was a significant decrease of Candida albicans colony on Actinomyces viscosus TPY soft agar (P Actinomyces naeslundii and Actinomyces odontolyticus TPY soft agar were both devoid of obvious Candida albicans colony (P Actinomyces viscosus) and the two latter groups (Actinomyces naeslundii and Actinomyces odontolyticus) showed a striking contrast (P 0.05). Oral Actinomyces viscosus, Actinomyces naeslundii and Actinomyces odontolyticus could inhibit the growth of Candida albicans in vitro. However, which of them contributed more to the inhibitory effects was still not affirmed.

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

    Science.gov (United States)

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

    2017-04-01

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

  4. Synergistic Effects and Mechanisms of Budesonide in Combination with Fluconazole against Resistant Candida albicans.

    Science.gov (United States)

    Li, Xiuyun; Yu, Cuixiang; Huang, Xin; Sun, Shujuan

    2016-01-01

    Candida albicans is an important opportunistic pathogen, causing both superficial mucosal infections and life-threatening systemic diseases in the clinic. The emergence of drug resistance in Candida albicans has become a noteworthy phenomenon due to the extensive use of antifungal agents and the development of biofilms. This study showed that budesonide potentiates the antifungal effect of fluconazole against fluconazole-resistant Candida albicans strains both in vitro and in vivo. In addition, our results demonstrated, for the first time, that the combination of fluconazole and budesonide can reverse the resistance of Candida albicans by inhibiting the function of drug transporters, reducing the formation of biofilms, promoting apoptosis and inhibiting the activity of extracellular phospholipases. This is the first study implicating the effects and mechanisms of budesonide against Candida albicans alone or in combination with fluconazole, which may ultimately lead to the identification of new potential antifungal targets.

  5. Actin and phosphoinositide recruitment to fully formed Candida albicans phagosomes in mouse macrophages

    NARCIS (Netherlands)

    Heinsbroek, Sigrid E. M.; Kamen, Lynn A.; Taylor, Philip R.; Brown, Gordon D.; Swanson, Joel; Gordon, Siamon

    2009-01-01

    Candida albicans is a dimorphic yeast that enters macrophages (Mphi) via the beta-glucan receptor dectin-1. Phagocytosis of C. albicans is characterized by actin polymerization, Syk kinase activation and rapid acquisition of phagolysosomal markers. In mice, C. albicans are able to resist the harsh

  6. A Versatile Overexpression Strategy in the Pathogenic Yeast Candida albicans: Identification of Regulators of Morphogenesis and Fitness

    Science.gov (United States)

    Cabral, Vitor; Znaidi, Sadri; Goyard, Sophie; Bachellier-Bassi, Sophie; Firon, Arnaud; Legrand, Mélanie; Diogo, Dorothée; Naulleau, Claire; Rossignol, Tristan; d’Enfert, Christophe

    2012-01-01

    Candida albicans is the most frequently encountered human fungal pathogen, causing both superficial infections and life-threatening systemic diseases. Functional genomic studies performed in this organism have mainly used knock-out mutants and extensive collections of overexpression mutants are still lacking. Here, we report the development of a first generation C. albicans ORFeome, the improvement of overexpression systems and the construction of two new libraries of C. albicans strains overexpressing genes for components of signaling networks, in particular protein kinases, protein phosphatases and transcription factors. As a proof of concept, we screened these collections for genes whose overexpression impacts morphogenesis or growth rates in C. albicans. Our screens identified genes previously described for their role in these biological processes, demonstrating the functionality of our strategy, as well as genes that have not been previously associated to these processes. This article emphasizes the potential of systematic overexpression strategies to improve our knowledge of regulatory networks in C. albicans. The C. albicans plasmid and strain collections described here are available at the Fungal Genetics Stock Center. Their extension to a genome-wide scale will represent important resources for the C. albicans community. PMID:23049891

  7. Interaction Studies of Secreted Aspartic Proteases (Saps) from Candida albicans : Application for Drug Discovery

    OpenAIRE

    Backman, Dan

    2005-01-01

    This thesis is focused on enzymatic studies of the secreted aspartic proteases (Saps) from Candida albicans as a tool for discovery of anti-candida drugs. C. albicans causes infections in a number of different locations, which differ widely in the protein substrates available and pH. Since C. albicans needs Saps during virulent growth, these enzymes are good targets for drug development. In order to investigate the catalytic characteristics of Saps and their inhibitor affinities, substrate-ba...

  8. Spread of Throat and Genital Candida albicans Infections in Different Age Groups

    OpenAIRE

    , A Liti; , M. Hysko

    2016-01-01

    Candida albicans is an opportunistic human fungal pathogen. C. albicans is known to form two distinct types of filaments: pseudohyphae and hyphae. Yeast infections or thrush caused by Candida spp. and especially by C. albicans, are called Candidiasis. Candidiasis can be classified into two categories: in the first category are the mucosal infections which are characterized by white spots in the infected membranes and in the second one are the life-threatening infections. In this study we have...

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

    Directory of Open Access Journals (Sweden)

    Saif Hameed

    2011-04-01

    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

  10. Effects of fluconazole on the metabolomic profile of Candida albicans.

    Science.gov (United States)

    Katragkou, Aspasia; Alexander, Elizabeth L; Eoh, Hyungjin; Raheem, Saki K; Roilides, Emmanuel; Walsh, Thomas J

    2016-03-01

    Little is known about the effects of fluconazole on the metabolism of Candida albicans. We performed LC/MS-based metabolomic profiling of the response of C. albicans cells to increasing doses of fluconazole. C. albicans cells were cultured to mid-logarithmic growth phase in liquid medium and then inoculated in replicate on to nitrocellulose filters under vacuum filtration. Organisms were cultured to mid-logarithmic growth phase and treated with 0-4 mg/L fluconazole. Following metabolic quenching at mid-logarithmic growth phase, intracellular metabolites were extracted and analysed by LC/MS. Changes in pool sizes of individual metabolites were verified by Student's t-test, adjusted for multiple hypothesis testing by Benjamini-Hochberg correction. Distribution of metabolites was analysed by the Kyoto Encyclopedia of Genes and Genomes metabolic pathways database. We reproducibly detected 64 metabolites whose identities were confirmed by comparison against a pure standard and a library of accurate mass-retention time pairs. These 64 metabolites were broadly representative of eukaryotic central metabolic pathways. Among them 12 had their mean abundance significantly altered in response to increasing fluconazole concentrations. Pool sizes of four intermediates of central carbon metabolism (α-ketoglutarate, glucose-6-phosphate, phenylpyruvate and ribose-5-phosphate) and mevalonate were increased by 0.5-1.5-fold (P ≤ 0.05). Five amino acids (glycine, proline, tryptophan, aminoisobutanoate and asparagine) and guanine were decreased by 0.5-0.75-fold (P ≤ 0.05). Fluconazole treatment of C. albicans resulted in increased central carbon and decreased amino acid synthesis intermediates, suggesting a rerouting of metabolic pathways. The function of these metabolomic changes remains to be elucidated; however, they may represent previously unrecognized mechanisms of metabolic injury induced by fluconazole against C. albicans. © The Author 2015. Published by Oxford

  11. Distribution of Candida albicans and non-albicans Candida species in oral candidiasis patients: Correlation between cell surface hydrophobicity and biofilm forming activities.

    Science.gov (United States)

    Muadcheingka, Thaniya; Tantivitayakul, Pornpen

    2015-06-01

    The purposes of this investigation were to study the prevalence of Candida albicans and non-albicans Candida (NAC) species from oral candidiasis patients and evaluate the cell surface hydrophobicity (CSH) and biofilm forming capacity of the clinical isolates Candida species from oral cavity. This study identified a total of 250 Candida strains isolated from 207 oral candidiasis patients with PCR-RFLP technique. CSH value, total biomass of biofilm and biofilm forming ability of 117 oral Candida isolates were evaluated. C. albicans (61.6%) was still the predominant species in oral candidiasis patients with and without denture wearer, respectively, followed by C. glabrata (15.2%), C. tropicalis (10.4%), C. parapsilosis (3.2%), C. kefyr (3.6%), C. dubliniensis (2%), C. lusitaniae (2%), C. krusei (1.6%), and C. guilliermondii (0.4%). The proportion of mixed colonization with more than one Candida species was 18% from total cases. The relative CSH value and biofilm biomass of NAC species were greater than C. albicans (palbicans were biofilm formers. Furthermore, the significant difference of relative CSH values between biofilm formers and non-biofilm formers was observed in the NAC species (palbicans. The frequency of the NAC species colonization in oral cavity was gradually increasing. The possible contributing factors might be high cell surface hydrophobicity and biofilm forming ability. The relative CSH value could be a putative factor for determining biofilm formation ability of the non-albicans Candida species. Copyright © 2015 Elsevier Ltd. All rights reserved.

  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. Prevalence of Candida albicans and carriage of Candida non-albicans in the saliva of preschool children, according to their caries status.

    Science.gov (United States)

    Lozano Moraga, Carla Paola; Rodríguez Martínez, Gonzalo Andrés; Lefimil Puente, Claudia Andrea; Morales Bozo, Irene Cecilia; Urzúa Orellana, Blanca Regina

    2017-01-01

    This study was conducted to establish associations among the Candida carriage rate, the diversity of Candida species carried and the different caries status of preschool children. Sixty-one children between 2 and 5 years of age were examined by a single expert examiner and were divided into three groups, the caries-free, moderate caries and severe caries groups, according to the criteria of the International Caries Detection and Assessment System II (ICDAS). Saliva samples were obtained from the members of each group and were plated on Sabouraud agar plates to assess the Candida carriage rates. CHROMagar Candida medium was used for the preliminary screening. Biochemical testing or PCR/sequencing was conducted to identify the different Candida species in the samples. The differences observed were considered significant if the p value was Candida carriage rate and the number of species of this fungus carried were higher in the group with the highest level of caries severity (p Candida albicans was the most predominant Candida species in the saliva of all of the children, C. dubliniensis was identified only in the most caries-affected group in addition to other rare species of Candida non-albicans. A high salivary Candida carriage rate and the presence of specific species of this fungus (such as C. albicans and C. dubliniensis) appear to be related to the severity of caries experienced by preschool children.

  14. Candida albicans ISW2 Regulates Chlamydospore Suspensor Cell Formation and Virulence In Vivo in a Mouse Model of Disseminated Candidiasis

    Science.gov (United States)

    Lionakis, Michail S.; Nickerson, Kenneth W.

    2016-01-01

    Formation of chlamydospores by Candida albicans was an established medical diagnostic test to confirm candidiasis before the molecular era. However, the functional role and pathological relevance of this in vitro morphological transition to pathogenesis in vivo remain unclear. We compared the physical properties of in vitro-induced chlamydospores with those of large C. albicans cells purified by density gradient centrifugation from Candida-infected mouse kidneys. The morphological and physical properties of these cells in kidneys of mice infected intravenously with wild type C. albicans confirmed that chlamydospores can form in infected kidneys. A previously reported chlamydospore-null Δisw2/Δisw2 mutant was used to investigate its role in virulence and chlamydospore induction. Virulence of the Δisw2/Δisw2 mutant strain was reduced 3.4-fold compared to wild type C. albicans or the ISW2 reconstituted strain. Altered host inflammatory reactions to the null mutant further indicate that ISW2 is a virulence factor in C. albicans. ISW2 deletion abolished chlamydospore formation within infected mouse kidneys, whereas the reconstituted strain restored chlamydospore formation in kidneys. Under chlamydospore inducing conditions in vitro, deletion of ISW2 significantly delayed chlamydospore formation, and those late induced chlamydospores lacked associated suspensor cells while attaching laterally to hyphae via novel spore-hypha septa. Our findings establish the induction of chlamydospores by C. albicans during mouse kidney colonization. Our results indicate that ISW2 is not strictly required for chlamydospores formation but is necessary for suspensor cell formation. The importance of ISW2 in chlamydospore morphogenesis and virulence may lead to additional insights into morphological differentiation and pathogenesis of C. albicans in the host microenvironment. PMID:27727302

  15. Candida albicans menengitis in a newborn with classical galactosemia

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    Hüseyin Altunhan

    2012-12-01

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

  16. Chloroquine sensitizes biofilms of Candida albicans to antifungal azoles

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    Ravikumar Bapurao Shinde

    Full Text Available Biofilms formed by Candida albicans, a human pathogen, are known to be resistant to different antifungal agents. Novel strategies to combat the biofilm associated Candida infections like multiple drug therapy are being explored. In this study, potential of chloroquine to be a partner drug in combination with four antifungal agents, namely fluconazole, voriconazole, amphotericin B, and caspofungin, was explored against biofilms of C. albicans. Activity of various concentrations of chloroquine in combination with a particular antifungal drug was analyzed in a checkerboard format. Growth of biofilm in presence of drugs was analyzed by XTT-assay, in terms of relative metabolic activity compared to that of drug free control. Results obtained by XTT-metabolic assay were confirmed by scanning electron microscopy. The interactions between chloroquine and four antifungal drugs were determined by calculating fractional inhibitory concentration indices. Azole resistance in biofilms was reverted significantly (p < 0.05 in presence of 250 µg/mL of chloroquine, which resulted in inhibition of biofilms at very low concentrations of antifungal drugs. No significant alteration in the sensitivity of biofilms to caspofungin and amphotericin B was evident in combination with chloroquine. This study for the first time indicates that chloroquine potentiates anti-biofilm activity of fluconazole and voriconazole.

  17. Antimicrobial effects of liquid anesthetic isoflurane on Candida albicans

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    Armstead Valerie

    2006-11-01

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

  18. Transcription Factors Efg1 and Bcr1 Regulate Biofilm Formation and Virulence during Candida albicans-Associated Denture Stomatitis.

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    Junko Yano

    Full Text Available Denture stomatitis (DS is characterized by inflammation of the oral mucosa in direct contact with dentures and affects a significant number of otherwise healthy denture wearers. The disease is caused by Candida albicans, which readily colonizes and form biofilms on denture materials. While evidence for biofilms on abiotic and biotic surfaces initiating Candida infections is accumulating, a role for biofilms in DS remains unclear. Using an established model of DS in immunocompetent animals, the purpose of this study was to determine the role of biofilm formation in mucosal damage during pathogenesis using C. albicans or mutants defective in morphogenesis (efg1-/- or biofilm formation (bcr1-/-. For in vivo analyses, rats fitted with custom dentures, consisting of fixed and removable parts, were inoculated with wild-type C. albicans, mutants or reconstituted strains and monitored weekly for fungal burden (denture and palate, body weight and tissue damage (LDH for up to 8 weeks. C. albicans wild-type and reconstituted mutants formed biofilms on dentures and palatal tissues under in vitro, ex vivo and in vivo conditions as indicated by microscopy demonstrating robust biofilm architecture and extracellular matrix (ECM. In contrast, both efg1-/- and bcr1-/- mutants exhibited poor biofilm growth with little to no ECM. In addition, quantification of fungal burden showed reduced colonization throughout the infection period on dentures and palates of rats inoculated with efg1-/-, but not bcr1-/-, compared to controls. Finally, rats inoculated with efg1-/- and bcr1-/- mutants had minimal palatal tissue damage/weight loss while those inoculated with wild-type or reconstituted mutants showed evidence of tissue damage and exhibited stunted weight gain. These data suggest that biofilm formation is associated with tissue damage during DS and that Efg1 and Bcr1, both central regulators of virulence in C. albicans, have pivotal roles in pathogenesis of DS.

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

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    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.

  20. 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.

  1. Boric acid destabilizes the hyphal cytoskeleton and inhibits invasive growth of Candida albicans.

    Science.gov (United States)

    Pointer, Benjamin R; Boyer, Michael P; Schmidt, Martin

    2015-04-01

    Exposure of Candida albicans to sub-lethal concentrations of boric acid (BA) restricts the dimorphic fungus to its yeast morphology and prevents the formation of invasive hyphae on solid substrates. Exposure to BA causes a rapid and reversible disappearance of polarisome and Spitzenkörper in growing hyphae. In BA-treated hyphae of C. albicans, actin quickly reorganizes from cytoplasmic cables to cortical patches and cell wall growth switches from an apical to an isotropic pattern. As a result of the cytoskeletal changes, the hyphal tips broaden and directional growth of hyphae ceases in the presence of BA. An analysis of homozygous deletion strains showed that mutants with constitutive or enhanced hyphal growth (tup1, nrg1, ssn6, rbf1) are BA-sensitive, demonstrating that cellular morphology is a major determinant of BA tolerance. The screening of deletion mutants also showed that deficiencies of the main activator of hyphal gene expression, Efg1, and the Rim101-signalling cascade, leading to Efg1 activation, cause BA resistance. Taken together, the data presented show that the selective inhibitory effect on BA on C. albicans hyphae is rooted in a disruption of apical cytoskeletal elements of growing hyphae. Copyright © 2015 John Wiley & Sons, Ltd.

  2. The yeast form of the fungus Candida albicans promotes persistence in the gut of gnotobiotic mice.

    Science.gov (United States)

    Böhm, Lena; Torsin, Sanda; Tint, Su Hlaing; Eckstein, Marie Therese; Ludwig, Tobias; Pérez, J Christian

    2017-10-25

    Many microorganisms that cause systemic, life-threatening infections in humans reside as harmless commensals in our digestive tract. Yet little is known about the biology of these microbes in the gut. Here, we visualize the interface between the human commensal and pathogenic fungus Candida albicans and the intestine of mice, a surrogate host. Because the indigenous mouse microbiota restricts C. albicans settlement, we compared the patterns of colonization in the gut of germ free and antibiotic-treated conventionally raised mice. In contrast to the heterogeneous morphologies found in the latter, we establish that in germ free animals the fungus almost uniformly adopts the yeast cell form, a proxy of its commensal state. By screening a collection of C. albicans transcription regulator deletion mutants in gnotobiotic mice, we identify several genes previously unknown to contribute to in vivo fitness. We investigate three of these regulators-ZCF8, ZFU2 and TRY4-and show that indeed they favor the yeast form over other morphologies. Consistent with this finding, we demonstrate that genetically inducing non-yeast cell morphologies is detrimental to the fitness of C. albicans in the gut. Furthermore, the identified regulators promote adherence of the fungus to a surface covered with mucin and to mucus-producing intestinal epithelial cells. In agreement with this result, histology sections indicate that C. albicans dwells in the murine gut in close proximity to the mucus layer. Thus, our findings reveal a set of regulators that endows C. albicans with the ability to endure in the intestine through multiple mechanisms.

  3. Regulation of aromatic alcohol production in Candida albicans.

    Science.gov (United States)

    Ghosh, Suman; Kebaara, Bessie W; Atkin, Audrey L; Nickerson, Kenneth W

    2008-12-01

    Colonization by the fungal pathogen Candida albicans varies significantly, depending upon the pH and availability of oxygen. Because of our interest in extracellular molecules as potential quorum-sensing molecules, we examined the physiological conditions which regulate the production of the aromatic alcohols, i.e., phenethyl alcohol, tyrosol, and tryptophol. The production of these fusel oils has been well studied for Saccharomyces cerevisiae. Our data show that aromatic alcohol yields for C. albicans are determined by growth conditions. These conditions include the availability of aromatic amino acids, the pH, oxygen levels, and the presence of ammonium salts. For example, for wild-type C. albicans, tyrosol production varied 16-fold merely with the inclusion of tyrosine or ammonium salts in the growth medium. Aromatic alcohol production also depends on the transcription regulator Aro80p. Our results are consistent with aromatic alcohol production-aromatic transaminases (gene products for ARO8 and ARO9), aromatic decarboxylase (ARO10), and alcohol dehydrogenase (ADH)-via the fusel oil pathway. The expression of ARO8, ARO9, and ARO10 is also pH dependent. ARO8 and ARO9 were alkaline upregulated, while ARO10 was alkaline downregulated. The alkaline-dependent change in expression of ARO8 was Rim101 independent, while the expression of ARO9 was Rim101 dependent.

  4. 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. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. 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.

  6. 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

  7. Melanin externalization in Candida albicans depends on cell wall chitin structures.

    Science.gov (United States)

    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

    2010-09-01

    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 that were free or often loosely bound to the cell wall exterior. Melanin production was boosted by the addition of N-acetylglucosamine to the medium, indicating a possible association between melanin production and chitin synthesis. Melanin externalization was blocked in a mutant specifically disrupted in the chitin synthase-encoding gene CHS2. Melanosomes remained within the outermost cell wall layers in chs3Delta and chs2Delta chs3Delta mutants but were fully externalized in chs8Delta and chs2Delta chs8Delta mutants. All the CHS mutants synthesized dark pigment at equivalent rates from mixed membrane fractions in vitro, suggesting it was the form of chitin structure produced by the enzymes, not the enzymes themselves, that was involved in the melanin externalization process. Mutants with single and double disruptions of the chitinase genes CHT2 and CHT3 and the chitin pathway regulator ECM33 also showed impaired melanin externalization. We hypothesize that the chitin product of Chs3 forms a scaffold essential for normal externalization of melanosomes, while the Chs8 chitin product, probably produced in cell walls in greater quantity in the absence of CHS2, impedes externalization.

  8. Melanin Externalization in Candida albicans Depends on Cell Wall Chitin Structures▿

    Science.gov (United States)

    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 that were free or often loosely bound to the cell wall exterior. Melanin production was boosted by the addition of N-acetylglucosamine to the medium, indicating a possible association between melanin production and chitin synthesis. Melanin externalization was blocked in a mutant specifically disrupted in the chitin synthase-encoding gene CHS2. Melanosomes remained within the outermost cell wall layers in chs3Δ and chs2Δ chs3Δ mutants but were fully externalized in chs8Δ and chs2Δ chs8Δ mutants. All the CHS mutants synthesized dark pigment at equivalent rates from mixed membrane fractions in vitro, suggesting it was the form of chitin structure produced by the enzymes, not the enzymes themselves, that was involved in the melanin externalization process. Mutants with single and double disruptions of the chitinase genes CHT2 and CHT3 and the chitin pathway regulator ECM33 also showed impaired melanin externalization. We hypothesize that the chitin product of Chs3 forms a scaffold essential for normal externalization of melanosomes, while the Chs8 chitin product, probably produced in cell walls in greater quantity in the absence of CHS2, impedes externalization. PMID:20543065

  9. A family of glutathione peroxidases contributes to oxidative stress resistance in Candida albicans.

    Science.gov (United States)

    Miramón, Pedro; Dunker, Christine; Kasper, Lydia; Jacobsen, Ilse D; Barz, Dagmar; Kurzai, Oliver; Hube, Bernhard

    2014-04-01

    Candida albicans is a well-adapted human commensal but is also a facultative pathogen that can cause superficial and systemic infections. Its remarkable capacity to thrive within the human host relies on its ability to adapt and respond to the local environment of different niches. C. albicans is able to cope with oxidative stress in a coordinated fashion via upregulation of different protective mechanisms. Here, we unravel the role of a family of glutathione peroxidase (GPx), designated Gpx31, Gpx32, and Gpx33, in oxidative stress resistance. We show that GPx activity in C. albicans is induced upon exposure to peroxides and that this enzymatic activity is required for full resistance to oxidative stress. The GPx activity relies on the presence of GPX31, with no apparent contribution from GPX32 and GPX33 during in vitro short-term (3 h) exposure to peroxides. However, a triple gpx31-33Δ/Δ mutant exhibited a more pronounced sensitivity than a single gpx31Δ/Δ mutant on solid media in the presence of oxidants, suggesting that GPX32 and GPX33 may be involved in long-term adaptation to oxidative stress. Interestingly, reintegration of a single allele of GPX31 was sufficient to restore the wild-type phenotype in both the single and triple mutants. We found that mutants lacking GPX31-33 were more susceptible to killing by phagocytic cells, suggesting that GPxs are required for full resistance to innate immune effector cells. Despite the sensitivity to oxidative stress and phagocytes, these mutants were not affected in their virulence in the chicken embryo model of candidiasis.

  10. Coordination of Candida albicans Invasion and Infection Functions by Phosphoglycerol Phosphatase Rhr2

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    Jigar V. Desai

    2015-07-01

    Full Text Available The Candida albicans RHR2 gene, which specifies a glycerol biosynthetic enzyme, is required for biofilm formation in vitro and in vivo. Prior studies indicate that RHR2 is ultimately required for expression of adhesin genes, such as ALS1. In fact, RHR2 is unnecessary for biofilm formation when ALS1 is overexpressed from an RHR2-independent promoter. Here, we describe two additional biological processes that depend upon RHR2: invasion into an abiotic substrate and pathogenicity in an abdominal infection model. We report here that abiotic substrate invasion occurs concomitantly with biofilm formation, and a screen of transcription factor mutants indicates that biofilm and hyphal formation ability correlates with invasion ability. However, analysis presented here of the rhr2Δ/Δ mutant separates biofilm formation and invasion. We found that an rhr2Δ/Δ mutant forms a biofilm upon overexpression of the adhesin gene ALS1 or the transcription factor genes BRG1 or UME6. However, the biofilm-forming strains do not invade the substrate. These results indicate that RHR2 has an adhesin-independent role in substrate invasion, and mathematical modeling argues that RHR2 is required to generate turgor. Previous studies have shown that abdominal infection by C. albicans has two aspects: infection of abdominal organs and persistence in abscesses. We report here that an rhr2Δ/Δ mutant is defective in both of these infection phenotypes. We find here that overexpression of ALS1 in the mutant restores infection of organs, but does not improve persistence in abscesses. Therefore, RHR2 has an adhesin-independent role in abdominal infection, just as it does in substrate invasion. This report suggests that RHR2, through glycerol synthesis, coordinates adherence with host- or substrate-interaction activities that enable proliferation of the C. albicans population.

  11. Distinct roles of Candida albicans-specific genes in host-pathogen interactions.

    Science.gov (United States)

    Wilson, Duncan; Mayer, François L; Miramón, Pedro; Citiulo, Francesco; Slesiona, Silvia; Jacobsen, Ilse D; Hube, Bernhard

    2014-08-01

    Human fungal pathogens are distributed throughout their kingdom, suggesting that pathogenic potential evolved independently. Candida albicans is the most virulent member of the CUG clade of yeasts and a common cause of both superficial and invasive infections. We therefore hypothesized that C. albicans possesses distinct pathogenicity mechanisms. In silico genome subtraction and comparative transcriptional analysis identified a total of 65 C. albicans-specific genes (ASGs) expressed during infection. Phenotypic characterization of six ASG-null mutants demonstrated that these genes are dispensable for in vitro growth but play defined roles in host-pathogen interactions. Based on these analyses, we investigated two ASGs in greater detail. An orf19.6688Δ mutant was found to be fully virulent in a mouse model of disseminated candidiasis and to induce higher levels of the proinflammatory cytokine interleukin-1β (IL-1β) following incubation with murine macrophages. A pga16Δ mutant, on the other hand, exhibited attenuated virulence. Moreover, we provide evidence that secondary filamentation events (multiple hyphae emerging from a mother cell and hyphal branching) contribute to pathogenicity: PGA16 deletion did not influence primary hypha formation or extension following contact with epithelial cells; however, multiple hyphae and hyphal branching were strongly reduced. Significantly, these hyphae failed to damage host cells as effectively as the multiple hypha structures formed by wild-type C. albicans cells. Together, our data show that species-specific genes of a eukaryotic pathogen can play important roles in pathogenicity. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  12. Association of Oral Candida albicans with Severe Early Childhood Caries - A Pilot Study.

    Science.gov (United States)

    Thomas, Ann; Mhambrey, Sanjana; Chokshi, Krunal; Chokshi, Achala; Jana, Sinjana; Thakur, Sneha; Jose, Deepak; Bajpai, Garima

    2016-08-01

    In early childhood, children are more susceptible to opportunistic microbial colonization in the oral cavity due to immature immune system and not fully established micro flora. The current literature proposes a probable role of Candida albicans, a fungus in the etiopathogenesis of dental caries. This study was conducted to compare the Candida albicans count in children with severe early childhood caries and caries free children. A cross-sectional study was conducted in 40 randomly selected healthy children between 12 to 71 months of age, who were divided into two groups based on the caries experience as Severe Early Childhood Caries (SECC) (dmfs ≥4) and caries free (dmfs = 0). The caries experiences (dmfs index) of the 40 children were recorded using visible light and diagnostic instruments. A 2ml sample of unstimulated whole saliva collected from the children was transported to the microbiology laboratory in universal containers and evaluated for Candida albicans count using the selective media. The data was statistically analyzed using SPSS software 17.0. Candida albicans was found in both the SECC group and caries free group. Median Candida albicans of the SECC group was numerically greater than the caries free group and this difference was highly statistically significant (p=0.012). In this present cross-sectional study, we found a 100% prevalence of Candida albicans in the saliva of the study children. There was a highly significant increase in Candida albicans count in SECC children compared to the caries free children.

  13. Competitive Fitness of Fluconazole-Resistant Clinical Candida albicans Strains.

    Science.gov (United States)

    Popp, Christina; Hampe, Irene A I; Hertlein, Tobias; Ohlsen, Knut; Rogers, P David; Morschhäuser, Joachim

    2017-07-01

    The pathogenic yeast Candida albicans can develop resistance to the widely used antifungal agent fluconazole, which inhibits ergosterol biosynthesis. Resistance is often caused by gain-of-function mutations in the transcription factors Mrr1 and Tac1, which result in constitutive overexpression of multidrug efflux pumps, and Upc2, which result in constitutive overexpression of ergosterol biosynthesis genes. However, the deregulated gene expression that is caused by hyperactive forms of these transcription factors also reduces the fitness of the cells in the absence of the drug. To investigate whether fluconazole-resistant clinical C. albicans isolates have overcome the fitness costs of drug resistance, we assessed the relative fitness of C. albicans isolates containing resistance mutations in these transcription factors in competition with matched drug-susceptible isolates from the same patients. Most of the fluconazole-resistant isolates were outcompeted by the corresponding drug-susceptible isolates when grown in rich medium without fluconazole. On the other hand, some resistant isolates with gain-of-function mutations in MRR1 did not exhibit reduced fitness under these conditions. In a mouse model of disseminated candidiasis, three out of four tested fluconazole-resistant clinical isolates did not exhibit a significant fitness defect. However, all four fluconazole-resistant isolates were outcompeted by the matched susceptible isolates in a mouse model of gastrointestinal colonization, demonstrating that the effects of drug resistance on in vivo fitness depend on the host niche. Collectively, our results indicate that the fitness costs of drug resistance in C. albicans are not easily remediated, especially when proper control of gene expression is required for successful adaptation to life within a mammalian host. Copyright © 2017 American Society for Microbiology.

  14. [Epidemiology, risk factors and in vitro susceptibility in candidaemia due to non-Candida albicans species].

    Science.gov (United States)

    Marín Martínez, Elena M; Aller García, Ana Isabel; Martín-Mazuelos, Estrella

    Invasive fungal infection (IFI) has increased in recent years due to there being a greater number of risk factors. IFI caused by Candida is the most frequent, and although Candida albicans is the most isolated species, there is currently a decrease of C. albicans and an increase of other species of the genus. To analyse the epidemiology, risk factors, and antifungal susceptibility of blood culture isolates of non-C.albicans Candida species in our hospital in the last 12years. A retrospective study was conducted on 107 patients with candidaemia admitted to our hospital. Candida isolates susceptibility to fluconazole, itraconazole, voriconazole, amphotericinB, 5-fluorocytosine, caspofungin, micafungin, and anidulafungin was determined by means of a microdilution technique (Sensititre Yeast One; Izasa, Spain). From a total of 109 strains, 59 belonged to non-C. albicans Candida species: 25 Candida parapsilosis complex, 14 Candida glabrata complex, 13 Candida tropicalis, 4 Candida krusei, 1 Candida lipolytica, 1 Candida membranaefaciens, and 1 Candida pulcherrima. The most common risk factor in adults and children was catheter use. It was observed that 8.5% of those non-C.albicans strains were resistant to fluconazole. The results of this work confirm that it is necessary to know the epidemiology of non-C.albicans Candida species, the in vitro susceptibility of the species involved, and the main risk factors, especially in patients with predisposing conditions. Copyright © 2016 Asociación Española de Micología. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. 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.

  16. Antimicrobial effects of three tropical plant extracts on Staphylococcus aureus, Escherichia coli and Candida albicans.

    Science.gov (United States)

    Okigbo, R N; Mmeka, E C

    2008-04-10

    Antimicrobial activities of the leaf extracts of Cymbopogon citatrus (lemongrass) and Vernonia amygdalina (bitter leaf) and the seed extracts of Garcinia kola (bitter kola) were carried out. G. kola had effect only on Staphylococcus aureus and Escherichia coli with no inhibition on Candida albicans. Ethanol, cold water and hot water extracts of Vernonia amygdalina and Cymbopogon citratus showed inhibition on the three organism but G. kola ethanol, cold water and hot water extracts only inhibited S. aureus and E. coli with no inhibition on Candida albicans. The organism's susceptibility varied with more inhibition to S. aureus and least to Candida albicans.

  17. 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.

  18. Biophysical Effects of a Polymeric Biosurfactant in Candida krusei and Candida albicans Cells.

    Science.gov (United States)

    Ferreira, Gabriella Freitas; Dos Santos Pinto, Bruna Lorrana; Souza, Eliene Batista; Viana, José Lima; Zagmignan, Adrielle; Dos Santos, Julliana Ribeiro Alves; Santos, Áquila Rodrigues Costa; Tavares, Priscila Batista; Denadai, Ângelo Márcio Leite; Monteiro, Andrea Souza

    2016-12-01

    This study evaluated the effects of a polymeric biosurfactant produced by Trichosporon montevideense CLOA72 in the adhesion of Candida albicans and Candida krusei cells to human buccal epithelial cells and its interference in biofilm formation by these strains. The biofilm inhibition by biosurfactant (25 mg/mL) in C. krusei and C. albicans in polystyrene was reduced up to 79.5 and 85 %, respectively. In addition, the zeta potential and hydrodynamic diameter of the yeasts altered as a function of the biosurfactant concentration added to the cell suspension. The changes in the cell surface characteristics and the interface modification can contribute to the inhibition of the initial adherence of yeasts cells to the surface. In addition, the analyses of the biofilm matrix and planktonic cell surfaces demonstrated differences in carbohydrate and protein concentrations for the two studied strains, which may contribute to the modulation of cell adhesion or consolidation of biofilms, especially in C. krusei. This study suggests a possible application of the of CLOA72 biosurfactant in inhibiting the adhesion and formation of biofilms on biological surfaces by yeasts of the Candida genus.

  19. Candida albicans meningitis in an infant with noonan syndrome

    Directory of Open Access Journals (Sweden)

    Faezeh Ahmadi

    Full Text Available Noonan syndrome is a rare disorder, characterized by several malformations such as dysplasia and stenosis of the pulmonary valve, atrial septal defect and a typical pattern of hypertrophic cardiomyopathy. We describe here a 1-month old girl, who was referred to our center with seizure and apnea. She had wide anterior fontanel, head circumference and sunset eye. Intaventricular hemorrhage by sonography and atrial septal defect and hypertrophy cardiomyopathy by echocardiography were detected. Clinical and laboratory findings of the patient were compatible with a diagnosis of Noonan syndrome, which was also confirmed by molecular analysis. Candida albicans was grown in the blood and cerebrospinal fluid cultures. Treatment with Amphotrycine B was started for the patient and she responded well to this therapy. Early diagnosis and appropriate diagnosis of a rare condition in the patient with such rare disease are the main keys to avoid further complications and even death of patient.

  20. 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.

  1. Identification of a cell death pathway in Candida albicans during the response to pheromone.

    Science.gov (United States)

    Alby, Kevin; Schaefer, Dana; Sherwood, Racquel Kim; Jones, Stephen K; Bennett, Richard J

    2010-11-01

    Mating in hemiascomycete yeasts involves the secretion of pheromones that induce sexual differentiation in cells of the opposite mating type. Studies in Saccharomyces cerevisiae have revealed that a subpopulation of cells experiences cell death during exposure to pheromone. In this work, we tested whether the phenomenon of pheromone-induced death (PID) also occurs in the opportunistic pathogen Candida albicans. Mating in C. albicans is uniquely regulated by white-opaque phenotypic switching; both cell types respond to pheromone, but only opaque cells undergo the morphological transition and cell conjugation. We show that approximately 20% of opaque cells, but not white cells, of laboratory strain SC5314 experience pheromone-induced death. Furthermore, analysis of mutant strains revealed that PID was significantly reduced in strains lacking Fig1 or Fus1 transmembrane proteins that are induced during the mating process and, we now show, are necessary for efficient mating in C. albicans. The level of PID was also Ca(2+) dependent, as chelation of Ca(2+) ions increased cell death to almost 50% of the population. However, in contrast to S. cerevisiae PID, pheromone-induced killing of C. albicans cells was largely independent of signaling via the Ca(2+)-dependent protein phosphatase calcineurin, even when combined with the loss of Cmk1 and Cmk2 proteins. Finally, we demonstrate that levels of PID vary widely between clinical isolates of C. albicans, with some strains experiencing close to 70% cell death. We discuss these findings in light of the role of prodeath and prosurvival pathways operating in yeast cells undergoing the morphological response to pheromone.

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

    Science.gov (United States)

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

    2017-09-01

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

  3. Pharmacoeconomic analysis of antifungal therapy for primary treatment of invasive candidiasis caused by Candida albicans and non-albicans Candida species.

    Science.gov (United States)

    Ou, Huang-Tz; Lee, Tsung-Ying; Chen, Yee-Chun; Charbonneau, Claudie

    2017-07-10

    Cost-effectiveness studies of echinocandins for the treatment of invasive candidiasis, including candidemia, are rare in Asia. No study has determined whether echinocandins are cost-effective for both Candida albicans and non-albicans Candida species. There have been no economic evaluations that compare non-echinocandins with the three available echinocandins. This study was aimed to assess the cost-effectiveness of individual echinocandins, namely caspofungin, micafungin, and anidulafungin, versus non-echinocandins for C. albicans and non-albicans Candida species, respectively. A decision tree model was constructed to assess the cost-effectiveness of echinocandins and non-echinocandins for invasive candidiasis. The probability of treatment success, mortality rate, and adverse drug events were extracted from published clinical trials. The cost variables (i.e., drug acquisition) were based on Taiwan's healthcare system from the perspective of a medical payer. One-way sensitivity analyses and probability sensitivity analyses were conducted. For treating invasive candidiasis (all species), as compared to fluconazole, micafungin and caspofungin are dominated (less effective, more expensive), whereas anidulafungin is cost-effective (more effective, more expensive), costing US$3666.09 for each life-year gained, which was below the implicit threshold of the incremental cost-effectiveness ratio in Taiwan. For C. albicans, echinocandins are cost-saving as compared to non-echinocandins. For non-albicans Candida species, echinocandins are cost-effective as compared to non-echinocandins, costing US$652 for each life-year gained. The results were robust over a wide range of sensitivity analyses and were most sensitive to the clinical efficacy of antifungal treatment. Echinocandins, especially anidulafungin, appear to be cost-effective for invasive candidiasis caused by C. albicans and non-albicans Candida species in Taiwan.

  4. Antimicrobial activity of plant extracts on Candida albicans: an in vitro study.

    Science.gov (United States)

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

    2013-01-01

    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. 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. 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. 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.

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

    Directory of Open Access Journals (Sweden)

    Sunitha Jagalur Doddanna

    2013-01-01

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

  6. Candida albicans spondylodiscitis following an abdominal stab wound: forensic considerations.

    Science.gov (United States)

    Savall, Frederic; Dedouit, Fabrice; Telmon, Norbert; Rougé, Daniel

    2014-03-01

    Candida albicans spondylodiscitis is a fungal infection of the spine which is still unusual in spite of the increasing frequency of predisposing factors. A 22-year-old man received an abdominal stab wound during a physical assault. Initial medical care included surgery, prolonged use of indwelling vascular catheters with administration of broad-spectrum antibiotics, and hospitalization in intensive care. Two months after the event, the victim experienced back pain in the right lumbar region and septic spondylodiscitis secondary to C. albicans was diagnosed three weeks later. This case is noteworthy because of its clinical forensic context. In France, the public prosecutor orders a medico-legal assessment after an assault for all living victims in order to establish a causal relationship between the assault and its complications. In our case, the patient presented numerous risk factors for candidemia and the forensic specialist reasonably accepted that the causal relationship was certain but indirect. We have only found one published case of spondylodiscitis after an abdominal penetrating injury and the pathogenic agent was not mentioned. We have found no case reported in a forensic context. This unusual observation shows that it may be genuinely difficult to prove the causal relationship between an abdominal penetrating injury and an unusual infectious complication such as fungal spondylodiscitis. Copyright © 2014 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  7. Stimulation of chitin synthesis rescues Candida albicans from echinocandins.

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    Louise A Walker

    2008-04-01

    Full Text Available Echinocandins are a new generation of novel antifungal agent that inhibit cell wall beta(1,3-glucan synthesis and are normally cidal for the human pathogen Candida albicans. Treatment of C. albicans with low levels of echinocandins stimulated chitin synthase (CHS gene expression, increased Chs activity, elevated chitin content and reduced efficacy of these drugs. Elevation of chitin synthesis was mediated via the PKC, HOG, and Ca(2+-calcineurin signalling pathways. Stimulation of Chs2p and Chs8p by activators of these pathways enabled cells to survive otherwise lethal concentrations of echinocandins, even in the absence of Chs3p and the normally essential Chs1p, which synthesize the chitinous septal ring and primary septum of the fungus. Under such conditions, a novel proximally offset septum was synthesized that restored the capacity for cell division, sustained the viability of the cell, and abrogated morphological and growth defects associated with echinocandin treatment and the chs mutations. These findings anticipate potential resistance mechanisms to echinocandins. However, echinocandins and chitin synthase inhibitors synergized strongly, highlighting the potential for combination therapies with greatly enhanced cidal activity.

  8. [Candida albicans endocarditis after treatment of complete atrioventricular canal].

    Science.gov (United States)

    El Alami, S; Handor, N; Moutaki Allah, Y; Bouchrik, M; El Mellouki, W; Boulahya, A; Lmimouni, B

    2013-09-01

    Infective endocarditis is rare in children, it is rarer after a surgical treatment of atrioventricular canal, and it is exceptional that Candida albicans is the etiologic agent. This is a serious infection found in congenital heart disease with or without surgery. It is potentially lethal, despite diagnostic and therapeutic advances. We report a case of infective endocarditis due to C. albicans after the treatment of a congenital systemic atrioventricular canal in a child with trisomy 21. The diagnosis was suspected on clinical manifestations and cardiac auscultation. Confirmation was provided by positive blood cultures and echocardiography. The large size of the vegetation in the patient was in favor of a fungal etiology, blood cultures allowed to identify the fungus. This observation illustrates a poorly understood disease, with very poor prognosis and which is a potential complication of heart surgery. The improved prognosis should be achieved by shortening the time to diagnosis and optimizing the therapeutic support. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Weitz, Iris S.; Maoz, Michal; Panitz, Daniel; Eichler, Sigal; Segal, Ester

    2015-08-01

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

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

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    Anand Srinivasan

    2011-04-01

    Full Text Available We have developed a high-density microarray platform consisting of nano-biofilms of Candida albicans. A robotic microarrayer was used to print yeast cells of C. albicans encapsulated in a collagen matrix at a volume as low as 50 nL onto surface-modified microscope slides. Upon incubation, the cells grow into fully formed "nano-biofilms". The morphological and architectural complexity of these biofilms were evaluated by scanning electron and confocal scanning laser microscopy. The extent of biofilm formation was determined using a microarray scanner from changes in fluorescence intensities due to FUN 1 metabolic processing. This staining technique was also adapted for antifungal susceptibility testing, which demonstrated that, similar to regular biofilms, cells within the on-chip biofilms displayed elevated levels of resistance against antifungal agents (fluconazole and amphotericin B. Thus, results from structural analyses and antifungal susceptibility testing indicated that despite miniaturization, these biofilms display the typical phenotypic properties associated with the biofilm mode of growth. In its final format, the C. albicans biofilm chip (CaBChip is composed of 768 equivalent and spatially distinct nano-biofilms on a single slide; multiple chips can be printed and processed simultaneously. Compared to current methods for the formation of microbial biofilms, namely the 96-well microtiter plate model, this fungal biofilm chip has advantages in terms of miniaturization and automation, which combine to cut reagent use and analysis time, minimize labor intensive steps, and dramatically reduce assay costs. Such a chip should accelerate the antifungal drug discovery process by enabling rapid, convenient and inexpensive screening of hundreds-to-thousands of compounds simultaneously.

  12. Candida albicans interface infection after deep anterior lamellar keratoplasty

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    Mohammad Reza Sedaghat

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Stamenov N.

    2016-03-01

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

  14. 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.

  15. Effect of essential oils prepared from Thai culinary herbs on sessile Candida albicans cultures

    National Research Council Canada - National Science Library

    Hovijitra, Ray S; Choonharuangdej, Suwan; Srithavaj, Theerathavaj

    2016-01-01

    ... elucidated. Therefore, it is noteworthy to determine the antifungal efficacy of some edible herbs used in Thai cuisine against sessile Candida albicans cultures, and to inquire if they can be further utilized...

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

    National Research Council Canada - National Science Library

    Wheeler, Robert T; Kombe, Diana; Agarwala, Sudeep D; Fink, Gerald R

    2008-01-01

    Candida albicans, a clinically important dimorphic fungal pathogen that can evade immune attack by masking its cell wall beta-glucan from immune recognition, mutes protective host responses mediated...

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

    National Research Council Canada - National Science Library

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

    2014-01-01

    .... 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...

  18. The Pho4 transcription factor mediates the response to arsenate and arsenite in Candida albicans

    Directory of Open Access Journals (Sweden)

    Veronica eUrrialde

    2015-02-01

    Full Text Available Arsenate (As (V is the dominant form of the toxic metalloid arsenic (As. Microorganisms have consequently developed mechanisms to detoxify and tolerate this kind of compounds. In the present work, we have explored the arsenate sensing and signaling mechanisms in the pathogenic fungus Candida albicans. Although mutants impaired in the Hog1 or Mkc1-mediated pathways did not show significant sensitivity to this compound, both Hog1 and Mkc1 became phosphorylated upon addition of sodium arsenate to growing cells. Hog1 phosphorylation upon arsenate challenge was shown to be Ssk1-dependent. A screening designed for the identification of transcription factors involved in the arsenate response identified Pho4, a transcription factor of the myc-family, as pho4 mutants were susceptible to As (V. The expression of PHO4 was shortly induced in the presence of sodium arsenate in a Hog1-independent manner. Pho4 level affects Hog1 phosphorylation upon As (V challenge, suggesting an indirect relationship between Pho4 activity and signaling in C. albicans. Pho4 also mediates the response to arsenite as revealed by the fact that pho4 defective mutants are sensitive to arsenite and Pho4 becomes phosphorylated upon sodium arsenite addition. Arsenite also triggers Hog1 phosphorylation by a process that is, in this case, independent of the Ssk1 kinase. These results indicate that the HOG pathway mediates the response to arsenate and arsenite in C. albicans and that the Pho4 transcription factor can differentiate among As (III, As (V and Pi, triggering presumably specific responses.

  19. Candida albicans possesses Sap7 as a pepstatin A-insensitive secreted aspartic protease.

    Directory of Open Access Journals (Sweden)

    Wataru Aoki

    Full Text Available BACKGROUND: Candida albicans, a commensal organism, is a part of the normal flora of healthy individuals. However, once the host immunity is compromised, C. albicans opportunistically causes recurrent superficial or fatal systemic candidiasis. Secreted aspartic proteases (Sap, encoded by 10 types of SAP genes, have been suggested to contribute to various virulence processes. Thus, it is important to elucidate their biochemical properties for better understanding of the molecular mechanisms that how Sap isozymes damage host tissues. METHODOLOGY/PRINCIPAL FINDINGS: The SAP7 gene was cloned from C. albicans SC5314 and heterogeneously produced by Pichia pastoris. Measurement of Sap7 proteolytic activity using the FRETS-25Ala library showed that Sap7 was a pepstatin A-insensitive protease. To understand why Sap7 was insensitive to pepstatin A, alanine substitution mutants of Sap7 were constructed. We found that M242A and T467A mutants had normal proteolytic activity and sensitivity to pepstatin A. M242 and T467 were located in close proximity to the entrance to an active site, and alanine substitution at these positions widened the entrance. Our results suggest that this alteration might allow increased accessibility of pepstatin A to the active site. This inference was supported by the observation that the T467A mutant has stronger proteolytic activity than the wild type. CONCLUSIONS/SIGNIFICANCE: We found that Sap7 was a pepstatin A-insensitive protease, and that M242 and T467 restricted the accessibility of pepstatin A to the active site. This finding will lead to the development of a novel protease inhibitor beyond pepstatin A. Such a novel inhibitor will be an important research tool as well as pharmaceutical agent for patients suffering from candidiasis.

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

    LENUS (Irish Health Repository)

    Spiering, Martin J

    2010-02-01

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

  1. Comparative Transcript Profiling of Candida albicans and Candida dubliniensis Identifies SFL2, a C. albicans Gene Required for Virulence in a Reconstituted Epithelial Infection Model ▿ †

    Science.gov (United States)

    Spiering, Martin J.; Moran, Gary P.; Chauvel, Murielle; MacCallum, Donna M.; Higgins, Judy; Hokamp, Karsten; Yeomans, Tim; d'Enfert, Christophe; Coleman, David C.; Sullivan, Derek J.

    2010-01-01

    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. ΔΔsfl2 cells failed to filament under a range of hypha-inducing conditions and exhibited greatly reduced RHE damage, reversed by reintroduction of SFL2 into the ΔΔsfl2 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, ΔΔsfl2 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. PMID:20023067

  2. Fungal inhibitory effect of Citrus Limon peel essential oil on Candida albicans

    Directory of Open Access Journals (Sweden)

    Iwan Hernawan

    2015-06-01

    Full Text Available Background: Oral candidiasis is an opportunistic infections due to Candida albicans that often found in people with HIV/AIDS. Anti-fungi, polyne and azole, are used in the treatment of oral candidiasis, but often cause persistence and recurrence. Citrus Limon peel contains terpenoids capable of inhibiting the synthesis of ergosterol, a component of the fungal cell wall that helps to maintain cell membrane permeability. Essential oil derived from citrus limon peel, thus, is expected to inhibit the growth of Candida albicans. Purpose: This research was aimed to know how essential oil derived from citrus Limon peel can inhibit the growth of Candida albicans. Method: This research was a laboratory experimental research carried out in three phases. First, essential oil was made with cold pressing method, and then the concentration of 100% was diluted to 50%, 12.5%, 6.25%, 3.125%, 1.56% and 0.78%. A test was conducted on the culture of Candida albicans in Sabouraud broth, accompanied by control (+ and (-. Second, the dilution of essential oil was conducted to alter the concentration with inhibitory power, from the strongest one to the weakest one, and then it was tested on the culture of Candida albicans. Third, spreading was carried out from liquid culture to agar media in order to measure the number of colonies. Result: Candida albicans did not grow on media with 100% essential oil treatment, but it grew on media with 50% essential oil treatment. In the second phase, dilution of 100%, 90%, 80%, 70%, 60% and 50% was conducted. The growth of Candida albicans was found on the treatment media of 60% and 50%. On the agar media, the growth occurred in the cultured medium treated with 70%. Conclusion: The minimum inhibitory power of essential oil derived from citrus Limon peel against Candida albicans was in the concentration of 80%. Essential oil derived from citrus Limon peel has antifungal effect and potential as a therapeutic agent for oral candidiasis.

  3. Screening the Pathogen Box for Identification of Candida albicans Biofilm Inhibitors

    OpenAIRE

    Vila, Taissa; Lopez-Ribot, Jose L.

    2016-01-01

    Candida albicans remains the main causative agent of candidiasis, one of the most frequent nosocomial infections, with unacceptably high mortality rates. Biofilm formation is a major risk factor for invasive candidiasis, as Candida biofilms display high-level resistance to most antifungal agents. In this work we have screened the Pathogen Box chemical library (Medicines for Malaria Venture [MMV], Switzerland) in search for inhibitors of C. albicans biofilm formation. Our initial screen identi...

  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. © 2014 Blackwell Verlag GmbH.

  5. In vitro activity of micafungin against biofilms of Candida albicans, Candida glabrata, and Candida parapsilosis at different stages of maturation.

    Science.gov (United States)

    Prażyńska, Małgorzata; Bogiel, Tomasz; Gospodarek-Komkowska, Eugenia

    2018-03-01

    Candida spp. is able to form a biofilm, which is considered resistant to the majority of antifungals used in medicine. The aim of this study was to evaluate the in vitro activity of micafungin against Candida spp. biofilms at different stages of their maturation (2, 6, and 24 h). We assessed the inhibitory effect of micafungin against 78 clinical isolates of Candida spp., growing as planktonic or sessile cells, by widely recommended broth microdilution method. The in vitro effect on sessile cells viability was evaluated by colorimetric reduction assay. All examined strains were susceptible or intermediate to micafungin when growing as planktonic cells. At the early stages of biofilm maturation, from 11 (39.3%) to 20 (100%), tested strains, depending on the species, exhibited sessile minimal inhibitory concentrations (SMICs) of micafungin at ≤ 2 mg/L. For 24-h-old Candida spp. biofilms, from 3 (10.7%) to 20 (100%) of the tested strains displayed SMICs of micafungin at ≤ 2 mg/L. Our findings confirm that micafungin exhibits high potential anti-Candida-biofilm activity. However, this effect does not comprise all Candida species and strains. All strains were susceptible or intermediate to micafungin when growing as planktonic cells, but for biofilms, micafungin displays species- and strain-specific activity. Paradoxical growth of C. albicans and C. parapsilosis was observed. Antifungal susceptibility testing of Candida spp. biofilms would be the best solution, but to date, no reference method is available. The strongest antibiofilm activity of micafungin is observed at early stages of biofilm formation. Possibly, micafungin could be considered as an effective agent for prevention of biofilm-associated candidiasis, especially catheter-related candidaemia.

  6. Candida albicans SH3-domain proteins involved in hyphal growth, cytokinesis, and vacuolar morphology.

    Science.gov (United States)

    Reijnst, Patrick; Jorde, Sigyn; Wendland, Jürgen

    2010-08-01

    This report describes the analyses of three Candida albicans genes that encode Src Homology 3 (SH3)-domain proteins. Homologs in Saccharomyces cerevisiae are encoded by the SLA1, NBP2, and CYK3 genes. Deletion of CYK3 in C. albicans was not feasible, suggesting it is essential. Promoter shutdown experiments of CaCYK3 revealed cytokinesis defects, which are in line with the localization of GFP-tagged Cyk3 at septal sites. Deletion of SLA1 resulted in strains with decreased ability to form hyphal filaments. The number of cortical actin patches was strongly reduced in Deltasla1 strains during all growth stages. Sla1-GFP localizes in patches that are found concentrated at the hyphal tip. Deletion of the first two SH3-domains of Sla1 still resulted in cortical localization of the truncated protein. However, the actin cytoskeleton in this strain was aberrant like in the Deltasla1 deletion mutant indicating a function of these SH3 domains to recruit actin nucleation to sites of endocytosis. Deletion of NBP2 resulted in a defect in vacuolar fusion in hyphae. Germ cells of Deltanbp2 strains lacked a large vacuole but initiated several germ tubes. The mutant phenotypes of Deltanbp2 and Deltasla1 could be corrected by reintegration of the wild-type genes.

  7. Candida albicans adherence and proliferation on the surface of denture base materials.

    Science.gov (United States)

    Koch, Carola; Bürgers, Ralf; Hahnel, Sebastian

    2013-12-01

    This study aimed to evaluate the adhesion and proliferation of Candida albicans on denture base materials with different resin chemistries. Standardised specimens were prepared from different denture base materials (i.e. Palapress vario, Paladon 65, Castdon, Sherapress, Eclipse and Mucopren) and subjected to thermal cycling to simulate an artificial ageing process. After the determination of surface roughness and surface free energy, Candida albicans adherence and proliferation on the surface of denture base materials were simulated by subsequent incubation with Candida albicans ATCC 10231 for either 24 h or 196 h with and without prior simulation of salivary pellicle formation. Regardless of the presence of a salivary pellicle or the incubation time, the results indicate that the proliferation of Candida albicans is significantly dependent on the material that is used for the fabrication of denture bases (p materials with the highest polar contribution to surface free energy (i.e. Eclipse, Mucopren), and this result supports the assumption that there might be a relationship between the polar contribution to surface free energy of the substratum material and Candida albicans proliferation. The results obtained from this study indicate that Candida albicans proliferation in particular is not necessarily increased on denture base materials that are subjected to thermal cycling. © 2013 John Wiley & Sons A/S and The Gerodontology Society. Published by John Wiley & Sons Ltd.

  8. An in vitro antifungal efficacy of silver nanoparticles activated by diode laser to Candida albicans

    Science.gov (United States)

    Astuti, S. D.; Kharisma, D. H.; Kholimatussa'diah, S.; Zaidan, A. H.

    2017-09-01

    Microbial infectious diseases and increased resistance to antibiotics become urgent problems requiring immediate solutions. One promising alternative is the using of silver nanoparticles. The combination of the microbial inhibition characteristic of silver nanotechnology enhances the activity of antimicrobial effect. This study aims to determine effectiveness of antifungal silver nanoparticles with the activation of the diode laser on Candida albicans. The samples were culture of Candida albicans. Candida albicans cultures were incubated with silver nanoparticles (concentration 10-4 M) and treated with various exposure time of diode laser (15, 30, 45, 60, 75, 90)s. The suspension was planted on Sabouraud Dextrone Agar sterile media and incubated for 24 hours at temperature of 37oC. The number of colony-forming units per milliliter (CFU/ml) was determined after incubation. The results were log-transformed and analyzed by analysis of variance (ANOVA). In this analysis, P value ≤0.05 was considered to indicate a statistically significant difference. The result of this study showed the quantum yield of silver nanoparticles with diode laser 450 nm was 63,61%. Irradiating with diode laser 450 nm for 75 s resulted in the highest decreasing percentage of Candida albicans viability 65,03%. Irradiating with diode laser 450 nm 75 s with silver nanoparticles resulted in the higest decreasing percentage of Candida albicans viability 84,63%. Therefore, silver nanoparticles activated with diode laser irradiation of 450 nm resulted antifungal effect to Candida albicans viability.

  9. The MARVEL domain protein Nce102 regulates actin organization and invasive growth of Candida albicans.

    Science.gov (United States)

    Douglas, Lois M; Wang, Hong X; Konopka, James B

    2013-11-26

    Invasive growth of the fungal pathogen Candida albicans into tissues promotes disseminated infections in humans. The plasma membrane is essential for pathogenesis because this important barrier mediates morphogenesis and invasive growth, as well as secretion of virulence factors, cell wall synthesis, nutrient import, and other processes. Previous studies showed that the Sur7 tetraspan protein that localizes to MCC (membrane compartment occupied by Can1)/eisosome subdomains of the plasma membrane regulates a broad range of key functions, including cell wall synthesis, morphogenesis, and resistance to copper. Therefore, a distinct tetraspan protein found in MCC/eisosomes, Nce102, was investigated. Nce102 belongs to the MARVEL domain protein family, which is implicated in regulating membrane structure and function. Deletion of NCE102 did not cause the broad defects seen in sur7Δ cells. Instead, the nce102Δ mutant displayed a unique phenotype in that it was defective in forming hyphae and invading low concentrations of agar but could invade well in higher agar concentrations. This phenotype was likely due to a defect in actin organization that was observed by phalloidin staining. In support of this, the invasive growth defect of a bni1Δ mutant that mislocalizes actin due to lack of the Bni1 formin was also reversed at high agar concentrations. This suggests that a denser matrix provides a signal that compensates for the actin defects. The nce102Δ mutant displayed decreased virulence and formed abnormal hyphae in mice. These studies identify novel ways that Nce102 and the physical environment surrounding C. albicans regulate morphogenesis and pathogenesis. The plasma membrane promotes virulence of the human fungal pathogen Candida albicans by acting as a protective barrier around the cell and mediating dynamic activities, such as morphogenesis, cell wall synthesis, secretion of virulence factors, and nutrient uptake. To better understand how the plasma membrane

  10. Whole RNA-Sequencing and Transcriptome Assembly of Candida albicans and Candida africana under Chlamydospore-Inducing Conditions.

    Science.gov (United States)

    Giosa, Domenico; Felice, Maria Rosa; Lawrence, Travis J; Gulati, Megha; Scordino, Fabio; Giuffrè, Letterio; Lo Passo, Carla; D'Alessandro, Enrico; Criseo, Giuseppe; Ardell, David H; Hernday, Aaron D; Nobile, Clarissa J; Romeo, Orazio

    2017-07-01

    Candida albicans is the most common cause of life-threatening fungal infections in humans, especially in immunocompromised individuals. Crucial to its success as an opportunistic pathogen is the considerable dynamism of its genome, which readily undergoes genetic changes generating new phenotypes and shaping the evolution of new strains. Candida africana is an intriguing C. albicans biovariant strain that exhibits remarkable genetic and phenotypic differences when compared with standard C. albicans isolates. Candida africana is well-known for its low degree of virulence compared with C. albicans and for its inability to produce chlamydospores that C. albicans, characteristically, produces under certain environmental conditions. Chlamydospores are large, spherical structures, whose biological function is still unknown. For this reason, we have sequenced, assembled, and annotated the whole transcriptomes obtained from an efficient C. albicans chlamydospore-producing clinical strain (GE1), compared with the natural chlamydospore-negative C. africana clinical strain (CBS 11016). The transcriptomes of both C. albicans (GE1) and C. africana (CBS 11016) clinical strains, grown under chlamydospore-inducing conditions, were sequenced and assembled into 7,442 (GE1 strain) and 8,370 (CBS 11016 strain) high quality transcripts, respectively. The release of the first assembly of the C. africana transcriptome will allow future comparative studies to better understand the biology and evolution of this important human fungal pathogen. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  11. Isolation of a germ-tube-forming revertant from Candida albicans B311V6.

    OpenAIRE

    Buckley, H R; Daneo-Moore, L; Ahrens, J C; Sobel, J D

    1986-01-01

    We describe and partially characterize the isolation of a germ-tube-positive revertant from Candida albicans B311V6. This revertant has all of the properties of a germ-tube-forming strain of C. albicans except that it appears to have a nutrition defect.

  12. 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

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

    NARCIS (Netherlands)

    Ophelders, D.R.; Gussenhoven, R.; Lammens, M.; Kusters, B.; Kemp, M.W.; Newnham, J.P.; Payne, M.S.; Kallapur, S.G.; Jobe, A.H.; Zimmermann, L.J.; Kramer, B.W.; Wolfs, T.G.

    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

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

    NARCIS (Netherlands)

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

    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

  15. 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 ...

  16. 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...

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

    NARCIS (Netherlands)

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

    2012-01-01

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

  18. 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.

  19. 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.

  20. 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

    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...

  1. A Candida albicans early stage biofilm detachment event in rich medium

    Directory of Open Access Journals (Sweden)

    Nantel Andre

    2009-02-01

    Full Text Available Abstract Background Dispersal from Candida albicans biofilms that colonize catheters is implicated as a primary factor in the link between contaminated catheters and life threatening blood stream infections (BSI. Appropriate in vitro C. albicans biofilm models are needed to probe factors that induce detachment events. Results Using a flow through system to culture C. albicans biofilms we characterized a detachment process which culminates in dissociation of an entire early stage biofilm from a silicone elastomer surface. We analyzed the transcriptome response at time points that bracketed an abrupt transition in which a strong adhesive association with the surface is weakened in the initial stages of the process, and also compared batch and biofilm cultures at relevant time points. K means analysis of the time course array data revealed categories of genes with similar patterns of expression that were associated with adhesion, biofilm formation and glycoprotein biosynthesis. Compared to batch cultures the biofilm showed a pattern of expression of metabolic genes that was similar to the C. albicans response to hypoxia. However, the loss of strong adhesion was not obviously influenced by either the availability of oxygen in the medium or at the silicone elastomer surface. The detachment phenotype of mutant strains in which selected genes were either deleted or overexpressed was characterized. The microarray data indicated that changes associated with the detachment process were complex and, consistent with this assessment, we were unable to demonstrate that transcriptional regulation of any single gene was essential for loss of the strong adhesive association. Conclusion The massive dispersal of the early stage biofilm from a biomaterial surface that we observed is not orchestrated at the level of transcriptional regulation in an obvious manner, or is only regulated at this level by a small subpopulation of cells that mediate adhesion to the

  2. 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 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 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.

  3. Epidemiology of Candida albicans and non-C.albicans of neonatal candidemia at a tertiary care hospital in western China.

    Science.gov (United States)

    Fu, Jinjian; Ding, Yanling; Wei, Ba; Wang, Lin; Xu, Shaolin; Qin, Peixu; Wei, Liuhua; Jiang, Lijun

    2017-05-06

    Although the majority of Candida infections occur in the developing world, candidemia epidemiology is poorly understood in these countries. The aim of this study was to investigate the epidemiology of non-Candida albicans (non-C. albicans) candidemia among neonates at Liuzhou Maternity and Child Healthcare Hospital in China. A retrospective review of all positive blood culture about Candida species in neonatal intensive care unit was conducted between January 2012 and November 2015. Information about demographics, risk factors and outcome of candidemia were collected. Univariate and multivariate logistic regression models were used to identify the risk factors associated with the development of non-C.albicans candidemia. The prevalence of candidemia in infants was 1.4%. Non-C.albicans was responsible for 56.5% of neonatal candidemia. The predisposing factors for development of non-C.albicans candidemia among infants included mechanical ventilation [odds ratio (OR), 95% confidence interval (95%CI) = 3.13, 1.07-9.14; P = 0.037] and use of assisted reproductive technology (OR, 95%CI = 4.52, 1.39-14.77; P = 0.012). The overall mortality rate of candidemia was 8.7% and non-C.albicans attributed to 83.3% of all mortalities. Non-C.albicans species are the major cause of candidemia in local neonatal group. The study highlights the urgent needs to evaluate the possibility of development of non-C.albicans candidemia in neonates exposed to these risk factors and much emphasis must be laid on the early implementation of medical intervention to reduce the incidences of candidemia in neonates.

  4. Unequal contribution of ALS9 alleles to adhesion between Candida albicans and human vascular endothelial cells.

    Science.gov (United States)

    Zhao, Xiaomin; Oh, Soon-Hwan; Hoyer, Lois L

    2007-07-01

    The Candida albicans ALS (agglutinin-like sequence) family includes eight genes (ALS1 to ALS7, and ALS9) that share a common general organization, consisting of a relatively conserved 5' domain, a central domain of tandemly repeated sequence units, and a 3' domain of relatively variable length and sequence. To test the hypothesis that the cell-surface glycoproteins encoded by the ALS genes mediate contact between the fungal cell and host surfaces, a set of C. albicans mutant strains was systematically constructed, each lacking one of the ALS sequences. Phenotypes of the mutant strains were evaluated, primarily using adhesion assays. ALS9 is unique within the ALS family due to extensive allelic sequence variation within the 5' domain that may result in functional differences between proteins encoded by ALS9-1 and ALS9-2. Deletion of ALS9 significantly reduces C. albicans adhesion to human vascular endothelial cell monolayers. The mutation was complemented by reintegration of a wild-type copy of ALS9-2, but not ALS9-1, suggesting allelic functional differences. Complementation of the mutation with a gene fusion between the 5' domain of ALS9-2 and the tandem repeats and 3' domain of ALS9-1 also restored wild-type adhesion levels. Analysis of the als9Delta/als9Delta mutant phenotype in other assays demonstrated no significant difference from a control strain for adhesion to buccal epithelial cells or laminin-coated plastic plates. The als9Delta/als9Delta mutant did not show significant differences from the control for adhesion to or destruction of cells in the reconstituted human epithelium (RHE) disease model, or for cell-wall defects, germ-tube formation or biofilm formation in a catheter model. Analysis of ALS9 allelic frequency in a collection of geographically diverse clinical isolates showed a distinct preference for ALS9-2 allelic sequences, within both the 5' and the 3' domain of the ALS9 coding region. These data suggest greater selective pressure to maintain

  5. Direct identification and recognition of yeast species from clinical material by using albicans ID and CHROMagar Candida plates.

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    Baumgartner, C; Freydiere, A. M.; Gille, Y.

    1996-01-01

    Two chromogenic media, Albicans ID and CHROMagar Candida agar plates, were compared with a reference medium, Sabouraud-chloramphenicol agar, and standard methods for the identification of yeast species. This study involved 951 clinical specimens. The detection rates for the two chromogenic media for polymicrobial specimens were 20% higher than that for the Sabouraud-chloramphenicol agar plates. The rates of identification of Candida albicans for Albicans ID and CHROMagar Candida agar plates w...

  6. Evaluation of adhesive properties of Candida albicans isolated from the oral cavity in HIV positive patients.

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    Macura, A B; Bort, A

    2001-01-01

    The aim of the work was to compare adhesive properties of Candida albicans strains isolated from the oral cavity in HIV+ vs. HIV- persons. The materials were Candida albicans strains and buccal epithelial cells isolated from both HIV+ and HIV- persons. We applied the in vitro adherence test, primarily described by Kimura and Pearsall and modified by Macura. The strongest adherence was found between both fungi and epithelial cells isolated from a HIV+ person. The adherence of C. albicans isolated from HIV+ patients was significantly stronger to epithelium collected from HIV+ than HIV- persons.

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

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    Ying-Lien Chen

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

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

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

    2012-09-25

    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. 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. 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. 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 testing for germ tube formation or latex Candida agglutination.

  9. Disruption of the Transcriptional Regulator Cas5 Results in Enhanced Killing of Candida albicans by Fluconazole

    Science.gov (United States)

    Vasicek, Erin M.; Berkow, Elizabeth L.; Bruno, Vincent M.; Mitchell, Aaron P.; Wiederhold, Nathan P.; Barker, Katherine S.

    2014-01-01

    Azole antifungal agents such as fluconazole exhibit fungistatic activity against Candida albicans. Strategies to enhance azole antifungal activity would be therapeutically appealing. In an effort to identify transcriptional pathways that influence the killing activity of fluconazole, we sought to identify transcription factors (TFs) involved in this process. From a collection of C. albicans strains disrupted for genes encoding TFs (O. R. Homann, J. Dea, S. M. Noble, and A. D. Johnson, PLoS Genet. 5:e1000783, 2009, http://dx.doi.org/10.1371/journal.pgen.1000783), four strains exhibited marked reductions in minimum fungicidal concentration (MFCs) in both RPMI and yeast extract-peptone-dextrose (YPD) media. One of these genes, UPC2, was previously characterized with regard to its role in azole susceptibility. Of mutants representing the three remaining TF genes of interest, one (CAS5) was unable to recover from fluconazole exposure at concentrations as low as 2 μg/ml after 72 h in YPD medium. This mutant also showed reduced susceptibility and a clear zone of inhibition by Etest, was unable to grow on solid medium containing 10 μg/ml fluconazole, and exhibited increased susceptibility by time-kill analysis. CAS5 disruption in highly azole-resistant clinical isolates exhibiting multiple resistance mechanisms did not alter susceptibility. However, CAS5 disruption in strains with specific resistance mutations resulted in moderate reductions in MICs and MFCs. Genome-wide transcriptional analysis was performed in the presence of fluconazole and was consistent with the suggested role of CAS5 in cell wall organization while also suggesting a role in iron transport and homeostasis. These findings suggest that Cas5 regulates a transcriptional network that influences the response of C. albicans to fluconazole. Further delineation of this transcriptional network may identify targets for potential cotherapeutic strategies to enhance the activity of the azole class of antifungals

  10. Disruption of the transcriptional regulator Cas5 results in enhanced killing of Candida albicans by Fluconazole.

    Science.gov (United States)

    Vasicek, Erin M; Berkow, Elizabeth L; Bruno, Vincent M; Mitchell, Aaron P; Wiederhold, Nathan P; Barker, Katherine S; Rogers, P David

    2014-11-01

    Azole antifungal agents such as fluconazole exhibit fungistatic activity against Candida albicans. Strategies to enhance azole antifungal activity would be therapeutically appealing. In an effort to identify transcriptional pathways that influence the killing activity of fluconazole, we sought to identify transcription factors (TFs) involved in this process. From a collection of C. albicans strains disrupted for genes encoding TFs (O. R. Homann, J. Dea, S. M. Noble, and A. D. Johnson, PLoS Genet. 5:e1000783, 2009, http://dx.doi.org/10.1371/journal.pgen.1000783), four strains exhibited marked reductions in minimum fungicidal concentration (MFCs) in both RPMI and yeast extract-peptone-dextrose (YPD) media. One of these genes, UPC2, was previously characterized with regard to its role in azole susceptibility. Of mutants representing the three remaining TF genes of interest, one (CAS5) was unable to recover from fluconazole exposure at concentrations as low as 2 μg/ml after 72 h in YPD medium. This mutant also showed reduced susceptibility and a clear zone of inhibition by Etest, was unable to grow on solid medium containing 10 μg/ml fluconazole, and exhibited increased susceptibility by time-kill analysis. CAS5 disruption in highly azole-resistant clinical isolates exhibiting multiple resistance mechanisms did not alter susceptibility. However, CAS5 disruption in strains with specific resistance mutations resulted in moderate reductions in MICs and MFCs. Genome-wide transcriptional analysis was performed in the presence of fluconazole and was consistent with the suggested role of CAS5 in cell wall organization while also suggesting a role in iron transport and homeostasis. These findings suggest that Cas5 regulates a transcriptional network that influences the response of C. albicans to fluconazole. Further delineation of this transcriptional network may identify targets for potential cotherapeutic strategies to enhance the activity of the azole class of antifungals

  11. Evaluation of CAMP-Like Effect, Biofilm Formation, and Discrimination of Candida africana from Vaginal Candida albicans Species

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    Keyvan Pakshir

    2017-01-01

    Full Text Available Candida africana as a species recovered from female genital specimens is highly close to C. albicans. The present study was conducted to discriminate C. africana from presumptive vaginal C. albicans strains by molecular assay and evaluate their hemolysin activity, biofilm formation, and cohemolytic effect (CAMP with vaginal bacterial flora. A total of 110 stock vaginal C. albicans isolates were examined by HWP1 gene amplification. Hemolysin activity and the ability of biofilm formation were evaluated by blood plate assay and visual detection methods, respectively. Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus agalactiae were used to evaluate the CAMP-like effects in Sabouraud blood agar media. Based on the size of the amplicons (941 bp, all isolates were identified as C. albicans. All samples were able to produce beta-hemolysin. Moreover, 69 out of 110 of the isolates (62.7% were biofilm-positive, 54 out of 110 Candida isolates (49% demonstrated cohemolytic effects with S. agalactiae, and 48 out of 110 showed this effect with S. aureus (43.6%. All isolates were CAMP-negative with S. epidermidis. We detected all isolates as Candida albicans and almost half of the isolates were CAMP-positive with S. aureus and S. agalactiae, suggesting that these bacteria increase the pathogenicity of Candida in vaginal candidiasis.

  12. 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.

  13. 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.

  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. Effects of extracellular DNA from Candida albicans and pneumonia-related pathogens on Candida biofilm formation and hyphal transformation.

    Science.gov (United States)

    Sapaar, B; Nur, A; Hirota, K; Yumoto, H; Murakami, K; Amoh, T; Matsuo, T; Ichikawa, T; Miyake, Y

    2014-06-01

    The aim of this study was to investigate the effects of genomic DNA purified from Candida albicans and pneumonia-related pathogens, Pseudomonas aeruginosa and Staphylococcus aureus, on in vitro biofilm formation and morphological change of 3 Candida species (C. albicans, C. glabrata, and C. tropicalis). Biofilm formation was evaluated by the crystal violet assay and colony-forming unit counts. Morphological characteristics of biofilms were evaluated by scanning electron microscopy and fluorescence microscopy. Addition of DNA at a low concentration (Candida species. In contrast, the addition of DNA at a high concentration (10 μg ml(-1)) decreased the biofilm mass. Interestingly, the formation of hyphae in a dense network of yeast cells was observed in C. albicans biofilms exposed to a low concentration of DNA (Candida biofilm formation and suggested that eDNA may induce the morphological transition from yeast to hyphal growth form during C. albicans biofilm development. A novel therapy targeting eDNA may be applicable for Candida infection to decrease biofilm formation and hyphal formation. © 2014 The Society for Applied Microbiology.

  16. The antibacterial agent, moxifloxacin inhibits virulence factors of Candida albicans through multitargeting.

    Science.gov (United States)

    Jadhav, Ashwini; Bansode, Bhagyashree; Phule, Datta; Shelar, Amruta; Patil, Rajendra; Gade, Wasudev; Kharat, Kiran; Karuppayil, Sankunny Mohan

    2017-05-01

    Fluoroquinolines are broad spectrum fourth generation antibiotics. Some of the Fluoroquinolines exhibit antifungal activity. We are reporting the potential mechanism of action of a fluoroquinoline antibiotic, moxifloxacin on the growth, morphogenesis and biofilm formation of the human pathogen Candida albicans. Moxifloxacin was found to be Candidacidal in nature. Moxifloxacin seems to inhibit the yeast to Hyphal morphogenesis by affecting signaling pathways. It arrested the cell cycle of C. albicans at S phase. Docking of moxifloxacin with predicted structure of C. albicans DNA Topoisomerase II suggests that moxifloxacin may bind and inhibit the activity of DNA Topoisomerase II in C. albicans. Moxifloxacin could be used as a dual purpose antibiotic for treating mixed infections caused by bacteria as well as C. albicans. In addition chances of developing moxifloxacin resistance in C. albicans are less considering the fact that moxifloxacin may target multiple steps in yeast to hyphal transition in C. albicans.

  17. Candida non albicans with a High amphotericin B resistance pattern causing candidemia among cancer patients.

    Science.gov (United States)

    Kalantar, Enayatollah; Assadi, Mojan; Pormazaheri, Helen; Hatami, Shiva; Barari, Maryam Agha; Asgari, Esfandiar; Mahmoudi, Elaheh; Kabir, Kourosh; Amin Marashi, Seyed Mahmoud

    2014-01-01

    Many scientists have reported Candida species to be of great concern because of the high frequency that they colonize and infect human hosts, particularly cancer patients. Moreover, in the last decades Candida species have developed resistance to many antifungal agents. Based on this, we aimed to identify and determine the prevalence of Candida spp from blood culture bottles among cancer patients and their antifungal resistance pattern. From the blood culture bottles isolation and identification of the Candida spp were performed by conventional microbiological techniques. The in vitro antibiotic resistance pattern of the isolates was determined by CLSI guidelines. Genomic DNA was isolated and amplified. Each gene was separated by agar gel electrophoresis. Identification of Candida spp was based on the presence of yeast cells in direct examination, culture and DNA extraction. Of the 68 blood samples collected during the study period (April 2013 to October 2013), five (7.35%) were positive for the presence of Candida spp, 2 (40%) of which were identified as Candida albicans and 3 (60%) were Candida non-albicans. High resistance to amphotricin B was observed among all the Candida non-albicans isolates. Regular investigations into antifungal resistance will help us to get an updated knowledge about their antibiotic resistance pattern which may help the physician in selecting the antibiotics for empirical therapy.

  18. Integrating Candida albicans metabolism with biofilm heterogeneity by transcriptome mapping

    Science.gov (United States)

    Rajendran, Ranjith; May, Ali; Sherry, Leighann; Kean, Ryan; Williams, Craig; Jones, Brian L.; Burgess, Karl V.; Heringa, Jaap; Abeln, Sanne; Brandt, Bernd W.; Munro, Carol A.; Ramage, Gordon

    2016-10-01

    Candida albicans biofilm formation is an important virulence factor in the pathogenesis of disease, a characteristic which has been shown to be heterogeneous in clinical isolates. Using an unbiased computational approach we investigated the central metabolic pathways driving biofilm heterogeneity. Transcripts from high (HBF) and low (LBF) biofilm forming isolates were analysed by RNA sequencing, with 6312 genes identified to be expressed in these two phenotypes. With a dedicated computational approach we identified and validated a significantly differentially expressed subnetwork of genes associated with these biofilm phenotypes. Our analysis revealed amino acid metabolism, such as arginine, proline, aspartate and glutamate metabolism, were predominantly upregulated in the HBF phenotype. On the contrary, purine, starch and sucrose metabolism was generally upregulated in the LBF phenotype. The aspartate aminotransferase gene AAT1 was found to be a common member of these amino acid pathways and significantly upregulated in the HBF phenotype. Pharmacological inhibition of AAT1 enzyme activity significantly reduced biofilm formation in a dose-dependent manner. Collectively, these findings provide evidence that biofilm phenotype is associated with differential regulation of metabolic pathways. Understanding and targeting such pathways, such as amino acid metabolism, is potentially useful for developing diagnostics and new antifungals to treat biofilm-based infections.

  19. Photodynamic inactivation of Candida albicans by BAM-SiPc.

    Science.gov (United States)

    So, Cheung-Wai; Tsang, Paul W K; Lo, Pui-Chi; Seneviratne, C J; Samaranayake, Lakshman P; Fong, Wing-Ping

    2010-05-01

    Photodynamic therapy is a treatment that combines the use of three non-toxic components, viz. photosensitiser, light and oxygen to cause localised oxidative photodamage. In the present study, the antifungal effect of the photosensitiser, BAM-SiPc, an unsymmetrical bisamino phthalocyanine, was investigated. BAM-SiPc was effective in photo-inactivating Candida albicans in a dose-dependent manner. The cell viability as determined by the clonogenic assay was reduced to c. 10% at 0.02 micromol l(-1) BAM-SiPc with a total fluence of 12 J cm(-2) at a cell density of 10(7) cells ml(-1). A short incubation time of 5-15 min was sufficient to allow the photosensitiser to exert its optimal antifungal activity. Microscopical analysis showed that BAM-SiPc was effectively internalised by the fungal cells. Photodynamic treatment led to an increase in the intracellular reactive oxygen species level and disturbed the membrane integrity of the fungal cells.

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

    Science.gov (United States)

    Fule, S R; Das, D; Fule, R P

    2015-01-01

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

  1. Candida albicans survival, growth and biofilm formation are differently affected by mouthwashes: an in vitro study.

    Science.gov (United States)

    Paulone, Simona; Malavasi, Giulia; Ardizzoni, Andrea; Orsi, Carlotta Francesca; Peppoloni, Samuele; Neglia, Rachele Giovanna; Blasi, Elisabetta

    2017-01-01

    Candida albicans is the most common cause of oral mycoses. The aim of the present study was to investigate in vitro the susceptibility of C. albicans to mouthwashes, in terms of growth, survival and biofilm formation. Candida albicans, laboratory strain SC5314, and 7 commercial mouthwashes were employed: 3 with 0.2% chlorhexidine digluconate; 1 with 0.06% chlorhexidine digluconate and 250 ppm F- sodium fluoride; 3 with fluorine-containing molecules. None of the mouthwashes contained ethanol in their formulations. The anti-Candida effects of the mouthwashes were assessed by disk diffusion, crystal violet and XTT assays. By using five protocols combining different dilutions and contact times the mouthwashes were tested against: 1) C. albicans growth; 2) biofilm formation; 3) survival of fungal cells in early, developing and mature Candida biofilm. Chlorhexidine digluconate-containing mouthwashes consistently exhibited the highest anti-Candida activity, irrespective of the protocols employed. Fungal growth, biofilm formation and survival of Candida cells within biofilm were impaired, the effects strictly depending on both the dilution employed and the time of contact. These in vitro studies provide evidence that mouthwashes exert anti-Candida activity against both planktonic and biofilm fungal structures, but to a different extent depending on their composition. This suggests special caution in the choice of mouthwashes for oral hygiene, whether aimed at prevention or treatment of oral candidiasis.

  2. Influence of culture conditions for clinically isolated non-albicans Candida biofilm formation.

    Science.gov (United States)

    Tan, Yulong; Leonhard, Matthias; Ma, Su; Schneider-Stickler, Berit

    2016-11-01

    Non-albicans Candida species have been isolated in increasing numbers in patients. Moreover, they are adept at forming biofilms. This study analyzed biofilm formation of clinically isolated non-albicans Candida, including Candida tropicalis, Candida krusei and Candida parapsilosis under the influence of different growth media (RPMI 1640, YPD and BHI) and several culture variables (inoculum concentration, incubation period and feeding conditions). The results showed that culture conditions strongly influenced non-albicans Candida species biofilm formation. YPD and BHI resulted in larger amount of biofilm formation with higher metabolic activity of biofilms. Furthermore, the growth media seems to have varying effects on adhesion and biofilm development. Growth conditions may also influence biofilm formation, which was enhanced when starting the culture with a larger inoculum, longer incubation period and using a fed-batch system. Therefore, the potential influences of external environmental factors should be considered when studying the non-albicans Candida biofilms in vitro. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    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). PMID:25714264

  4. The synthetic killer peptide KP impairs Candida albicans biofilm in vitro.

    Science.gov (United States)

    Paulone, Simona; Ardizzoni, Andrea; Tavanti, Arianna; Piccinelli, Serena; Rizzato, Cosmeri; Lupetti, Antonella; Colombari, Bruna; Pericolini, Eva; Polonelli, Luciano; Magliani, Walter; Conti, Stefania; Posteraro, Brunella; Cermelli, Claudio; Blasi, Elisabetta; Peppoloni, Samuele

    2017-01-01

    Candida albicans is a commensal organism, commonly inhabiting mucosal surfaces of healthy individuals, as a part of the resident microbiota. However, in susceptible hosts, especially hospitalized and/or immunocompromised patients, it may cause a wide range of infections. The presence of abiotic substrates, such as central venous or urinary catheters, provides an additional niche for Candida attachment and persistence, particularly via biofilm development. Furthermore, Candida biofilm is poorly susceptible to most antifungals, including azoles. Here we investigated the effects of a synthetic killer peptide (KP), known to be active in vitro, ex vivo and/or in vivo against different pathogens, on C. albicans biofilm. Together with a scrambled peptide used as a negative control, KP was tested against Candida biofilm at different stages of development. A reference strain, two fluconazole-resistant and two fluconazole-susceptible C. albicans clinical isolates were used. KP-induced C. albicans oxidative stress response and membrane permeability were also analysed. Moreover, the effect of KP on transcriptional profiles of C. albicans genes involved in different stages of biofilm development, such as cell adhesion, hyphal development and extracellular matrix production, was evaluated. Our results clearly show that the treatment with KP strongly affected the capacity of C. albicans to form biofilm and significantly impairs preformed mature biofilm. KP treatment resulted in an increase in C. albicans oxidative stress response and membrane permeability; also, biofilm-related genes expression was significantly reduced. Comparable inhibitory effects were observed in all the strains employed, irrespective of their resistance or susceptibility to fluconazole. Finally, KP-mediated inhibitory effects were observed also against a catheter-associated C. albicans biofilm. This study provides the first evidence on the KP effectiveness against C. albicans biofilm, suggesting that KP may

  5. 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.

  6. Functional specialization and differential regulation of short-chain carboxylic acid transporters in the pathogen Candida albicans.

    Science.gov (United States)

    Vieira, Neide; Casal, Margarida; Johansson, Björn; MacCallum, Donna M; Brown, Alistair J P; Paiva, Sandra

    2010-03-01

    The major fungal pathogen Candida albicans has the metabolic flexibility to assimilate a wide range of nutrients in its human host. Previous studies have suggested that C. albicans can encounter glucose-poor microenvironments during infection and that the ability to use alternative non-fermentable carbon sources contributes to its virulence. JEN1 encodes a monocarboxylate transporter in C. albicans and we show that its paralogue, JEN2, encodes a novel dicarboxylate plasma membrane transporter, subjected to glucose repression. A strain deleted in both genes lost the ability to transport lactic, malic and succinic acids by a mediated mechanism and it displayed a growth defect on these substrates. Although no significant morphogenetic or virulence defects were found in the double mutant strain, both JEN1 and JEN2 were strongly induced during infection. Jen1-GFP (green fluorescent protein) and Jen2-GFP were upregulated following the phagocytosis of C. albicans cells by neutrophils and macrophages, displaying similar behaviour to an Icl1-GFP fusion. In the murine model of systemic candidiasis approximately 20-25% of C. albicans cells infecting the kidney expressed Jen1-GFP and Jen2-GFP. Our data suggest that Jen1 and Jen2 are expressed in glucose-poor niches within the host, and that these short-chain carboxylic acid transporters may be important in the early stages of infection.

  7. Profiling of Candida albicans gene expression during intra-abdominal candidiasis identifies biologic processes involved in pathogenesis.

    Science.gov (United States)

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

    2013-11-01

    The pathogenesis of intra-abdominal candidiasis is poorly understood. Mice were intraperitoneally infected with Candida albicans (1 × 10(6) colony-forming units) and sterile stool. nanoString assays were used to quantitate messenger RNA for 145 C. albicans genes within the peritoneal cavity at 48 hours. Within 6 hours after infection, mice developed peritonitis, characterized by high yeast burdens, neutrophil influx, and a pH of 7.9 within peritoneal fluid. Organ invasion by hyphae and early abscess formation were evident 6 and 24 hours after infection, respectively; abscesses resolved by day 14. nanoString assays revealed adhesion and responses to alkaline pH, osmolarity, and stress as biologic processes activated in the peritoneal cavity. Disruption of the highly-expressed gene RIM101, which encodes an alkaline-regulated transcription factor, did not impact cellular morphology but reduced both C. albicans burden during early peritonitis and C. albicans persistence within abscesses. RIM101 influenced expression of 49 genes during intra-abdominal candidiasis, including previously unidentified Rim101 targets. Overexpression of the RIM101-dependent gene SAP5, which encodes a secreted protease, restored the ability of a rim101 mutant to persist within abscesses. A mouse model of intra-abdominal candidiasis is valuable for studying pathogenesis and C. albicans gene expression. RIM101 contributes to persistence within intra-abdominal abscesses, at least in part through activation of SAP5.

  8. Molecular Identification and Antifungal Susceptibility Pattern of Non-albicans Candida Species Isolated from Vulvovaginal Candidiasis

    Science.gov (United States)

    Abbasi Nejat, Ziba; Farahyar, Shirin; Falahati, Mehraban; Ashrafi Khozani, Mahtab; Hosseini, Aga Fateme; Faiazy, Azamsadat; Ekhtiari, Masoome; Hashemi-Hafshenjani, Saeideh

    2017-07-09

    Vulvovaginal candidiasis (VVC) is an important health problem caused by Candida spp. The aim of this study was molecular identification, phylogenetic analysis, and evaluation of antifungal susceptibility of non-albicans Candida isolates from VVC. Vaginal secretion samples were collected from 550 vaginitis patients at Sayyad Shirazi Medical and Educational Center of Gorgan (Golestan Province, Iran) from May to October 2015. Samples were analyzed using conventional mycological and molecular approaches. Clinical isolates were analyzed with specific PCR using CGL primers, and the internal transcribed spacer region and the D1-D2 domain of the large-subunit rRNA gene were amplified and sequenced. Susceptibility to amphotericin B, fluconazole, itraconazole, and clotrimazole was determined by the guidelines of the Clinical and Laboratory Standard Institute. In total, 35 non-albicans Candida isolates were identified from VVC patients. The isolates included 27 strains of Candida glabrata (77.1%), 5 Candida krusei (Pichia kudriavzevii; 14.3%), 2 Candida kefyr (Kluyveromyces marxianus; 5.7%), and 1 Candida lusitaniae (Clavispora lusitaniae; 2.9%). The fungicides itraconazole and amphotericin B were effective against all species. One isolate of C. glabrata showed resistance to fluconazole and clotrimazole, and 26 isolates of C. glabrata indicated dose-dependent susceptibility to fluconazole. C. lusitaniae was susceptible in a dose-dependent manner to fluconazole and resistant to clotrimazole. Non-albicans Candida spp. are common agents of vulvovaginitis, and C. glabrata is the most common species in the tested patients.

  9. 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.

  10. 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

  11. DAYA HAMBAT MINYAK ATSIRI DAN EKSTRAK LIMBAH SISA DESTILASI RIMPANG KUNIR PUTIH (Kaempferia rotunda L. TERHADAP PERTUMBUHAN Candida albicans ATCC 10231

    Directory of Open Access Journals (Sweden)

    Christina Astutiningsih

    2014-05-01

    was a difference of the zone of inhibition of Candida albicans growth between essential oils and residual distillation of white turmeric rhizome. Keywords: White turmeric, Candida albicans, essential oils, extract of waste, inhibiton.

  12. Neocentromeres form efficiently at multiple possible loci in Candida albicans.

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    Carrie Ketel

    2009-03-01

    Full Text Available Centromeres are critically important for chromosome stability and integrity. Most eukaryotes have regional centromeres that include long tracts of repetitive DNA packaged into pericentric heterochromatin. Neocentromeres, new sites of functional kinetochore assembly, can form at ectopic loci because no DNA sequence is strictly required for assembly of a functional kinetochore. In humans, neocentromeres often arise in cells with gross chromosome rearrangements that rescue an acentric chromosome. Here, we studied the properties of centromeres in Candida albicans, the most prevalent fungal pathogen of humans, which has small regional centromeres that lack pericentric heterochromatin. We functionally delimited centromere DNA on Chromosome 5 (CEN5 and then replaced the entire region with the counter-selectable URA3 gene or other marker genes. All of the resulting cen5Delta::URA3 transformants stably retained both copies of Chr5, indicating that a functional neocentromere had assembled efficiently on the homolog lacking CEN5 DNA. Strains selected to maintain only the cen5Delta::URA3 homolog and no wild-type Chr5 homolog also grew well, indicating that neocentromere function is independent of the presence of any wild-type CEN5 DNA. Two classes of neocentromere (neoCEN strains were distinguishable: "proximal neoCEN" and "distal neoCEN" strains. Neocentromeres in the distal neoCEN strains formed at loci about 200-450 kb from cen5Delta::URA3 on either chromosome arm, as detected by massively parallel sequencing of DNA isolated by CENP-A(Cse4p chromatin immunoprecipitation (ChIP. In the proximal neoCEN strains, the neocentromeres formed directly adjacent to cen5Delta::URA3 and moved onto the URA3 DNA, resulting in silencing of its expression. Functional neocentromeres form efficiently at several possible loci that share properties of low gene density and flanking repeated DNA sequences. Subsequently, neocentromeres can move locally, which can be detected by

  13. Inhibitory effects of oral Actinomyces on the proliferation, virulence and biofilm formation of Candida albicans.

    Science.gov (United States)

    Guo, Yiqing; Wei, Changlei; Liu, Chuanxia; Li, Duo; Sun, Jun; Huang, Haiyun; Zhou, Hongmei

    2015-09-01

    The pathogenesis of Candida-associated stomatitis involves the dysfunction of flora antagonistic to Candida. Oral Actinomyces species play an important role in regulating the oral microecological balance. The objective of this study was to investigate the antagonism of three oral Actinomyces against Candida albicans. Suspensions, culture supernatants and bacterial lysates of Actinomyces viscosus, Actinomyces naeslundii and Actinomyces odontolyticus were investigated for their actions upon C. albicans. In addition to a commercial strain, six clinical strains of C. albicans were also tested. The proliferation of C. albicans was assessed using a liquid co-cultivation assay. The adhesion, acid protease and extracellular phospholipase activity, hyphae growth, and biofilm formation of C. albicans were measured. The results showed that the suspensions, culture supernatants and cell lysates of 10(8) colony forming units/ml oral Actinomyces significantly inhibited the proliferation of C. albicans (all PActinomyces have inhibitory effects on the proliferation, adhesion, metabolic enzyme activity, hyphae formation and biofilm development of C. albicans. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Effects of citrus limon essential oil (Citrus limon L. on cytomorphometric changes of Candida albicans

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    Rina Prabajati

    2017-03-01

    Full Text Available Background: The most common fungal infection found in oral cavity is oral candidiasis, largely caused by Candida species, particularly Candida albicans (C. albicans. Candida infection can get worse since it is difficult to be treated and resistant with antifungal drugs. Therefore, new drugs and compounds as well as alternative therapies involving natural sources that have antifungal activities have continually been developed. Limonene, β-pinene, and ɣ-terpinene contained in Citrus limon essential oil have been known to have quite good antifungal activities against C. albicans. Purpose: This research aimed to examine and analyze the effects of Citrus limon essential oil on cytomorphometric changes of C. albicans. Method: The research used post test only control group design. Based on the results of the pre-elementary research on antifungal activities of Citrus limon essential oil against C. albicans, Citrus limon essential oil used in this research was on concentrations of 1.56%, 1.37%, 1.17%, 0.98%, and 0.78%. Citrus limon essential oil by C. albicans inoculum and incubated for 24 hours and 48 hours. After the incubation, those C. albicans cells were fixed, dried, and then observed using a scanning electron microscopy. Result: The most effective concentrations of Citrus limon essential oil triggering cytomorphometric changes of Candida albicans were at 1.37% and 1.56% with the incubation period of 48 hours. Conclusion: C. albicans can undergo necrosis process through cytomorphometric changes after the administration of Citrus limon essential oil at concentrations of 1.56% and 1.37% with the incubation period of 48 hours.

  15. 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.

  16. The Mkk2 MAPKK Regulates Cell Wall Biogenesis in Cooperation with the Cek1-Pathway in Candida albicans.

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    Elvira Román

    Full Text Available The cell wall integrity pathway (CWI plays an important role in the biogenesis of the cell wall in Candida albicans and other fungi. In the present work, the C. albicans MKK2 gene that encodes the putative MAPKK of this pathway was deleted in different backgrounds and the phenotypes of the resultant mutants were characterised. We show here that Mkk2 mediates the phosphorylation of the Mkc1 MAPK in response to cell wall assembly interfering agents such as zymolyase or tunicamycin and also to oxidative stress. Remarkably, mkk2 and mkc1 mutants display related but distinguishable- cell wall associated phenotypes and differ in the pattern of MAPK phosphorylation under different stress conditions. mkk2 and mkc1 mutants display an altered expression of GSC1, CEK1 and CRH11 genes at different temperatures. Combined deletion of MKK2 with HST7 supports a cooperative role for the Cek1-mediated and CWI pathways in regulating cell wall architecture under vegetative growth. However, and in contrast to Mkc1, Mkk2 does not seem to play a role in the virulence of C. albicans in the mouse systemic model or the Galleria mellonella model of infection.

  17. Cdc24, the GDP-GTP exchange factor for Cdc42, is required for invasive hyphal growth of Candida albicans.

    Science.gov (United States)

    Bassilana, Martine; Blyth, James; Arkowitz, Robert A

    2003-02-01

    Candida albicans, the most common human fungal pathogen, is particularly problematic for immunocompromised individuals. The reversible transition of this fungal pathogen to a filamentous form that invades host tissue is important for its virulence. Although different signaling pathways such as a mitogen-activated protein kinase and a protein kinase A cascade are critical for this morphological transition, the function of polarity establishment proteins in this process has not been determined. We examined the role of four different polarity establishment proteins in C. albicans invasive growth and virulence by using strains in which one copy of each gene was deleted and the other copy expressed behind the regulatable promoter MET3. Strikingly, mutants with ectopic expression of either the Rho G-protein Cdc42 or its exchange factor Cdc24 are unable to form invasive hyphal filaments and germ tubes in response to serum or elevated temperature and yet grow normally as a budding yeast. Furthermore, these mutants are avirulent in a mouse model for systemic infection. This function of the Cdc42 GTPase module is not simply a general feature of polarity establishment proteins. Mutants with ectopic expression of the SH3 domain containing protein Bem1 or the Ras-like G-protein Bud1 can grow in an invasive fashion and are virulent in mice, albeit with reduced efficiency. These results indicate that a specific regulation of Cdc24/Cdc42 activity is required for invasive hyphal growth and suggest that these proteins are required for pathogenicity of C. albicans.

  18. Phosphomannosylation and the Functional Analysis of the Extended Candida albicans MNN4-Like Gene Family

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    Roberto J. González-Hernández

    2017-11-01

    Full Text Available Phosphomannosylation is a modification of cell wall proteins that occurs in some species of yeast-like organisms, including the human pathogen Candida albicans. These modified mannans confer a negative charge to the wall, which is important for the interactions with phagocytic cells of the immune systems and cationic antimicrobial peptides. In Saccharomyces cerevisiae, the synthesis of phosphomannan relies on two enzymes, the phosphomannosyltransferase Ktr6 and its positive regulator Mnn4. However, in C. albicans, at least three phosphomannosyltransferases, Mnn4, Mnt3 and Mnt5, participate in the addition of phosphomannan. In addition to MNN4, C. albicans has a MNN4-like gene family composed of seven other homologous members that have no known function. Here, using the classical mini-Ura-blaster approach and the new gene knockout CRISPR-Cas9 system for gene disruption, we generated mutants lacking single and multiple genes of the MNN4 family; and demonstrate that, although Mnn4 has a major impact on the phosphomannan content, MNN42 was also required for full protein phosphomannosylation. The reintroduction of MNN41, MNN42, MNN46, or MNN47 in a genetic background lacking MNN4 partially restored the phenotype associated with the mnn4Δ null mutant, suggesting that there is partial redundancy of function between some family members and that the dominant effect of MNN4 over other genes could be due to its relative abundance within the cell. We observed that additional copies of alleles number of any of the other family members, with the exception of MNN46, restored the phosphomannan content in cells lacking both MNT3 and MNT5. We, therefore, suggest that phosphomannosylation is achieved by three groups of proteins: [i] enzymes solely activated by Mnn4, [ii] enzymes activated by the dual action of Mnn4 and any of the products of other MNN4-like genes, with exception of MNN46, and [iii] activation of Mnt3 and Mnt5 by Mnn4 and Mnn46. Therefore

  19. Genome-wide transcriptional profiling of the cyclic AMP-dependent signaling pathway during morphogenic transitions of Candida albicans.

    Science.gov (United States)

    Bahn, Yong-Sun; Molenda, Matthew; Staab, Janet F; Lyman, Courtney A; Gordon, Laura J; Sundstrom, Paula

    2007-12-01

    Candida albicans is an opportunistic human fungal pathogen that causes systemic candidiasis as well as superficial mucosal candidiasis. In response to the host environment, C. albicans transitions between yeast and hyphal forms. In particular, hyphal growth is important in facilitating adhesion and invasion of host tissues, concomitant with the expression of various hypha-specific virulence factors. In previous work, we showed that the cyclic AMP (cAMP) signaling pathway plays a crucial role in morphogenic transitions and virulence of C. albicans by studying genes encoding adenylate cyclase-associated protein (CAP1) and high-affinity phosphodiesterase (PDE2) (Y. S. Bahn, J. Staab, and P. Sundstrom, Mol. Microbiol. 50:391-409, 2003; and Y. S. Bahn and P. Sundstrom, J. Bacteriol. 183:3211-3223, 2001). However, little is known about the downstream targets of the cAMP signaling pathway that are responsible for morphological transitions and the expression of virulence factors. Here, microarrays were probed with RNA from strains with hypoactive (cap1/cap1 null mutant), hyperactive (pde2/pde2 null mutant), and wild-type cAMP signaling pathways to provide insight into the molecular mechanisms of virulence that are regulated by cAMP and that are related to the morphogenesis of C. albicans. Genes controlling metabolic specialization, cell wall structure, ergosterol/lipid biosynthesis, and stress responses were modulated by cAMP during hypha formation. Phenotypic traits predicted to be regulated by cAMP from the profiling results correlated with the relative strengths of the mutants when tested for resistance to azoles and subjected to heat shock stress and oxidative/nitrosative stress. The results from this study provide important insights into the role of the cAMP signaling pathway not only in morphogenic transitions of C. albicans but also for adaptation to stress and for survival during host infections.

  20. Use of chromogenic tube and methyl blue-sabouraud agar for the identification of Candida albicans strains

    OpenAIRE

    Yucesoy, Mine; Esen, Nuran; Yulug, Nuran

    2001-01-01

    This study was performed to investigate the use of chromogenic tube and methyl blue-Sabouraud agar for the presumptive identification of Candida albicans. 124 clinical isolates, including 111 C.albicans and 13 Candida spp strains, which had been identifie

  1. Prevalence of candida albicans in dental plaque and caries lesion of early childhood caries (ECC) according to sampling site

    OpenAIRE

    Ghasempour, Maryam; Sefidgar, Seyed Ali Asghar; Eyzadian, Haniyeh; Gharakhani, Samaneh

    2011-01-01

    Background: Candida albicans may have cariogenic potential but its role in caries etiology has not been established. The aim of this study was to determine candida albicans in supragingival dental plaque and infected dentine of cervical and proximal in early childhood caries (ECC).

  2. Identification and characterization of Cor33p, a novel protein implicated in tolerance towards oxidative stress in Candida albicans.

    Science.gov (United States)

    Sohn, K; Roehm, M; Urban, C; Saunders, N; Rothenstein, D; Lottspeich, F; Schröppel, K; Brunner, H; Rupp, S

    2005-12-01

    We applied two-dimensional gel electrophoresis to identify downstream effectors of CPH1 and EFG1 under hypha-inducing conditions in Candida albicans. Among the proteins that were expressed in wild-type cells but were strongly downregulated in a cph1Delta/efg1Delta double mutant in alpha-minimal essential medium at 37 degrees C, we could identify not-yet-characterized proteins, including Cor33-1p and Cor33-2p. The two proteins are almost identical (97% identity) and represent products of allelic isoforms of the same gene. Cor33p is highly similar to Cip1p from Candida sp. but lacks any significant homology to proteins from Saccharomyces cerevisiae. Strikingly, both proteins share homology with phenylcoumaran benzylic ether reductases and isoflavone reductases from plants. For other hypha-inducing media, like yeast-peptone-dextrose (YPD) plus serum at 37 degrees C, we could not detect any transcription for COR33 in wild-type cells, indicating that Cor33p is not hypha specific. In contrast, we found a strong induction for COR33 when cells were treated with 5 mM hydrogen peroxide. However, under oxidative conditions, transcription of COR33 was not dependent on EFG1, indicating that other regulatory factors are involved. In fact, upregulation depends on CAP1 at least, as transcript levels were clearly reduced in a Deltacap1 mutant strain under oxidative conditions. Unlike in wild-type cells, transcription of COR33 in a tsa1Delta mutant can be induced by treatment with 0.1 mM hydrogen peroxide. This suggests a functional link between COR33 and thiol-specific antioxidant-like proteins that are important in the oxidative-stress response in yeasts. Concordantly, cor33Delta deletion mutants show retarded growth on YPD plates supplemented with hydrogen peroxide, indicating that COR33 in general is implicated in conferring tolerance toward oxidative stress on Candida albicans.

  3. DAYA ANTIMIKROBA EKSTRAK COLEUS AMBOINICUS, LOUR TERHADAP CANDIDA ALBICANS PADA RESIN AKRILIK

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    Devi Rianti

    2015-08-01

    Full Text Available A laboratory experimental study conducted on antimicrobial effects of Coleus amboinicus, Lour concentrate towards Candida albicans on acrylic resin. Samples of this study are 10x10x1 mm heat cured acrylic plates immersed in 15%, 12.5%, 10%, 7.5% of Coleus amboinicus, Lour concentrate solution. Sterilized aquadest was used as control. 16 samples were used for each exercise. Statistical analyses used are One-way Anova and LSD with 5% significance degree. The result showed that increasing Coleus amboinicus, Lour concentrate solution i.e. 7.5%, 10%, 12.5%, 15% will increased the antimicrobial effects towards Candida albicans. The most effective concentrate solution in reducing Candida albicans colonies is 15%.

  4. An Optimized Lock Solution Containing Micafungin, Ethanol and Doxycycline Inhibits Candida albicans and Mixed C. albicans – Staphyloccoccus aureus Biofilms

    Science.gov (United States)

    Lown, Livia; Peters, Brian M.; Walraven, Carla J.; Noverr, Mairi C.; Lee, Samuel A.

    2016-01-01

    Candida albicans is a major cause of catheter-related bloodstream infections and is associated with high morbidity and mortality. Due to the propensity of C. albicans to form drug-resistant biofilms, the current standard of care includes catheter removal; however, reinsertion may be technically challenging or risky. Prolonged exposure of an antifungal lock solution within the catheter in conjunction with systemic therapy has been experimentally attempted for catheter salvage. Previously, we demonstrated excellent in vitro activity of micafungin, ethanol, and high-dose doxycycline as single agents for prevention and treatment of C. albicans biofilms. Thus, we sought to investigate optimal combinations of micafungin, ethanol, and/or doxycycline as a lock solution. We performed two- and three-drug checkerboard assays to determine the in vitro activity of pairwise or three agents in combination for prevention or treatment of C. albicans biofilms. Optimal lock solutions were tested for activity against C. albicans clinical isolates, reference strains and polymicrobial C. albicans-S. aureus biofilms. A solution containing 20% (v/v) ethanol, 0.01565 μg/mL micafungin, and 800 μg/mL doxycycline demonstrated a reduction of 98% metabolic activity and no fungal regrowth when used to prevent fungal biofilm formation; however there was no advantage over 20% ethanol alone. This solution was also successful in inhibiting the regrowth of C. albicans from mature polymicrobial biofilms, although it was not fully bactericidal. Solutions containing 5% ethanol with low concentrations of micafungin and doxycycline demonstrated synergistic activity when used to prevent monomicrobial C. albicans biofilm formation. A combined solution of micafungin, ethanol and doxycycline is highly effective for the prevention of C. albicans biofilm formation but did not demonstrate an advantage over 20% ethanol alone in these studies. PMID:27428310

  5. Analysis of the in vitro adherence of Streptococcus mutans and Candida albicans Análise da aderência in vitro de Streptococcus mutans e Candida albicans

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    Dicler de Sant'Anna Vitor Barbieri

    2007-12-01

    Full Text Available The objective of the present study was to investigate the in vitro adherence capacity of Streptococcus mutans and Candida albicans. Adherence assays were conducted on dental surfaces and analyzed by scanning electron microscopy (SEM. Extracted human teeth were inoculated with Streptococcus mutans or Candida albicans and with both species simultaneously, and incubated at 37ºC for 21 days. Bacterial inocula had been obtained from saliva samples of children that had been colonized by both organisms. ATCC reference strains were used as controls. SEM analyses showed that the biofilm that covered the entire analyzed dental surface was more homogeneous inoculated with the two microorganisms simultaneously than with each species separately. In a second experiment, carried out with isolates that had shown the highest adherence the isolates were tested for adherence to high-density polyethylene substrates. The potentialization of the adherence capacity of Streptococcus mutans and Candida albicans when in association was confirmed.O objetivo deste trabalho foi investigar a capacidade de aderência in vitro de Streptococcus mutans e Candida albicans. Ensaios de aderência foram realizados in vitro na superfície dentária, com posterior análise por Microscopia Eletrônica de Varredura (M.E.V.. Dentes humanos extraídos foram inoculados com Streptococcus mutans e Candida albicans, além de ambas espécies em conjunto, e foram incubados a 37ºC por 21 dias. Os inóculos eram provenientes de amostras salivares de crianças colonizadas por ambos microrganismos. Como controles foram utilizadas linhagens de referência ATCC dos dois microrganismos. A análise por M.E.V. mostrou a formação de um biofilme que cobriu toda a superfície dentária analisada de forma mais homogênea quando incubados juntos do que separadamente. Um segundo experimento foi desenvolvido utilizando isolados mostrando maior aderência dos experimentos anteriores e cortes de polietileno

  6. 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.

  7. Candida albicans identification: comparison among nine phenotypic systems and a multiplex PCR.

    Science.gov (United States)

    Liguori, G; Di Onofrio, V; Gallé, F; Lucariello, A; Albano, L; Catania, M R; Guida, M

    2010-09-01

    Candida albicans is the most common fungal pathogen isolated from clinical samples and is also the most common yeast species carried as a commensal by healthy individuals although some non-C. albicans species account for an important number of infections. To compare nine phenotypic systems for C. albicans identification [API 20C AUX; RapID Yeast Identification panel (RYIP); Vitek2 ID-YST system; chromogenic media, CHRO-Magar, Oxoid Chromogenic Candida Agar (OCCA), Candida ID2, Candida Identification Agar, CandiSelect 4, and Chromalbicans Agar] with multiplex PCR. A collection of 390 yeast strains was obtained by routine isolation from oral and vaginal swabs. All of the yeasts isolated were tested for germ tube formation, and then submitted to a multiplex PCR protocol tested in previous studies, and to nine phenotypical commercial methods, together with the reference ATCC strains. Comparison was limited to the ability of the tests to identify C. albicans. 253 isolates were provisionally identified as C. albicans by germ tube, and their identities were further confirmed with the multiplex PCR. Sensitivity of phenotypical systems ranged from 81.9% (Vitek2) to 87.7% (Candida ID2 e CHROMagar). For specificity, the highest value was 96.8% for Candida ID2, and the lowest value (75.1%) was for Chromalbicans Agar. Although with differences in discriminatory power, the methods tested showed overall acceptable levels of sensitivity and specificity respect to the multiplex PCR; therefore, all could be useful for C. albicans identification where molecular differentiation is not available.

  8. Candida albicans Heat Shock Proteins and Hsps-Associated Signaling Pathways as Potential Antifungal Targets

    Science.gov (United States)

    Gong, Ying; Li, Tao; Yu, Cuixiang; Sun, Shujuan

    2017-01-01

    In recent decades, the incidence of invasive fungal infections has increased notably. Candida albicans (C. albicans), a common opportunistic fungal pathogen that dwells on human mucosal surfaces, can cause fungal infections, especially in immunocompromised and high-risk surgical patients. In addition, the wide use of antifungal agents has likely contributed to resistance of C. albicans to traditional antifungal drugs, increasing the difficulty of treatment. Thus, it is urgent to identify novel antifungal drugs to cope with C. albicans infections. Heat shock proteins (Hsps) exist in most organisms and are expressed in response to thermal stress. In C. albicans, Hsps control basic physiological activities or virulence via interaction with a variety of diverse regulators of cellular signaling pathways. Moreover, it has been demonstrated that Hsps confer drug resistance to C. albicans. Many studies have shown that disrupting the normal functions of C. albicans Hsps inhibits fungal growth or reverses the tolerance of C. albicans to traditional antifungal drugs. Here, we review known functions of the diverse Hsp family, Hsp-associated intracellular signaling pathways and potential antifungal targets based on these pathways in C. albicans. We hope this review will aid in revealing potential new roles of C. albicans Hsps in addition to canonical heat stress adaptions and provide more insight into identifying potential novel antifungal targets. PMID:29312897

  9. Granulomatous myocarditis caused by Candida albicans in a canary (Serinus canaria).

    Science.gov (United States)

    Marruchella, Giuseppe; Todisco, Gianluca; D'Arezzo, Silvia; Di Guardo, Giovanni; Paglia, Maria Grazia

    2011-09-01

    Candida albicans is among the major agents of mucous membrane mycosis in humans and animals, with systemic and deep infections observed in immunocompromised hosts. We describe a case of fatal granulomatous myocarditis caused by C albicans in a 20-day-old canary (Serinus canaria). The etiologic diagnosis was confirmed by identifying characteristic morphologic features of the organism, combined with histochemical staining, and followed by the use of ad hoc biomolecular analysis.

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

    OpenAIRE

    Leite, Maria Clerya Alvino; Bezerra, André Parente de Brito; de Sousa, Janiere Pereira; Guerra, Felipe Queiroga Sarmento; Lima, Edeltrudes de Oliveira

    2014-01-01

    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-kil...

  11. Identification of a Cell Death Pathway in Candida albicans during the Response to Pheromone ▿ †

    OpenAIRE

    Alby, Kevin; Schaefer, Dana; Sherwood, Racquel Kim; Jones, Stephen K.; Bennett, Richard J.

    2010-01-01

    Mating in hemiascomycete yeasts involves the secretion of pheromones that induce sexual differentiation in cells of the opposite mating type. Studies in Saccharomyces cerevisiae have revealed that a subpopulation of cells experiences cell death during exposure to pheromone. In this work, we tested whether the phenomenon of pheromone-induced death (PID) also occurs in the opportunistic pathogen Candida albicans. Mating in C. albicans is uniquely regulated by white-opaque phenotypic switching; ...

  12. Fluconazole treatment of Candida albicans infection in mice: does in vitro susceptibility predict in vivo response?

    OpenAIRE

    Graybill, J R; Najvar, L K; Holmberg, J D; Correa, A.; Luther, M F

    1995-01-01

    A series of fluconazole-susceptible and-fluconazole resistant Candida albicans fungal isolates were used to infect mice intravenously. Mice were treated with varying doses of fluconazole beginning one day after infection. For all of the 6 fluconazole-susceptible isolates, fluconazole was highly effective at or = 40 mg/kg twice daily in 4 fluconazole-resistant isolates. Although the correlation is not precise, in vitro susceptibility testing of C. albicans can predict in vivo response to fluc...

  13. Mutational analysis of metacaspase CaMca1 and decapping activator Edc3 in the pathogenicity of Candida albicans.

    Science.gov (United States)

    Jeong, Jeong-Hoon; Lee, Seok-Eui; Kim, Jinmi

    2016-12-01

    Candida albicans, an opportunistic fungal pathogen, displays apoptotic cell death in response to various stresses and a wide range of antifungal treatments. CaMca1, which is the only metacaspase in C. albicans, has been described as a key player in apoptotic cell death. Edc3 is an mRNA decapping activator and a scaffold protein of processing bodies. Edc3 was previously shown to regulate CaMCA1 expression and oxidative stress-induced apoptosis. In this study, we analyzed the contribution of the catalytic residues of the CaMca1 to the oxidative stress-induced apoptosis and pathogenicity of C. albicans. The CaMCA1C292A mutation decreased caspase activity to a level similar to that observed in the Camca1/Camca1 deletion strain and over-expression of CaMCA1C292A failed to suppress the oxidative-stress phenotypes of the edc3/edc3 mutant strain. The edc3/edc3, Camca1/Camca1, and CaMCA1C292A mutant strains were not virulent in a murine candidiasis model. Filamentation defects were observed in the Camca1/Camca1 mutant cells, whereas this defect was only partial in CaMCA1C292A mutant cells. These results suggest that CaMca1 and Edc3 play essential roles in the oxidative stress-induced apoptosis and virulence of C. albicans, and also support the notion that Edc3 is a key regulator of CaMca1 expression. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. 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.

  15. Biotyping and genotypic diversity among oral Candida albicans strains from caries-free and caries-active healthy children

    OpenAIRE

    Mardegan,Rita de Cássia; Klein,Marlise Inêz; Golvea,Magda Baglione; Rodrigues,Janaina Aparecida Oliveira; Gonçalves,Reginaldo Bruno; Höfling,José Francisco

    2006-01-01

    Candida albicans oral strains collected from caries-free and caries-active healthy children ranging from 24 to 36 months old, were studied. The aim of the study was to determine proteinase and phospholipase activities produced by Candida albicans in the two groups and to determine the phenotypic diversity of these enzymes based on genetic polymorphism using the AP-PCR method. Strains identified by morphological and fermentation tests as C. albicans were grown in proteinase and phospholipase a...

  16. Activity of Allyl Isothiocyanate and Its Synergy with Fluconazole against Candida albicans Biofilms.

    Science.gov (United States)

    Raut, Jayant Shankar; Bansode, Bhagyashree Shridhar; Jadhav, Ashwini Khanderao; Karuppayil, Sankunny Mohan

    2017-04-28

    Candidiasis involving the biofilms of Candida albicans is a threat to immunocompromised patients. Candida biofilms are intrinsically resistant to the antifungal drugs and hence novel treatment strategies are desired. The study intended to evaluate the anti-Candida activity of allyl isothiocyanate (AITC) alone and with fluconazole (FLC), particularly against the biofilms. Results revealed the concentration-dependent activity of AITC against the planktonic growth and virulence factors of C. albicans. Significant (p biofilms was evident at biofilm formation. Similarly, the preformed biofilms were significantly (p biofilm formation and the preformed biofilms. No hemolytic activity at the biofilm inhibitory concentrations of AITC and the AITC-FLC combination suggested the absence of cytotoxic effects. The recognizable synergy between AITC and FLC offers a potential therapeutic strategy against biofilm-associated Candida infections.

  17. Boric Acid and Commercial Organoboron Products as Inhibitors of Drug-Resistant Candida albicans.

    Science.gov (United States)

    Larsen, Bryan; Petrovic, Marija; De Seta, Francesco

    2017-10-09

    Clinical use of boric acid as a topical antifungal in women who have failed standard antifungal therapy with azole drugs has been used sporadically for decades. Our previous in vitro work showing inhibition of Candida albicans growth was conducted on clinical isolates without antifungal drug susceptibility profiling. Here, we report that boric acid restricts growth of drug-resistant Candida albicans and inhibits hyphal growth and diminishes cell volume. The availability of over-the-counter organoboron compounds intended for use as oral nutritional supplements led us to determine if these also were inhibitory toward resistant Candida and show here that they also possess antifungal activity. Candida glabrata was also found to be inhibited by boric acid and organoboron compounds. Further development of organoboron compounds as topical therapeutics is of potential value.

  18. Protein phosphatase CaPpz1 is involved in cation homeostasis, cell wall integrity and virulence of Candida albicans.

    Science.gov (United States)

    Adám, Csaba; Erdei, Eva; Casado, Carlos; Kovács, László; González, Asier; Majoros, László; Petrényi, Katalin; Bagossi, Péter; Farkas, Ilona; Molnar, Monika; Pócsi, István; Ariño, Joaquín; Dombrádi, Viktor

    2012-05-01

    The opportunistic pathogen Candida albicans has a single protein phosphatase Z (PPZ) candidate gene termed CaPPZ1, which shows significant allele variability. We demonstrate here that bacterially expressed CaPpz1 protein exhibits phosphatase activity which can be inhibited by recombinant Hal3, a known inhibitor of Saccharomyces cerevisiae Ppz1. Site-directed mutagenesis experiments based on natural polymorphisms allowed the identification of three amino acid residues that affect enzyme activity or stability. The expression of CaPPZ1 in ppz1 S. cerevisiae and pzh1 Schizosaccharomyces pombe cells partially rescued the salt and caffeine phenotypes of the deletion mutants. CaPpz1 also complemented the slt2 S. cerevisiae mutant, which is crippled in the mitogen-activated protein (MAP) kinase that mediates the cell wall integrity signalling pathway. Collectively, our results suggest that the orthologous PPZ enzymes have similar but not identical functions in different fungi. The deletion of the CaPPZ1 gene in C. albicans resulted in a mutant that was sensitive to salts such as LiCl and KCl, to caffeine, and to agents that affect cell wall biogenesis such as Calcofluor White and Congo red, but was tolerant to spermine and hygromycin B. Reintegration of the CaPPZ1 gene into the deletion mutant alleviated all of the mutant phenotypes tested. Thus CaPpz1 is involved in cation homeostasis, cell wall integrity and the regulation of the membrane potential of C. albicans. In addition, the germ tube growth rate, and virulence in the BALB/c mouse model, were reduced in the null mutant, suggesting a novel function for CaPpz1 in the yeast to hypha transition that may have medical relevance.

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

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    Horvath Lynn L

    2006-01-01

    Full Text Available Abstract Background CHROMagar Candida (CaC is increasingly being reported as a medium used to differentiate Candida albicans from non-albicans Candida (NAC species. Rapid identification of NAC can assist the clinician in selecting appropriate antifungal therapy. CaC is a differential chromogenic medium designed to identify C. albicans, C. krusei, and C. tropicalis based on colony color and morphology. Some reports have proposed that CaC can also reliably identify C. dubliniensis and C. glabrata. Methods We evaluated the usefulness of CaC in the identification of C. dubliniensis, C. famata, C. firmetaria, C. glabrata, C. guilliermondii, C. inconspicua, C. kefyr, C. lipolytica, C. lusitaniae, C. norvegensis, C. parapsilosis, and C. rugosa. Results Most NAC produced colonies that were shades of pink, lavender, or ivory. Several isolates of C. firmetaria and all C. inconspicua produced colonies difficult to differentiate from C. krusei. Most C. rugosa isolates produced unique colonies with morphology like C. krusei except in a light blue-green color. C. glabrata isolates produced small dark violet colonies that could be differentiated from the pink and lavender colors produced by other species. All seventeen isolates of C. dubliniensis produced green colonies similar to those produced by C. albicans. Conclusion C. glabrata and C. rugosa appear distinguishable from other species using CaC. Some NAC, including C. firmetaria and C. inconspicua, could be confused with C. krusei using this medium.

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

    Science.gov (United States)

    Hospenthal, Duane R; Beckius, Miriam L; Floyd, Karon L; Horvath, Lynn L; Murray, Clinton K

    2006-01-03

    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. 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. 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. 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.

  1. Role of Non Albicans Candida Spp. and Biofilm in Neonatal ICU.

    Science.gov (United States)

    Goel, Shagun; Mittal, Seema; Chaudhary, Uma

    2016-01-01

    Candida spp. remains the fungal species most commonly associated with biofilm formation. Increase in Candida infections in last decades has almost paralleled the increase and wide spread use of a broad range of medical implant devices mainly in population with impaired host defences. One of the most important characteristics of biofilms is their high level of resistance to antimicrobial drugs. This study was conducted to know the prevalence of different Candida spp. causing blood stream infections and ability to form biofilm and to evaluate the co relation of biofilm with antifungal drug resistance. The present study was conducted on 12464 blood samples for the identification and speciation of various Candida spp. causing blood stream infection over a period of one year. Antifungal susceptibility was performed as per clinical laboratory standard institute guidelines and biofilm formation was detected by method described by Christensen's et al. Out of total 12464 blood culture received, 1378 (11.05%) were culture positive rest and among culture positive 100 (7.25%) Candida isolates were recovered. C. tropicalis was the commonest (43%) species followed by C. albicans (41%), C. krusei (9%) and C. parapsilosis (7%). A total of 41 Candida isolates were biofilm producers and rest 59 isolates were non-biofilm producers. A changing trend of increased prevalence of non albicans Candida spp. was observed which were resistant to commonly used antifungal fluconazole. Multi drug resistance was more common in biofilm forming Candida isolates.

  2. 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 terpenoids resulted in significant (p 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.

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

    Science.gov (United States)

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

    2013-03-10

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

  4. A novel role for the transcription factor Cwt1p as a negative regulator of nitrosative stress in Candida albicans.

    Directory of Open Access Journals (Sweden)

    Adnane Sellam

    Full Text Available The ability of Candida albicans to survive in the presence of nitrosative stress during the initial contact with the host immune system is crucial for its ability to colonize mammalian hosts. Thus, this fungus must activate robust mechanisms to neutralize and repair nitrosative-induced damage. Until now, very little was known regarding the regulatory circuits associated with reactive nitrogen species detoxification in fungi. To gain insight into the transcriptional regulatory networks controlling nitrosative stress response (NRS in C. albicans a compilation of transcriptional regulator-defective mutants were screened. This led to the identification of Cwt1p as a negative regulator of NSR. By combining genome-wide location and expression analyses, we have characterized the Cwt1p regulon and demonstrated that Cwt1p is directly required for proper repression of the flavohemoglobin Yhb1p, a key NO-detoxification enzyme. Furthermore, Cwt1p operates both by activating and repressing genes of specific functions solicited upon NSR. Additionally, we used Gene Set Enrichment Analysis to reinvestigate the C. albicans NSR-transcriptome and demonstrate a significant similarity with the transcriptional profiles of C. albicans interacting with phagocytic host-cells. In summary, we have characterized a novel negative regulator of NSR and bring new insights into the transcriptional regulatory network governing fungal NSR.

  5. 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.

  6. Candida albicans and Candida parapsilosis rapidly up-regulate galectin-3 secretion by human gingival epithelial cells.

    Science.gov (United States)

    Tamai, Riyoko; Kiyoura, Yusuke

    2014-02-01

    Galectin-3 is a β-galactoside-binding C-type lectin that plays an important role in innate immunity. The purpose of this study was to determine whether Candida albicans and Candida parapsilosis up-regulate galectin-3 secretion by human gingival epithelial cells and gingival fibroblasts. Ca9-22, a human gingival epithelial cell line, and human gingival fibroblasts were incubated in the presence or absence of C. albicans or C. parapsilosis without serum. Levels of secreted human galectin-3 in culture supernatants were measured by enzyme-linked immunosorbent assay. We also pretreated Ca9-22 cells with cytochalasin D (an actin polymerization inhibitor), ALLN (a calpain inhibitor) and LY294002 [a phosphatidylinositol-3 kinase (PI3K) inhibitor] to determine whether the up-regulation of galectin-3 secretion was mediated by cytoskeletal changes, protease activity, or PI3K signaling. Galectin-3 secretion was significantly and rapidly up-regulated by live C. albicans and C. parapsilosis, as well as heat-killed C. albicans. In addition, cytochalasin D, LY294002 and ALLN did not inhibit the up-regulation in galectin-3 secretion. These results suggest that both live and heat-killed C. albicans and C. parapsilosis may increase the activity of the innate immune system and invasion by other microorganisms via up-regulation of galectin-3 secretion.

  7. Production of carcinogenic acetaldehyde by Candida albicans from patients with potentially malignant oral mucosal disorders.

    Science.gov (United States)

    Gainza-Cirauqui, M L; Nieminen, M T; Novak Frazer, L; Aguirre-Urizar, J M; Moragues, M D; Rautemaa, R

    2013-03-01

    Production of carcinogenic acetaldehyde by Candida has been suggested to contribute to epithelial dysplasia and oral carcinogenesis. Oral lichen planus (OLP), oral lichenoid lesion (OLL) and oral leukoplakia (OL) are potentially carcinogenic oral diseases where colonisation by Candida is common, but acetaldehyde production by Candida has not been studied. Acetaldehyde production in ethanol (11 mM), glucose (100 mM), ethanol-glucose (11 mM and 100 mM) or red wine (1200 mM ethanol) incubation by Candida albicans from patients with OLL (n = 6), OLP (n = 16), OL (n = 6) and controls (n = 6) was measured by gas chromatography. Participants completed a questionnaire regarding their smoking habits and alcohol consumption. All Candida albicans isolates produced potentially carcinogenic levels of acetaldehyde (>100 μM) in all incubations containing ethanol. The control group isolates produced the highest acetaldehyde levels. Isolates from smokers produced more acetaldehyde in all incubations than those from non-smokers. The difference was significant in ethanol-glucose incubation. Isolates from patients who were both smokers and drinkers produced the highest amounts when incubated in ethanol, ethanol-glucose and wine. Candida albicans isolated from potentially carcinogenic oral diseases can produce mutagenic amounts of acetaldehyde. Cigarette smoking and alcohol consumption may favour adaptational changes resulting in the upregulation of candidal acetaldehyde metabolism. © 2012 John Wiley & Sons A/S. All rights reserved.

  8. Application of the systematic "DAmP" approach to create a partially defective C. albicans mutant.

    Science.gov (United States)

    Finkel, J S; Yudanin, N; Nett, J E; Andes, D R; Mitchell, A P

    2011-11-01

    An understanding of gene function often relies upon creating multiple kinds of alleles. Functional analysis in Candida albicans, a major fungal pathogen, has generally included characterization of mutant strains with insertion or deletion alleles and over-expression alleles. Here we use in C. albicans another type of allele that has been employed effectively in the model yeast Saccharomyces cerevisiae, a "Decreased Abundance by mRNA Perturbation" (DAmP) allele (Yan et al., 2008). DAmP alleles are created systematically through replacement of 30 noncoding regions with nonfunctional heterologous sequences, and thus are broadly applicable. We used a DAmP allele to probe the function of Sun41, a surface protein with roles in cell wall integrity, cell-cell adherence, hyphal formation, and biofilm formation that has been suggested as a possible therapeutic target (Firon et al., 2007; Hiller et al., 2007; Norice et al., 2007). A SUN41-DAmP allele results in approximately 10-fold reduced levels of SUN41 RNA, and yields intermediate phenotypes in most assays. We report that a sun41Δ/Δ mutant is defective in biofilm formation in vivo, and that the SUN41-DAmP allele complements that defect. This finding argues that Sun41 may not be an ideal therapeutic target for biofilm inhibition, since a 90% decrease in activity has little effect on biofilm formation in vivo. We anticipate that DAmP alleles of C. albicans genes will be informative for analysis of other prospective drug targets, including essential genes.

  9. Candida albicans orf19.3727 encodes phytase activity and is essential for human tissue damage.

    Directory of Open Access Journals (Sweden)

    Paul Wai-Kei Tsang

    Full Text Available Candida albicans is a clinically important human fungal pathogen. We previously identified the presence of cell-associated phytase activity in C. albicans. Here, we reveal for the first time, that orf19.3727 contributes to phytase activity in C. albicans and ultimately to its virulence potency. Compared with its wild type counterpart, disruption of C. albicans orf19.3727 led to decreased phytase activity, reduced ability to form hyphae, attenuated in vitro adhesion, and reduced ability to penetrate human epithelium, which are the major virulence attributes of this yeast. Thus, orf19.3727 of C. albicans plays a key role in fungal pathogenesis. Further, our data uncover a putative novel strategy for anti-Candidal drug design through inhibition of phytase activity of this common pathogen.

  10. Anti-fungal activity of Morinda citrifolia (noni) extracts against Candida albicans: an in vitro study.

    Science.gov (United States)

    Barani, K; Manipal, Sunayana; Prabu, D; Ahmed, Adil; Adusumilli, Preethi; Jeevika, C

    2014-01-01

    The aim of this study was to investigate the anti-fungal activity of Morinda citrifolia fruit extract on Candida albicans. 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. 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. M. citrifolia fruit extract had an anti-fungal effect on C. albicans and the inhibitory effect varied with concentration.

  11. 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.

  12. Development and regulation of single- and multi-species Candida albicans biofilms

    Science.gov (United States)

    Lohse, Matthew B.; Gulati, Megha; Johnson, Alexander D.; Nobile, Clarissa J.

    2017-01-01

    Candida albicans is among the most prevalent fungal species of the human microbiota and asymptomatically colonizes healthy individuals. However, it is also an opportunistic pathogen that can cause severe, and often fatal, bloodstream infections. The medical impact of C. albicans typically depends on its ability to form biofilms, which are closely packed communities of cells that attach to surfaces, such as tissues and implanted medical devices. In this Review, we provide an overview of the processes involved in the formation of C. albicans biofilms and discuss the core transcriptional network that regulates biofilm development. We also consider some of the advantages that biofilms provide to C. albicans in comparison with planktonic growth and explore polymicrobial biofilms that are formed by C. albicans and certain bacterial species. PMID:29062072

  13. Effect of jujube honey on Candida albicans growth and biofilm formation.

    Science.gov (United States)

    Ansari, Mohammad Javed; Al-Ghamdi, Ahmad; Usmani, Salma; Al-Waili, Noori S; Sharma, Deepak; Nuru, Adgaba; Al-Attal, Yehya

    2013-07-01

    Candida species, especially Candida albicans, are major fungal pathogens of humans that are capable of causing superficial mucosal infections and systemic infections in humans. The aim of this study was to evaluate the jujube (Zizyphus spina-christi) honey for its in vitro inhibitory activity against pre-formed biofilm and its interference with the biofilm formation of C. albicans. The XTT reduction assay, scanning electron microscopy (SEM) and atomic force microscopy (AFM) were employed to determine the inhibitory effect of Jujube honey on C. albicans biofilm. Changes in the infrared spectrum after treatment with honey were also determined by Fourier transform infrared (FTIR) spectroscopy. Jujube honey affects biofilms by decreasing the size of mature biofilms and by disruption of their structure. At a concentration of 40% w/v, it interferes with formation of C. albicans biofilms and disrupts established biofilms. The SEM and AFM results indicated that this type of honey affected the cellular morphology of C. albicans and decreased biofilm thickness. The present findings show that jujube honey has antifungal properties against C. albicans and has the ability to inhibit the formation of C. albicans biofilms and disrupt established biofilms. Copyright © 2013 IMSS. Published by Elsevier Inc. All rights reserved.

  14. 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. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. Antifungal activity of Piper aduncum and Peperomia pellucida leaf ethanol extract against Candida albicans

    Science.gov (United States)

    Hastuti, Utami Sri; Ummah, Yunita Putri Irsadul; Khasanah, Henny Nurul

    2017-05-01

    This research was done to 1) examine the effect of Piper aduncum leaf ethanol extract at certain concentrations against Candida albicans colony growth inhibition in vitro; 2) examine the effect of Peperomia pellucida leaf ethanol extract at certain concentrations toward Candida albicans colony growth inhibition in vitro; and 3) determine the most effective concentration of P. aduncum and P. pellucida leaves ethanol extract against C. albicans colony growth inhibition in vitro. These plant extracts were prepared by the maceration technique using 95% ethanol, and then sterile filtered and evaporated to obtain the filtrate. The filtrate was diluted with sterile distilled water at certain concentrations, i.e.: 0%, 10%, 20%, 30%, 405, 50%, 60%, 70%, 80%, and 90%. The antifungal effect of each leaf extract concentration was examined by the agar diffusion method on Sabouraud Dextrose Agar medium. The research results are: 1) the P.aduncum leaf ethanol extract at some concentrations has an effect against C. albicans colony growth inhibition in vitro; 2) the P.pellucida leaf ethanol extract at some concentrations has an effect against C. albicans colony growth inhibition in vitro; 3) the P. aduncum leaf ethanol extract at 80% is the most effective for C. albicans colony growth inhibition in vitro; and 4) the P. pellucida leaf ethanol extract at 70% is the most effective for C. albicans colony growth inhibition in vitro.

  16. Activation of HIF-1α and LL-37 by commensal bacteria inhibits Candida albicans colonization.

    Science.gov (United States)

    Fan, Di; Coughlin, Laura A; Neubauer, Megan M; Kim, Jiwoong; Kim, Min Soo; Zhan, Xiaowei; Simms-Waldrip, Tiffany R; Xie, Yang; Hooper, Lora V; Koh, Andrew Y

    2015-07-01

    Candida albicans colonization is required for invasive disease. Unlike humans, adult mice with mature intact gut microbiota are resistant to C. albicans gastrointestinal (GI) colonization, but the factors that promote C. albicans colonization resistance are unknown. Here we demonstrate that commensal anaerobic bacteria-specifically clostridial Firmicutes (clusters IV and XIVa) and Bacteroidetes-are critical for maintaining C. albicans colonization resistance in mice. Using Bacteroides thetaiotamicron as a model organism, we find that hypoxia-inducible factor-1α (HIF-1α), a transcription factor important for activating innate immune effectors, and the antimicrobial peptide LL-37 (CRAMP in mice) are key determinants of C. albicans colonization resistance. Although antibiotic treatment enables C. albicans colonization, pharmacologic activation of colonic Hif1a induces CRAMP expression and results in a significant reduction of C. albicans GI colonization and a 50% decrease in mortality from invasive disease. In the setting of antibiotics, Hif1a and Camp (which encodes CRAMP) are required for B. thetaiotamicron-induced protection against C. albicans colonization of the gut. Thus, modulating C. albicans GI colonization by activation of gut mucosal immune effectors may represent a novel therapeutic approach for preventing invasive fungal disease in humans.

  17. Liposomal thymoquinone effectively combats fluconazole-resistant Candida albicans in a murine model.

    Science.gov (United States)

    Khan, Masood Alam; Aljarbou, Ahmad N; Khan, Arif; Younus, Hina

    2015-05-01

    The aim of the present study was to develop a novel liposomal formulation of thymoquinone (TQ) to treat fluconazole-susceptible and -resistant Candida albicans (C. albicans) infections. The liposomal preparation of TQ (Lip-TQ) was used against a fluconazole-susceptible or -resistant isolate of C. albicans. Various doses of fluconazole (0, 5, 10, 20 and 40 mg/kg) or free TQ or Lip-TQ (0, 1, 2 and 5mg/kg) were used to treat C. albicans infected mice. Mice were observed for 40 days post C. albicans infection, and their kidneys were assessed for the fungal load. Fluconazole showed anti-fungal activity against the drug-susceptible, but not against the -resistant isolate of C. albicans. Free TQ showed its activity against both fluconazole-susceptible or -resistant C. albicans, however, Lip-TQ was found to be the most effective and imparted ∼ 100% and ∼ 90% survival of mice infected with fluconazole-susceptible and -resistant isolates of C. albicans, respectively. Mice treated with Lip-TQ showed highly reduced severity of infection in their tissue homogenates. Therefore, Lip-TQ may effectively be used in the treatment of C. albicans infections, including those which are not responding to fluconazole. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    African Journals Online (AJOL)

    Our results showed that oral C. albicans strains were able to adhere to epithelial cell lines and biomaterials with different degree. In fact, more than 61% of the tested strains were adhesive to Hep-2 and 83% to Caco-2 cells. Strong slime production after safranin stain was found in 40% of strains. Slime producer C. albicans ...

  20. Sensitivity pattern of clinical isolates of Candida albicans from hiv ...

    African Journals Online (AJOL)

    This study was carried out to investigate the sensitivity pattern of clinical isolates of C. albicans from HIV/AIDS patients to combined P. grisea extract and tioconazole. Twenty isolates of C. albicans were obtained from high vaginal swab (HVS) from HIV/AIDS patients in Bishop Shanahan Hospital, Nsukka after their ...

  1. Evaluation of Candida Albicans Biofilm Formation on Various Parts ...

    African Journals Online (AJOL)

    ... non-biological surfaces, such as dental materials. C. albicans adhesion to denture materials is widely recognized as the main reason for the development of stomatitis. This study compared the susceptibility of different parts of the implant system with C. albicans adhesion. Material and Methods: Each material maintained ...

  2. Candida albicans Vrp1 is required for polarized morphogenesis and interacts with Wal1 and Myo5.

    Science.gov (United States)

    Borth, Nicole; Walther, Andrea; Reijnst, Patrick; Jorde, Sigyn; Schaub, Yvonne; Wendland, Jürgen

    2010-10-01

    Recently, a link between endocytosis and hyphal morphogenesis has been identified in Candida albicans via the Wiskott-Aldrich syndrome gene homologue WAL1. To get a more detailed mechanistic understanding of this link we have investigated a potentially conserved interaction between Wal1 and the C. albicans WASP-interacting protein (WIP) homologue encoded by VRP1. Deletion of both alleles of VRP1 results in strong hyphal growth defects under serum inducing conditions but filamentation can be observed on Spider medium. Mutant vrp1 cells show a delay in endocytosis - measured as the uptake and delivery of the lipophilic dye FM4-64 into small endocytic vesicles - compared to the wild-type. Vacuolar morphology was found to be fragmented in a subset of cells and the cortical actin cytoskeleton was depolarized in vrp1 daughter cells. The morphology of the vrp1 null mutant could be complemented by reintegration of the wild-type VRP1 gene at the BUD3 locus. Using the yeast two-hybrid system we could demonstrate an interaction between the C-terminal part of Vrp1 and the N-terminal part of Wal1, which contains the WH1 domain. Furthermore, we found that Myo5 has several potential interaction sites on Vrp1. This suggests that a Wal1-Vrp1-Myo5 complex plays an important role in endocytosis and the polarized localization of the cortical actin cytoskeleton to promote polarized hyphal growth in C. albicans.

  3. Als3 is a Candida albicans invasin that binds to cadherins and induces endocytosis by host cells.

    Science.gov (United States)

    Phan, Quynh T; Myers, Carter L; Fu, Yue; Sheppard, Donald C; Yeaman, Michael R; Welch, William H; Ibrahim, Ashraf S; Edwards, John E; Filler, Scott G

    2007-03-01

    Candida albicans is the most common cause of hematogenously disseminated and oropharyngeal candidiasis. Both of these diseases are characterized by fungal invasion of host cells. Previously, we have found that C. albicans hyphae invade endothelial cells and oral epithelial cells in vitro by inducing their own endocytosis. Therefore, we set out to identify the fungal surface protein and host cell receptors that mediate this process. We found that the C. albicans Als3 is required for the organism to be endocytosed by human umbilical vein endothelial cells and two different human oral epithelial lines. Affinity purification experiments with wild-type and an als3delta/als3delta mutant strain of C. albicans demonstrated that Als3 was required for C. albicans to bind to multiple host cell surface proteins, including N-cadherin on endothelial cells and E-cadherin on oral epithelial cells. Furthermore, latex beads coated with the recombinant N-terminal portion of Als3 were endocytosed by Chinese hamster ovary cells expressing human N-cadherin or E-cadherin, whereas control beads coated with bovine serum albumin were not. Molecular modeling of the interactions of the N-terminal region of Als3 with the ectodomains of N-cadherin and E-cadherin indicated that the binding parameters of Als3 to either cadherin are similar to those of cadherin-cadherin binding. Therefore, Als3 is a fungal invasin that mimics host cell cadherins and induces endocytosis by binding to N-cadherin on endothelial cells and E-cadherin on oral epithelial cells. These results uncover the first known fungal invasin and provide evidence that C. albicans Als3 is a molecular mimic of human cadherins.

  4. Als3 is a Candida albicans invasin that binds to cadherins and induces endocytosis by host cells.

    Directory of Open Access Journals (Sweden)

    Quynh T Phan

    2007-03-01

    Full Text Available Candida albicans is the most common cause of hematogenously disseminated and oropharyngeal candidiasis. Both of these diseases are characterized by fungal invasion of host cells. Previously, we have found that C. albicans hyphae invade endothelial cells and oral epithelial cells in vitro by inducing their own endocytosis. Therefore, we set out to identify the fungal surface protein and host cell receptors that mediate this process. We found that the C. albicans Als3 is required for the organism to be endocytosed by human umbilical vein endothelial cells and two different human oral epithelial lines. Affinity purification experiments with wild-type and an als3delta/als3delta mutant strain of C. albicans demonstrated that Als3 was required for C. albicans to bind to multiple host cell surface proteins, including N-cadherin on endothelial cells and E-cadherin on oral epithelial cells. Furthermore, latex beads coated with the recombinant N-terminal portion of Als3 were endocytosed by Chinese hamster ovary cells expressing human N-cadherin or E-cadherin, whereas control beads coated with bovine serum albumin were not. Molecular modeling of the interactions of the N-terminal region of Als3 with the ectodomains of N-cadherin and E-cadherin indicated that the binding parameters of Als3 to either cadherin are similar to those of cadherin-cadherin binding. Therefore, Als3 is a fungal invasin that mimics host cell cadherins and induces endocytosis by binding to N-cadherin on endothelial cells and E-cadherin on oral epithelial cells. These results uncover the first known fungal invasin and provide evidence that C. albicans Als3 is a molecular mimic of human cadherins.

  5. Candida albicans Airway Colonization Facilitates Subsequent Acinetobacter baumannii Pneumonia in a Rat Model.

    Science.gov (United States)

    Tan, Xiaojiang; Chen, Ruilan; Zhu, Song; Wang, Huijun; Yan, Dongxing; Zhang, Xiangdong; Farmakiotis, Dimitrios; Mylonakis, Eleftherios

    2016-06-01

    The objective of the study was to determine the effects of Candida albicans respiratory tract colonization on Acinetobacter baumannii pneumonia in a rat model. Rats were colonized with C. albicans by instillation of 3 × 10(6) CFU into their airways, while sterile saline was instilled in the control group. The colonized rats were further divided into two groups: treated with amphotericin B or not. The rats were subsequently infected with A. baumannii (10(8) CFU by tracheobronchial instillation). A. baumannii lung CFU counts, cytokine lung levels, and rates of A. baumannii pneumonia were compared between groups. In vitro expression of A. baumannii virulence genes was measured by reverse transcription (RT)-PCR after 24-hour incubation with C. albicans or with Mueller-Hinton (MH) broth alone. Rats with Candida colonization developed A. baumannii pneumonia more frequently and had higher A. baumannii CFU burdens and heavier lungs than controls. After A. baumannii infection, lung interleukin 17 (IL-17) concentrations were lower and gamma interferon (IFN-γ) concentrations were higher in Candida-colonized rats than in controls. Candida-colonized rats treated with amphotericin B had a decreased rate of A. baumannii pneumonia and lower IFN-γ levels but higher IL-17 levels than untreated rats. Expression of basC, barB, bauA, ptk, plc2, and pld2 was induced while expression of ompA and abaI was suppressed in A. baumannii cultured in the presence of C. albicans C. albicans colonization facilitated the development of A. baumannii pneumonia in a rat model. Among Candida-colonized rats, antifungal treatment lowered the incidence of A. baumannii pneumonia. These findings could be due to modification of the host immune response and/or expression of A. baumannii virulence genes by Candida spp. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  6. Variation in Candida albicans EFG1 expression enables host-dependent changes in colonizing fungal populations.

    Science.gov (United States)

    Pierce, Jessica V; Kumamoto, Carol A

    2012-01-01

    To understand differences in host-Candida albicans interactions that occur during colonization of healthy or compromised hosts, production of phenotypic variants and colonization of healthy or immunodeficient mice by C. albicans were studied. We showed that activity of the transcription factor Efg1p exhibited cell-to-cell variability and identified Efg1p as a major regulator of colonization. In C. albicans populations colonizing the murine gastrointestinal tract, average expression of EFG1 differed depending on the immune status of the host. We propose that cellular heterogeneity in Efg1p activity allows the C. albicans colonizing population to differ depending on the immune status of the host, because selective pressure from a healthy host alters the composition of the population. These data are the first demonstration that differences in host immune status are associated with differences in gene expression in colonizing C. albicans cells. Altered gene expression in organisms colonizing immunocompromised hosts may begin the transition of C. albicans from a commensal to a pathogen. In healthy people, the fungus Candida albicans colonizes the gastrointestinal tract and other sites without producing obvious pathology. In an immunocompromised patient, the organism can cause serious disease. The demonstration that the expression and activity of the C. albicans transcription factor Efg1p differs during colonization of healthy or immunocompromised mice shows that the organism adjusts its physiology when colonizing different hosts. Further, the effects of a healthy host on a heterogeneous C. albicans population containing cells with different levels of Efg1p activity show that selective pressure in the host can change the makeup of the population, allowing the population to respond to host immune status. The ability to sense host status may be key to the ability of C. albicans to colonize as a harmless commensal in some hosts but become a deadly pathogen in others.

  7. Performance do meio cromogênico Albicans ID2Ò para a rápida identificação de Candida albicans

    OpenAIRE

    Patricio Godoy-Martínez; Azevedo,Ana C.; Viviane Reis; Thelma Alves; Almeida, Leila P.; Colombo, Arnaldo L.

    2006-01-01

    The aim of our study was to evaluate the accuracy of the chromogenic media Albicans ID2Ò (bioMérieux, France) for the identification of Candida albicans among 330 yeast strains. All C. albicans (100) and C. dubliniensis (20) strains exhibited blue color when cultured on Albicans ID2Ò. However, the blue color was also exhibited by cultures of C. rugosa (30/30) and C. tropicalis (3/50) isolates.O objetivo do nosso estudo foi avaliar a eficácia do meio cromogênico Albicans ID2Ò (bioMérieux, Fran...

  8. The effectiveness of Nigella sativa seed extract in inhibiting Candida albicans on heat cured acrylic resin

    Directory of Open Access Journals (Sweden)

    Hanoem EH

    2011-09-01

    Full Text Available Background: Indonesia has a variety of plants that can be used for medicines. One of the medicinal plants is Nigella sativa. Nigella sativa has been used for medicinal purposes, both as medicinal herb and as medicinal oil. It contains saponin and atsiri oils that have antifungal, antimicrobial and antibacterial effects. Nigella sativa has been suggested as denture cleansers since it can inhibit the growth of Candida albicans (C. albicans on heat cured acrylic resin. Purpose: The aim of this research is to know the effectiveness of Nigella sativa seed extract in inhibiting the growth of C. albicans on heat cured acrylic resin. Methods: Eighteen acrylic samples were divided into three groups. Group I was control group, only contaminated with C. albicans without immersing in any solution. Group II was acrylic sample immersed in sterile aquades for one hour. Group III was acrylic sample immersed in Nigella sativa seed extract for one hour. Results: There were significant differences of C. albicans (p < 0.05 among the three groups. The number of Candida albicans was significantly higher in Group I, while that in group II was lower than that in group I, and that in group III was the lowest. Conclusion: Nigella sativa seed extract was effective in inhibiting the growth of C. albicans on heat cured acrylic resin.Latar belakang: Indonesia memiliki berbagai tanaman yang dapat dipakai sebagai obat, salah satu tanaman tersebut adalah jinten hitam (Nigella sativa. Pada beberapa negara jinten hitam telah digunakan untuk berbagai tujuan, baik sebagai obat herbal maupun sebagai minyak. kandungan jinten hitam adalah saponin dan minyak atsiri yang mempunyai efek anti jamur dan anti mikroba. Jinten hitam disarankan sebagai pilihan pembersih gigi tiruan yang dapat menghambat pertumbuhan Candida albicans (C. albicans pada resin akrilik heat cured. Tujuan: Tujuan penelitian ini adalah mengetahui efektivitas dari ekstrak biji jinten hitam dalam menghambat pertumbuhan

  9. 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. Copyright © 2015 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

  10. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. 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.)

  12. Candida albicans shaving to profile human serum proteins on hyphal surface

    Directory of Open Access Journals (Sweden)

    Elvira eMarin

    2015-12-01

    Full Text Available Candida albicans is a human opportunistic fungus and it is responsible for a wide variety of infections, either superficial or systemic. C. albicans is a polymorphic fungus and its ability to switch between yeast and hyphae is essential for its virulence. Once C. albicans obtains access to the human body, the host serum constitutes a complex environment of interaction with C. albicans cell surface in bloodstream. To draw a comprehensive picture of this relevant step in host-pathogen interaction during invasive candidiasis, we have optimized a gel-free shaving proteomic strategy to identify both, human serum proteins coating C. albicans cells and fungi surface proteins simultaneously. This approach was carried out with normal serum (NS and heat inactivated serum (HIS. We identified 214 human and 372 C. albicans unique proteins. Proteins identified in C. albicans included 147 which were described as located at the cell surface and 52 that were described as immunogenic. Interestingly, among these C. albicans proteins, we identified 23 GPI-anchored proteins, Gpd2 and Pra1, which are involved in complement system evasion and 7 other proteins that are able to attach plasminogen to C. albicans surface (Adh1, Eno1, Fba1, Pgk1, Tdh3, Tef1 and Tsa1. Furthermore, 12 proteins identified at the C. albicans hyphae surface induced with 10% human serum were not detected in other hypha-induced conditions. The most abundant human proteins identified are involved in complement and coagulation pathways. Remarkably, with this strategy, all main proteins belonging to complement cascades were identified on the C. albicans surface. Moreover, we identified immunoglobulins, cytoskeletal proteins, metabolic proteins such as apolipoproteins and others. Additionally, we identified more inhibitors of complement and coagulation pathways, some of them serpin proteins (serine protease inhibitors, in HIS versus NS. On the other hand, we detected a higher amount of C3 at the C

  13. Secretory Aspartyl Proteinases Cause Vaginitis and Can Mediate Vaginitis Caused by Candida albicans in Mice.

    Science.gov (United States)

    Pericolini, Eva; Gabrielli, Elena; Amacker, Mario; Kasper, Lydia; Roselletti, Elena; Luciano, Eugenio; Sabbatini, Samuele; Kaeser, Matthias; Moser, Christian; Hube, Bernhard; Vecchiarelli, Anna; Cassone, Antonio

    2015-06-02

    Vaginal inflammation (vaginitis) is the most common disease caused by the human-pathogenic fungus Candida albicans. Secretory aspartyl proteinases (Sap) are major virulence traits of C. albicans that have been suggested to play a role in vaginitis. To dissect the mechanisms by which Sap play this role, Sap2, a dominantly expressed member of the Sap family and a putative constituent of an anti-Candida vaccine, was used. Injection of full-length Sap2 into the mouse vagina caused local neutrophil influx and accumulation of the inflammasome-dependent interleukin-1β (IL-1β) but not of inflammasome-independent tumor necrosis factor alpha. Sap2 could be replaced by other Sap, while no inflammation was induced by the vaccine antigen, the N-terminal-truncated, enzymatically inactive tSap2. Anti-Sap2 antibodies, in particular Fab from a human combinatorial antibody library, inhibited or abolished the inflammatory response, provided the antibodies were able, like the Sap inhibitor Pepstatin A, to inhibit Sap enzyme activity. The same antibodies and Pepstatin A also inhibited neutrophil influx and cytokine production stimulated by C. albicans intravaginal injection, and a mutant strain lacking SAP1, SAP2, and SAP3 was unable to cause vaginal inflammation. Sap2 induced expression of activated caspase-1 in murine and human vaginal epithelial cells. Caspase-1 inhibition downregulated IL-1β and IL-18 production by vaginal epithelial cells, and blockade of the IL-1β receptor strongly reduced neutrophil influx. Overall, the data suggest that some Sap, particularly Sap2, are proinflammatory proteins in vivo and can mediate the inflammasome-dependent, acute inflammatory response of vaginal epithelial cells to C. albicans. These findings support the notion that vaccine-induced or passively administered anti-Sap antibodies could contribute to control vaginitis. Candidal vaginitis is an acute inflammatory disease that affects many women of fertile age, with no definitive cure and, in

  14. Host responses to Candida albicans: Th17 cells and mucosal candidiasis

    Science.gov (United States)

    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. PMID:20381638

  15. Force microscopic and thermodynamic analysis of the adhesion between Pseudomonas aeruginosa and Candida albicans

    NARCIS (Netherlands)

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

    2012-01-01

    Pseudomonas aeruginosa expresses a plethora of virulence factors and many species have developed warning systems to detect and evade P. aeruginosa. Candida albicans detects P. aeruginosa by sensing the secreted bacterial quorum sensing molecule 3OC(12)HSL and responds by reverting to the yeast

  16. Incidence of Candida Albicans in Pregnent Women: A Case Study of ...

    African Journals Online (AJOL)

    This study examines the incidence of Candida albicans among pregnant women of varied age range/occupation, within any of the three trimesters, and attending antenatal clinic in Ekpoma and its environs. A total of 100 high vagina swab- samples were collected from women and then transported to the Medical Laboratory ...

  17. Force microscopic and thermodynamic analysis of the adhesion between Pseudomonas aeruginosa and Candida albicans

    NARCIS (Netherlands)

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

    2012-01-01

    Pseudomonas aeruginosa expresses a plethora of virulence factors and many species have developed warning systems to detect and evade P. aeruginosa. Candida albicans detects P. aeruginosa by sensing the secreted bacterial quorum sensing molecule 3OC12HSL and responds by reverting to the yeast

  18. Comparative effect of propolis of honey bee and some herbal extracts on Candida albicans.

    Science.gov (United States)

    Gavanji, Shahin; Larki, Behrouz

    2017-03-01

    To determine the effect of propolis on Candida albicans and to compare it with the effects of some other herbal extracts and antibiotics on this pathogenic fungi. The extracts of propolis, Thymus vulgaris, Caryophillium aromaticus, Echinophora platyloba, Allium cepa and Cinnamomum zeylanicum were prepared and the antifungi effects of the extracts were examined on Candida albicans ATCC10231 using disc-diffusion assay and micro-broth dilution. The minimum fungicidal concentration (MFC) and minimum inhibitory concentrations (MIC) as well as inhibition zone were evaluated and the anti fungi effects of herbal extracts were compared with amphotricin B and nystatin at the times of 24, 48 and 72 h. Data analysis was performed using t test. Obtained results showed that propolis extract with MIC90 and MFC equal to 39 and 65 μg/mL, respectively, possess the highest antifungal activity when compared with other studied extracts. The extracts of Allium cepa and Thymus vulgaris, with MFC of 169 and 137 μg/mL, respectively, showed the lowest effects on the fungi. Also nystatin and amphotricin B yielded better effects on the tested fungi compared with the effects of all studied extracts on Candida albicans. Propolis extract is effective in controlling Candida albicans. However, the issue requires further investigation on samples in animals and performing toxicological examinations.

  19. Repurposing FDA approved drugs against the human fungal pathogen, Candida albicans.

    Science.gov (United States)

    Kim, Kevin; Zilbermintz, Leeor; Martchenko, Mikhail

    2015-06-09

    The high cost and prolonged timeline of new drug discovery and development are major roadblocks to creating therapies for infectious diseases. Candida albicans is an opportunistic fungal pathogen that is the most common cause of fatal fungal infections in humans and costs $2-4 billion dollars to treat in the US alone. To accelerate drug discovery, we screened a library of 1581 existing FDA approved drugs, as well as drugs approved abroad, for inhibitors of C. albicans. The screen was done on YPD yeast growth media as well as on the serum plate assay developed in this study. We discovered that fifteen drugs, all which were originally approved for treating various infectious and non-infectious diseases, were able to kill Candida albicans. Additionally, one of those drugs, Octodrine, displays wide-spectrum anti-microbial activity. Compared to other selected anti-Candida drugs, Octodrine was shown to be one of the most effective drugs in killing serum-grown Candida albicans without significantly affecting the survival of host macrophages and skin cells. This approach is useful for the discovery of economically viable new therapies against infectious diseases.

  20. Identification of salivary components that induce transition of hyphae to yeast in Candida albicans

    NARCIS (Netherlands)

    Leito, J.T.D.; Ligtenberg, A.J.M.; Nazmi, K.; Veerman, E.C.I.

    2009-01-01

    Candida albicans, the major human fungal pathogen, undergoes a reversible morphological transition from single yeast cells to pseudohyphae and hyphae filaments. The hyphae form is considered the most invasive form of the fungus. The purpose of this study is to investigate the effect of saliva on

  1. 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

  2. AKTIVITAS ANTIFUNGI EKSTRAK DAUN BELUNTAS, JAWER KOTOK, DAN SIRIH SERTA KOMBINASINYA TERHADAP Candida albicans

    Directory of Open Access Journals (Sweden)

    Umi Yuniarni

    2016-05-01

    Full Text Available Piper betle, Coleus scutellarioides and Pluchea indica have been used empirically to overcome vaginal discharge and scientifically proven to inhibit the growth of Candida albicans. The goal of this research was to search for a combined extract with effective antimicrobial activity against Candida albicans. Single extract,combination of two and three extracts evaluated antimicrobial activity against Candida albicans using agar diffusion method. Inhibitory effect of Piper betle showed the greatest activity against Candida albicans compared to other single extract. Combination of Piper betle and Pluchea indica (26.57±0.56 mm gave greater inhibition than two other combination extracts (Piper betle and Coleus scutellarioides (25.17±0.96 mm; Coleus scutellarioides and Pluchea indica (22.73±0.95 mm.The combination of Piper betle, Pluchea indica and Coleus scutellarioides gave inhibition of 27.53±1.10 mm. extracts did not give a better diameter compared to the betle extract.

  3. Adaptations of the secretome of Candida albicans in response to host-related environmental conditions

    NARCIS (Netherlands)

    Klis, F.M.; Brul, S.

    2015-01-01

    The wall proteome and the secretome of the fungal pathogen Candida albicans help it to thrive in multiple niches of the human body. Mass spectrometry has allowed researchers to study the dynamics of both subproteomes. Here we discuss some major responses of the secretome to host-related

  4. 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...

  5. Stability of candida albicans over long and short term storage in a ...

    African Journals Online (AJOL)

    METHODS: One hundred Candida albicans strains isolated from patients with vulvovaginal candidiasis and oral candidiasis were preserved in triplicates using sterile distilled water,Chromagar plate,mineral oil overlay and brain heart infusion broth plus 10% glycerol at -20OC.Recovery rates were determined at six months ...

  6. Streptococcus mutans competence-stimulating peptide inhibits Candida albicans hypha formation

    NARCIS (Netherlands)

    Jarosz, L.M.; Deng, D.M.; van der Mei, H.C.; Crielaard, W.; Krom, B.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

  7. 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

  8. Iron restriction-induced adaptations in the wall proteome of Candida albicans

    NARCIS (Netherlands)

    Sorgo, A.G.; Brul, S.; de Koster, C.G.; de Koning, L.J.; Klis, F.M.

    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.

  9. Infection related stress adaptations in the secretome and wall proteome of Candida albicans

    NARCIS (Netherlands)

    Sorgo, A.G.

    2013-01-01

    Alice Sorgo's main research question concerns the adaptability of the wall proteome and secretome of the opportunistic pathogenic fungus Candida albicans. The question is how do these subproteomes adapt to environmental stess (high temperatures, iron restriction, antifungal drugs) and how do these

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

    Science.gov (United States)

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

    2017-06-01

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

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

    Science.gov (United States)

    Liu, Yuan; Kim, Dongyeop; Li, Yong; Krysan, Damian J.

    2017-01-01

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

  12. Rapid detection of Candida albicans in oral exfoliative cytology samples by loop-mediated isothermal amplification.

    Science.gov (United States)

    Noguchi, Hiroyasu; Iwase, Takashi; Omagari, Daisuke; Asano, Masatake; Nakamura, Ryota; Ueki, Kosuke; Shinozuka, Keiji; Kaneko, Tadayoshi; Tonogi, Morio; Ohki, Hiderou

    2017-01-01

    Loop-mediated isothermal amplification (LAMP) rapidly amplifies DNA under isothermal conditions. The aim of this study was to detect Candida albicans and compare the positivity rate in the LAMP reaction with that of conventional methods for oral exfoliative cytology (EC) samples. Sixty-eight EC samples from 53 patients were subjected to LAMP analysis. These patients had been clinically diagnosed with leukoplakia, squamous cell carcinoma, oral lichen planus (OLP), stomatitis, oral candidiasis, and other malignancies. LAMP reactions were defined as positive when the sample turbidity exceeded 0.1 (arbitrary unit). Periodic acid-Schiff (PAS) staining and microbial culture were also performed to detect Candida species in EC samples. The LAMP reaction detected C. albicans in 42.6% of EC samples. Candida species were detected in 32.4% of the same samples by culturing and in 29.4% of samples by PAS staining. C. albicans DNA was detected most frequently in samples from OLP patients. We conclude that, in comparison to conventional methods for detection of C. albicans, the LAMP method is highly sensitive and time-saving, and does not require expensive equipment or diagnostic technology. It may therefore be useful for on-site screening of C. albicans at dental clinics.

  13. Effect of surface treatments of porcelain on adhesion of Candida albicans.

    Science.gov (United States)

    Lawaf, Shirin; Azizi, Arash; Farzad, Azin; Adimi, Parvaneh

    2016-01-01

    Surface treatment of porcelain is required to minimize the adhesion of microorganisms to surfaces of the restoration. This study sought to assess the effects of 3 different porcelain surface treatments on adhesion of Candida albicans. This in vitro experimental study was conducted on 60 porcelain disks (10 × 3 mm) randomly divided into 4 groups of 15. The nonglazed group received no surface treatment; specimens in the other 3 groups were glazed in the furnace, overglazed with liquid glaze, or polished using a polishing kit. The specimens were washed, sterilized, and separately incubated with 350 µL of Candida albicans suspension for 24 hours. Specimens were then rinsed for 20 seconds and shaken in 1 mL of saline solution for 1 minute, and 20 µL of this suspension was cultured in a plate and incubated at 37°C for 48 hours. Candida albicans colonies were counted to assess the number of microorganisms adhering to each disk. Data were analyzed with the Kruskal-Wallis test. Statistically significant differences were found among the 4 groups in terms of C albicans adherence (P = 0.001). The nonglazed porcelain had the highest and the overglazed porcelain had the lowest mean adherence value. No statistically significant difference was noted between glazed and polished specimens. Based on the obtained results, overglazing resulted in the least adhesion of C albicans, and polishing provided a surface as smooth as a glazed surface.

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

    Science.gov (United States)

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

    2016-12-01

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

  15. Influence of cancer treatment on the Candida albicans isolated from the oral cavities of cancer patients.

    Science.gov (United States)

    Ramla, Shilpa; Sharma, Vinay; Patel, Mrudula

    2016-06-01

    Cancer treatment causes mucositis and the manifestation of oral candidiasis. This study investigated the virulence properties and antifungal susceptibilities of Candida albicans isolated from cancer patients undergoing therapy. C. albicans were isolated from 49 patients on cancer treatment and 21 healthy individuals and their virulence attributes measured. A correlation was determined between the length of treatment and the fungal counts and their virulence factors. Although Candida carriage was similar in all the study groups, high quantities of C. albicans and variety of Candida were found in cancer patients. Germ tubes were produced by all the strains. Significantly high number of yeast isolated from radiotherapy and chemotherapy produced large quantities of phospholipase compared to healthy individuals (p albicans. Proteinase production was seen in a significant number of isolates from the radiotherapy group (p albicans in cancer patients on therapy which also increased with the length of chemotherapy suggesting enhanced risk of oral and systemic infection. Therefore, during treatment, prophylactic topical antifungal therapy may be considered.

  16. TNF- α expression on rats after Candida albicans inoculation and neem (Azadirachta indica extract feeding

    Directory of Open Access Journals (Sweden)

    I Dewa Ayu Ratna Dewanti

    2011-03-01

    Full Text Available Background: Neem is a known traditional medicine from trees which function as immunomodulator. Candidiasis found in mouth is 80% caused by Candida albicans (C. albicans. Immunity is important to limit C. albicans since medicine price is relatively traditional medicine may become a good choice. In the other side the medicine price may not be reached by the citizen, cause citizen choose the traditional medicine. Purpose: The research is aimed to explain of TNF-α expression on rats after inoculated by C. albicans and fed with neem extract (Azadirachta Indica. Methods: There were 5 groups, the first group which was called as control group (KO hadn’t been fed aqueous extract from neem leaves and was not inoculated by C. albicans, the other group (treatment was classified into 4 groups. The first group was inoculated by C. albicans only (KP1, second group was fed with 50 mg/day/kg body weight aqueous extracts from Neem leaves, then inoculated with C. albicans starting from day 8 until day 21 (KP2, third group was fed with 100 mg/day/kg body weight aqueous extract from Neem leaves, then inoculated with C. albicans start from day 8 until day 21 (KP3, fourth group was fed with 200 mg/day/kg body weight aqueous extract from Neem leaves, then inoculated by C. albicans start from day 8 until day 21 (KP4. The data was collected from by swabbing the rat’s tongue to calculate C. albicans colonies. The rats were acclimated and collected for immunohistochemistry measurement. Results: The study showed that there were different result on ANOVA, HSD test, and linier regression. ANOVA showed significant difference (p < 0.01 between groups. The HSD test showed significant difference (p < 0.05 between each groups. TNF-α was the stimuli sensor from environment, and used as parameter to see the effect from the change of innate immunity component to C. albicans. Conclusion: Aqueous extract from neem leaves increased the macrophage TNF-α expression on in rat in

  17. Phenotypic plasticity regulates Candida albicans interactions and virulence in the vertebrate host

    Directory of Open Access Journals (Sweden)

    Emily M Mallick

    2016-05-01

    Full Text Available Phenotypic diversity is critical to the lifestyles of many microbial species, enabling rapid responses to changes in environmental conditions. In the human fungal pathogen Candida albicans, cells exhibit heritable switching between two phenotypic states, white and opaque, which yield differences in mating, filamentous growth, and interactions with immune cells in vitro. Here, we addressed the in vivo properties of the two cell states in a zebrafish model of infection. Multiple attributes were compared including the stability of phenotypic states, filamentation, virulence, dissemination, and phagocytosis by immune cells, and phenotypes equated across three different host temperatures. We show that both white and opaque cells can establish a lethal systemic infection. The relative virulence of the two cell types is temperature dependent; virulence is similar at 25°C, but at higher temperatures (30 and 33°C white cells are significantly more virulent than opaque cells. Despite the difference in virulence, fungal burdens and dissemination are similar between cells in the two states. Additionally, both white and opaque cells exhibit robust filamentation during infection, and mutants unable to filament show decreased virulence, establishing that this program is critical for pathogenesis in both cell states. Interactions between C. albicans cells and immune cells were compared both in vitro and in vivo. Macrophages and neutrophils preferentially phagocytosed white cells over opaque cells in vitro, and neutrophils also showed preferential phagocytosis of white cells in vivo. Together, these studies distinguish the properties of white and opaque cells in a vertebrate host, and establish that the two cell types demonstrate both important similarities and key differences during infection.

  18. 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

  19. Effects of cefepime, cefixime and ceftibuten on murine gut colonization by Candida albicans.

    Science.gov (United States)

    Maraki, S; Barbounakis, E; Chatzinikolaou, I; Anatoliotakis, N; Plataki, M; Tselentis, Y; Samonis, G

    1998-01-01

    Crl:CD1(ICR) BR mice were fed chow containing Candida albicans or regular chow. Both groups were subsequently given either antibiotics or normal saline. Stool cultures were performed before, at the end of treatment and 1 week after treatment, to determine the effect on the stool yeast concentration. Candida-colonized mice treated with cefepime, cefixime or ceftibuten had higher (however not significantly) counts of the yeast in their stools than control Candida-fed mice treated with saline. A group of Candida-fed mice were treated with ceftriaxone, which is known to increase the yeast stool concentration significantly and served as positive control. Mice fed regular chow and treated with the study drugs or saline did not have any yeasts in their stools. Dissemination of Candida did not occur.

  20. 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.

  1. Hexosomes with Undecylenic Acid Efficient against Candida albicans

    Directory of Open Access Journals (Sweden)

    Marijana Mionić Ebersold

    2018-02-01

    Full Text Available Due to the growing issues with fungal infections, especially with Candida, there is still a need to develop novel anti-Candida materials. One of the known antifungal agents is undecylenic acid (UA, which still cannot be efficiently used due to its oily nature, and thus limited solubility. By taking advantage of the properties of UA, we developed an emulsion with hexagonal phase, i.e., hexosomes, whose structure and morphology was studied by small-angle X-ray scattering and cryo-electron microscopy, respectively. The presence of UA in the hexosome was confirmed by spectroscopy. Moreover, we studied the anti-Candida effect of hexosomes and their cytotoxicity toward human cells. The minimal inhibitory concentration for the 50% and 90% Candida-growth reduction was found at 0.01 and 0.16 wt % hexosomes, respectively (i.e., 2 and 32 pghex/C.a.cell, respectively. The percentage of metabolically active Candida was reduced by 72–96% at hexosome concentrations of 1.0–8.2 pghex/C.a.cell as compared to untreated Candida. Furthermore, at the same concentration range the embedded filamentation test after 24 and 48 h showed the inhibition of both the filamentation and growth of Candida, while the preliminary toxicity test showed that hexosomes were nontoxic for human cells. All these render the here-developed hexosomes with UA efficient and promising anti-Candida agents.

  2. 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.

  3. Paeonia lactiflora Inhibits Cell Wall Synthesis and Triggers Membrane Depolarization in Candida albicans.

    Science.gov (United States)

    Lee, Heung-Shick; Kim, Younhee

    2017-02-28

    Fungal cell walls and cell membranes are the main targets of antifungals. In this study, we report on the antifungal activity of an ethanol extract from Paeonia lactiflora against Candida albicans, showing that the antifungal activity is associated with the synergistic actions of preventing cell wall synthesis, enabling membrane depolarization, and compromising permeability. First, it was shown that the ethanol extract from P. lactiflora was involved in damaging the integrity of cell walls in C. albicans. In isotonic media, cell bursts of C. albicans by the P. lactiflora ethanol extract could be restored, and the minimum inhibitory concentration (MIC) of the P. lactiflora ethanol extract against C. albicans cells increased 4-fold. In addition, synthesis of (1,3)-β-D-glucan polymer was inhibited by 87% and 83% following treatment of C. albicans microsomes with the P. lactiflora ethanol extract at their 1× MIC and 2× MIC, respectively. Second, the ethanol extract from P. lactiflora influenced the function of C. albicans cell membranes. C. albicans cells treated with the P. lactiflora ethanol extract formed red aggregates by staining with a membrane-impermeable dye, propidium iodide. Membrane depolarization manifested as increased fluorescence intensity by staining P. lactiflora-treated C. albicans cells with a membrane-potential marker, DiBAC4(3) ((bis-1,3-dibutylbarbituric acid) trimethine oxonol). Membrane permeability was assessed by crystal violet assay, and C. albicans cells treated with the P. lactiflora ethanol extract exhibited significant uptake of crystal violet in a concentration-dependent manner. The findings suggest that P. lactiflora ethanol extract is a viable and effective candidate for the development of new antifungal agents to treat Candida-associated diseases.

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    S R Fule

    2015-01-01

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

  6. Dynamic Transcript Profiling of Candida albicans Infection in Zebrafish: A Pathogen-Host Interaction Study

    Science.gov (United States)

    Liu, Fu-Chen; Hsu, Po-Chen; Chen, Hsueh-Fen; Peng, Shih-Chi; Chuang, Yung-Jen; Lan, Chung-Yu; Hsieh, Wen-Ping; Wong, David Shan Hill

    2013-01-01

    Candida albicans is responsible for a number of life-threatening infections and causes considerable morbidity and mortality in immunocompromised patients. Previous studies of C. albicans pathogenesis have suggested several steps must occur before virulent infection, including early adhesion, invasion, and late tissue damage. However, the mechanism that triggers C. albicans transformation from yeast to hyphae form during infection has yet to be fully elucidated. This study used a systems biology approach to investigate C. albicans infection in zebrafish. The surviving fish were sampled at different post-infection time points to obtain time-lapsed, genome-wide transcriptomic data from both organisms, which were accompanied with in sync histological analyses. Principal component analysis (PCA) was used to analyze the dynamic gene expression profiles of significant variations in both C. albicans and zebrafish. The results categorized C. albicans infection into three progressing phases: adhesion, invasion, and damage. Such findings were highly supported by the corresponding histological analysis. Furthermore, the dynamic interspecies transcript profiling revealed that C. albicans activated its filamentous formation during invasion and the iron scavenging functions during the damage phases, whereas zebrafish ceased its iron homeostasis function following massive hemorrhage during the later stages of infection. Most of the immune related genes were expressed as the infection progressed from invasion to the damage phase. Such global, inter-species evidence of virulence-immune and iron competition dynamics during C. albicans infection could be crucial in understanding control fungal pathogenesis. PMID:24019870

  7. Lack of trehalose accelerates H2O2-induced Candida albicans apoptosis through regulating Ca2+ signaling pathway and caspase activity.

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    Hui Lu

    Full Text Available Trehalose is a non-reducing disaccharide and can be accumulated in response to heat or oxidative stresses in Candida albicans. Here we showed that a C. albicans tps1Δ mutant, which is deficient in trehalose synthesis, exhibited increased apoptosis rate upon H(2O(2 treatment together with an increase of intracellular Ca(2+ level and caspase activity. When the intracellular Ca(2+ level was stimulated by adding CaCl(2 or A23187, both the apoptosis rate and caspase activity were increased. In contrast, the presence of two calcium chelators, EGTA and BAPTA, could attenuate these effects. Moreover, we investigated the role of Ca(2+ pathway in C. albicans apoptosis and found that both calcineurin and the calcineurin-dependent transcription factor, Crz1p, mutants showed decreased apoptosis and caspase activity upon H(2O(2 treatment compared to the wild-type cells. Expression of CaMCA1, the only gene found encoding a C. albicans metacaspase, in calcineurin-deleted or Crz1p-deleted cells restored the cell sensitivity to H(2O(2. Our results suggest that Ca(2+ and its downstream calcineurin/Crz1p/CaMCA1 pathway are involved in H(2O(2-induced C. albicans apoptosis. Inhibition of this pathway might be the mechanism for the protective role of trehalose in C. albicans.

  8. Genotyping and Persistence of Candida albicans from Pregnant Women with Vulvovaginal Candidiasis.

    Science.gov (United States)

    Tapia, Cecilia V; Hermosilla, Germán; Fortes, Paula; Alburquenque, Claudio; Bucarey, Sergio; Salinas, Hugo; Rodas, Paula I; Díaz, María Cristina; Magne, Fabien

    2017-04-01

    To study Candida albicans genotypes using RAPD and their susceptibility to fluconazole in healthy pregnant women and in vulvovaginal candidiasis (VVC) patients after topical treatment with clotrimazole. Vaginal swabs were collected at t = 0 and t = 1 (1 month later) in pregnant women (control group, n = 33), and before (t = 0), at 1 month (t = 1) and at 2 months (t = 2) after clotrimazole treatment in pregnant women with VVC. Candida albicans was isolated in 30% of healthy pregnant women and 80% of patients with VVC. A high genetic heterogeneity was observed in C. albicans genotypes between individuals. In patients with VVC, topical antifungal treatment with clotrimazole was clinically effective, but only in a 62% C. albicans was eradicated. In patients in which C. albicans was not eradicated, this microorganism persisted for 1 or 2 months after the antifungal treatment. The persistent colonies were not associated with a specific genotype, but they were associated with higher MICs in comparison with colonies isolated from the control group. Therapy with topical clotrimazole, despite a good clinical outcome, could not eradicate completely C. albicans allowing the persistence of genotypes, with higher MICs to fluconazole. More studies with higher number of patients are needed to validate this preliminary finding.

  9. 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.

  10. 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

  11. Phenotypic and genotypic detection of Candida albicans and Candida dubliniensis strains isolated from oral mucosa of AIDS pediatric patients.

    Science.gov (United States)

    Livério, Harisson Oliveira; Ruiz, Luciana da Silva; Freitas, Roseli Santos de; Nishikaku, Angela; Souza, Ana Clara de; Paula, Claudete Rodrigues; Domaneschi, Carina

    2017-04-13

    The aim of this study was to assess a collection of yeasts to verify the presence of Candida dubliniensis among strains isolated from the oral mucosa of AIDS pediatric patients which were initially characterized as Candida albicans by the traditional phenotypic method, as well as to evaluate the main phenotypic methods used in the discrimination between the two species and confirm the identification through genotypic techniques, i.e., DNA sequencing. Twenty-nine samples of C. albicans isolated from this population and kept in a fungi collection were evaluated and re-characterized. In order to differentiate the two species, phenotypic tests (Thermotolerance tests, Chromogenic medium, Staib agar, Tobacco agar, Hypertonic medium) were performed and genotypic techniques using DNA sequencing were employed for confirmation of isolated species. Susceptibility and specificity were calculated for each test. No phenotypic test alone was sufficient to provide definitive identification of C. dubliniensis or C. albicans, as opposed to results of molecular tests. After amplification and sequencing of specific regions of the 29 studied strains, 93.1% of the isolates were identified as C. albicans and 6.9% as C. dubliniensis. The Staib agar assay showed a higher susceptibility (96.3%) in comparison with other phenotypic techniques. Therefore, genotypic methods are indispensable for the conclusive identification and differentiation between these species.

  12. Comparison of duplex PCR and phenotypic analysis in differentiating Candida dubliniensis from Candida albicans from oral samples.

    Science.gov (United States)

    Sampath, Asanga; Weerasekera, Manjula; Dilhari, Ayomi; Gunasekara, Chinthika; Bulugahapitiya, Uditha; Fernando, Neluka; Samaranayake, Lakshman

    2017-12-01

    Candida dubliniensis shares a wide range of phenotypic characteristics with Candida albicans including a common trait called germ tube positivity. Hence, laboratory differentiation of these two species is cumbersome. Duplex PCR analyses for C. albicans and C. dubliniensis was performed directly on DNA extracted from a total of 122 germ tube positive isolates derived from 100 concentrated oral rinse samples from a random cohort of diabetics attending a clinic in Sri Lanka. These results were confirmed by DNA sequencing of internal transcribed spacer (ITS) region of rDNA of the yeasts. Performance efficacy of duplex PCR was then compared with phenotypic identification using a standard battery of phenotypic tests. Of the 122 germ tube positive isolates three were identified by duplex PCR as C. dubliniensis and the remainder as C. albicans. On the contrary, when the standard phenotypic tests, sugar assimilation and chlamydospore formation, were used to differentiate the two species 13 germ tube positive isolates were erroneously identified as C. dubliniensis. Duplex PCR was found to be rapid, sensitive and more specific than phenotypic identification methods in discriminating C. dubliniensis from C. albicans. This is also the first report on the oral carriage of C. dubliniensis in a Sri Lankan population.

  13. Rad51-Rad52 mediated maintenance of centromeric chromatin in Candida albicans.

    Directory of Open Access Journals (Sweden)

    Sreyoshi Mitra

    2014-04-01

    Full Text Available Specification of the centromere location in most eukaryotes is not solely dependent on the DNA sequence. However, the non-genetic determinants of centromere identity are not clearly defined. While multiple mechanisms, individually or in concert, may specify centromeres epigenetically, most studies in this area are focused on a universal factor, a centromere-specific histone H3 variant CENP-A, often considered as the epigenetic determinant of centromere identity. In spite of variable timing of its loading at centromeres across species, a replication coupled early S phase deposition of CENP-A is found in most yeast centromeres. Centromeres are the earliest replicating chromosomal regions in a pathogenic budding yeast Candida albicans. Using a 2-dimensional agarose gel electrophoresis assay, we identify replication origins (ORI7-LI and ORI7-RI proximal to an early replicating centromere (CEN7 in C. albicans. We show that the replication forks stall at CEN7 in a kinetochore dependent manner and fork stalling is reduced in the absence of the homologous recombination (HR proteins Rad51 and Rad52. Deletion of ORI7-RI causes a significant reduction in the stalled fork signal and an increased loss rate of the altered chromosome 7. The HR proteins, Rad51 and Rad52, have been shown to play a role in fork restart. Confocal microscopy shows declustered kinetochores in rad51 and rad52 mutants, which are evidence of kinetochore disintegrity. CENP-ACaCse4 levels at centromeres, as determined by chromatin immunoprecipitation (ChIP experiments, are reduced in absence of Rad51/Rad52 resulting in disruption of the kinetochore structure. Moreover, western blot analysis reveals that delocalized CENP-A molecules in HR mutants degrade in a similar fashion as in other kinetochore mutants described before. Finally, co-immunoprecipitation assays indicate that Rad51 and Rad52 physically interact with CENP-ACaCse4 in vivo. Thus, the HR proteins Rad51 and Rad52

  14. Mnn10 Maintains Pathogenicity in Candida albicans by Extending α-1,6-Mannose Backbone to Evade Host Dectin-1 Mediated Antifungal Immunity.

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    Shi Qun Zhang

    2016-05-01

    Full Text Available The cell wall is a dynamic structure that is important for the pathogenicity of Candida albicans. Mannan, which is located in the outermost layer of the cell wall, has been shown to contribute to the pathogenesis of C. albicans, however, the molecular mechanism by which this occurs remains unclear. Here we identified a novel α-1,6-mannosyltransferase encoded by MNN10 in C. albicans. We found that Mnn10 is required for cell wall α-1,6-mannose backbone biosynthesis and polysaccharides organization. Deletion of MNN10 resulted in significant attenuation of the pathogenesis of C. albicans in a murine systemic candidiasis model. Inhibition of α-1,6-mannose backbone extension did not, however, impact the invasive ability of C. albicans in vitro. Notably, mnn10 mutant restored the invasive capacity in athymic nude mice, which further supports the notion of an enhanced host antifungal defense related to this backbone change. Mnn10 mutant induced enhanced Th1 and Th17 cell mediated antifungal immunity, and resulted in enhanced recruitment of neutrophils and monocytes for pathogen clearance in vivo. We also demonstrated that MNN10 could unmask the surface β-(1,3-glucan, a crucial pathogen-associated molecular pattern (PAMP of C. albicans recognized by host Dectin-1. Our results demonstrate that mnn10 mutant could stimulate an enhanced Dectin-1 dependent immune response of macrophages in vitro, including the activation of nuclear factor-κB, mitogen-activated protein kinase pathways, and secretion of specific cytokines such as TNF-α, IL-6, IL-1β and IL-12p40. In summary, our study indicated that α-1,6-mannose backbone is critical for the pathogenesis of C. albicans via shielding β-glucan from recognition by host Dectin-1 mediated immune recognition. Moreover, our work suggests that inhibition of α-1,6-mannose extension by Mnn10 may represent a novel modality to reduce the pathogenicity of C. albicans.

  15. 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

    2013-01-29

    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

  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. 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.

  18. Lactobacillus is able to alter the virulence and the sensitivity profile of Candida albicans.

    Science.gov (United States)

    Oliveira, V M C; Santos, S S F; Silva, C R G; Jorge, A O C; Leão, M V P

    2016-12-01

    The study investigated whether the interaction with Lactobacillus rhamnosus (ATCC7469) interfere with the expression of virulence factors by Candida albicans (ATCC18804). These micro-organisms were grown in biofilms for 24, 48 and 72 h, Candida was isolated and the expression of the major virulence factors were investigated. The production of phospholipase, protease and haemolysin were observed in appropriate media; observation of germ tubes formation in serum; biofilm formation, after growth in microtitre plates and reading in spectrophotometer. Candida was also tested for antifungal sensitivity to amphotericin B, fluconazole and ketoconazole. The results were compared with the cells of Candida grown in the absence of lactobacilli (control group). Candida cells, which interacted with Lact. rhamnosus (test group), showed significantly lower proteinase and haemolysin activity, when compared with control group. The germ tube formation and biofilm formation capacity also decreased in tested groups, which demonstrated alterations in susceptibility to antifungal drugs. The results suggest that Lact. rhamnosus is able to influence the expression of virulence factors by C. albicans and can alter its antifungal sensitivity profile. These results suggest reduction in the pathogenicity of Candida and improvement in candidiasis therapy and control. © 2016 The Society for Applied Microbiology.

  19. Candida albicans Ethanol Stimulates Pseudomonas aeruginosa WspR-Controlled Biofilm Formation as Part of a Cyclic Relationship Involving Phenazines

    Science.gov (United States)

    Okegbe, Chinweike; Harty, Colleen E.; Golub, Yuriy; Thao, Sandy; Ha, Dae Gon; Willger, Sven D.; O'Toole, George A.; Harwood, Caroline S.; Dietrich, Lars E. P.; Hogan, Deborah A.

    2014-01-01

    In chronic infections, pathogens are often in the presence of other microbial species. For example, Pseudomonas aeruginosa is a common and detrimental lung pathogen in individuals with cystic fibrosis (CF) and co-infections with Candida albicans are common. Here, we show that P. aeruginosa biofilm formation and phenazine production were strongly influenced by ethanol produced by the fungus C. albicans. Ethanol stimulated phenotypes that are indicative of increased levels of cyclic-di-GMP (c-di-GMP), and levels of c-di-GMP were 2-fold higher in the presence of ethanol. Through a genetic screen, we found that the diguanylate cyclase WspR was required for ethanol stimulation of c-di-GMP. Multiple lines of evidence indicate that ethanol stimulates WspR signaling through its cognate sensor WspA, and promotes WspR-dependent activation of Pel exopolysaccharide production, which contributes to biofilm maturation. We also found that ethanol stimulation of WspR promoted P. aeruginosa colonization of CF airway epithelial cells. P. aeruginosa production of phenazines occurs both in the CF lung and in culture, and phenazines enhance ethanol production by C. albicans. Using a C. albicans adh1/adh1 mutant with decreased ethanol production, we found that fungal ethanol strongly altered the spectrum of P. aeruginosa phenazines in favor of those that are most effective against fungi. Thus, a feedback cycle comprised of ethanol and phenazines drives this polymicrobial interaction, and these relationships may provide insight into why co-infection with both P. aeruginosa and C. albicans has been associated with worse outcomes in cystic fibrosis. PMID:25340349

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

    Directory of Open Access Journals (Sweden)

    Annie I Chen

    2014-10-01

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

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

    Science.gov (United States)

    Chin, Voon Kin; Lee, Tze Yan; Rusliza, Basir; Chong, Pei Pei

    2016-10-18

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

  2. Virtual screening of inhibitory compounds SEP-2 Candida albicans

    OpenAIRE

    Rebollo, Juan; Doctorando, Grupo de genética y biología molecular. Sección de Microbiología, Facultad de Medicina, Universidad de Cartagena.; Reyes, Niradiz; Docente, Grupo de genética y biología molecular. Sección de Microbiología, Facultad de Medicina, Universidad de Cartagena.; Suárez, Paola; Docente, Grupo de Micología. Sección de Microbiología, Facultad de Medicina, Universidad de Cartagena.

    2015-01-01

    Objetive: reports of Antifungal resistance to Candida spp. are increasing nowadays. Candida spp. is an opportunistic yeast associated to many different mucocutaneous and systemic diseases. Because of this problematic is necessary to search others new selective and specific compounds against this fungi. Virtual docking is a good alternative to study new molecules. Materials and Methods: here we analyse 13418 compoundssimilar to recognized inhibitors of SAP-2, the enzyme selected as antifungal ...

  3. [Adhesion of clinical Candida albicans isolate to buccal epithelial cells].

    Science.gov (United States)

    Wellmer, A

    1999-01-01

    Mucosal adherence and germ tube formation are considered to be important virulence factors of C. albicans. Adherence is a precondition for colonisation and invasion. We investigated 11 clinical isolates (among them 5 cases recovered from oesophageal thrush) for quantification of the two characteristics and correlated the results with clinical data. Adherence was measured on buccal epithelial cells and the continuous flow culture was used for quantification of germ tube formation. Adherence of strains recovered from clinically, culturally and serologically confirmed oesophageal thrush adhered stronger to buccal epithelial cells than isolates from patients with heavy colonisation without signs of candidosis. Strains with stronger adherence showed a significantly faster and an increased germ tube formation in the continuous flow culture. Strains from oesophageal thrush therefore show a more marked expression of the investigated virulence factors. Therefore a good adherence is a necessity for infection of the oesophagus by C. albicans. The preferential isolation of C. albicans from oesophageal thrush (> 90%) supports this assumption.

  4. Evaluation of anti-enzyme properties of Origanum vulgare essential oil against oral Candida albicans.

    Science.gov (United States)

    Pradebon Brondani, L; Alves da Silva Neto, T; Antonio Freitag, R; Guerra Lund, R

    2018-02-02

    This study aimed to evaluate the anti-enzymatic activity of Origanum vulgare (oregano) essential oil against 15 strains of Candida albicans. Candida albicans samples were isolated from the oral mucosa of patients with denture stomatitis treated in a Dentistry school on a public university. Preparation of the inoculum was performed with a suspension of C. albicans reactivated 24h earlier in 5mL of sterile phosphate buffer saline (PBS) adjusted to a 0.5-turbidity on the MacFarland scale (1,5×108UFC/mL). The essential oil was obtained by hydrodistillation in a Clevenger-type machine and analyzed by gas chromatography. Enzymatic assay was performed to test phospholipase anti-enzymatic properties. Chromatography analysis revealed that the main compounds present in the essential oil were 4-terpineol (41.17%), thymol (21.95%), γ-terpinene (5.91%) and carvacrol (4.71%). For the anti-enzymatic test, the statistical analysis showed that there was found statistically significant interactions between the factors time and concentration (P≤0,001). Thus, essential oil of oregano at 1%, 5% and 10% presented significant reductions in the production of the phospholipase enzyme produced by Candida albicans strains. However, the longer the incubation time of the essential oil, there is a relatively moderate reduction in its anti-enzymatic activity. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  5. Identification and characterization of MFA1, the gene encoding Candida albicans a-factor pheromone.

    Science.gov (United States)

    Dignard, Daniel; El-Naggar, Ahmed L; Logue, Mary E; Butler, Geraldine; Whiteway, Malcolm

    2007-03-01

    In the opaque state, MTLa and MTLalpha strains of Candida albicans are able to mate, and this mating is directed by a pheromone-mediated signaling process. We have used comparisons of genome sequences to identify a C. albicans gene encoding a candidate a-specific mating factor. This gene is conserved in Candida dubliniensis and is similar to a three-gene family in the related fungus Candida parapsilosis but has extremely limited similarity to the Saccharomyces cerevisiae MFA1 (ScMFA1) and ScMFA2 genes. All these genes encode C-terminal CAAX box motifs characteristic of prenylated proteins. The C. albicans gene, designated CaMFA1, is found on chromosome 2 between ORF19.2165 and ORF19.2219. MFA1 encodes an open reading frame of 42 amino acids that is predicted to be processed to a 14-amino-acid prenylated mature pheromone. Microarray analysis shows that MFA1 is poorly expressed in opaque MTLa cells but is induced when the cells are treated with alpha-factor. Disruption of this C. albicans gene blocks the mating of MTLa cells but not MTLalpha cells, while the reintegration of the gene suppresses this cell-type-specific mating defect.

  6. 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

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

    Science.gov (United States)

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

    2016-01-01

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

  8. 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.

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

    Directory of Open Access Journals (Sweden)

    Júnia Oliveira Barbosa

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

  10. 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. Copyright © 2015 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. Comparison between Iranian and foreign mouthwashes effect against Candida albicans as a common fungal mouth flora

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    Somayeh Talebi

    2015-02-01

    Full Text Available   Introduction : Candida albicans has been isolated in up to 65% of healthy individuals without signs of clinical disease. Mouthwashes can be used for many preventative and therapeutic purposes. This study evaluates the effectiveness of Iranian and foreign mouthwashes against C.albicans as a common fungal flora in the mouth.   Materials and method s: In this research, standard strain of C.albicans, ATCC 10231 is used. The suspension is provided by a fresh culture of C.albicans (24 hours and the OD is read in 530 nm. The C. albicans suspension was cultured on Sabouraud dextrose agar plate. In the next step, two wells created on SDA, filling with mouthwashes (100 µl. After incubation at 37ºC for 24 hours, the inhibition zone was measured. Minimum inhibitory concentration (MIC and Minimum fungicidal concentration (MFC of mouthwashes were determined. The data are analyzed by SPSS software, independent T-tests and one sided variance analysis (ANOVA-one way.   Results : Findings of our study showed in which agar diffusion, MIC and MFC tests, there are no significant differences between the antifungal effect of the Iranian and foreign mouthwashes on C.albicans (P value>0.05 .   Discussion and conclusion : This study shows that both Iranian and foreign mouthwashes have a good effect against C.albicans, as a common fungal flora in the mouth.

  12. Ambroxol Hydrochloride Combined with Fluconazole Reverses the Resistance of Candida albicans to Fluconazole.

    Science.gov (United States)

    Li, Xiuyun; Zhao, Yuanhao; Huang, Xin; Yu, Cuixiang; Yang, Yilei; Sun, Shujuan

    2017-01-01

    In this study, we found that ambroxol hydrochloride (128 μg/mL) exhibits synergistic antifungal effects in combination with fluconazole (2 μg/mL) against resistant planktonic Candida albicans (C. albicans) cells. This combination also exhibited synergistic effects against resistant C. albicans biofilms in different stages (4, 8, and 12 h) according to the microdilution method. In vitro data were further confirmed by the success of this combination in treating Galleria mellonella infected by resistant C. albicans. With respect to the synergistic mechanism, our result revealed that ambroxol hydrochloride has an effect on the drug transporters of resistant C. albicans, increasing the uptake and decreasing the efflux of rhodamine 6G, a fluorescent alternate of fluconazole. This is the first study to investigate the in vitro and in vivo antifungal effects, as well as the possible synergistic mechanism of ambroxol hydrochloride in combination with fluconazole against resistant C. albicans. The results show the potential role for this drug combination as a therapeutic alternative to treat resistant C. albicans and provide insights into the development of antifungal targets and new antifungal agents.

  13. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-09-15

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

  15. Genome-wide fitness test and mechanism-of-action studies of inhibitory compounds in Candida albicans.

    Directory of Open Access Journals (Sweden)

    Deming Xu

    2007-06-01

    Full Text Available Candida albicans is a prevalent fungal pathogen amongst the immunocompromised population, causing both superficial and life-threatening infections. Since C. albicans is diploid, classical transmission genetics can not be performed to study specific aspects of its biology and pathogenesis. Here, we exploit the diploid status of C. albicans by constructing a library of 2,868 heterozygous deletion mutants and screening this collection using 35 known or novel compounds to survey chemically induced haploinsufficiency in the pathogen. In this reverse genetic assay termed the fitness test, genes related to the mechanism of action of the probe compounds are clearly identified, supporting their functional roles and genetic interactions. In this report, chemical-genetic relationships are provided for multiple FDA-approved antifungal drugs (fluconazole, voriconazole, caspofungin, 5-fluorocytosine, and amphotericin B as well as additional compounds targeting ergosterol, fatty acid and sphingolipid biosynthesis, microtubules, actin, secretion, rRNA processing, translation, glycosylation, and protein folding mechanisms. We also demonstrate how chemically induced haploinsufficiency profiles can be used to identify the mechanism of action of novel antifungal agents, thereby illustrating the potential utility of this approach to antifungal drug discovery.

  16. The role of Bgl2p in the transition to filamentous cells during biofilm formation by Candida albicans.

    Science.gov (United States)

    Chen, Xinyue; Zhang, Ruoyu; Takada, Ayako; Iwatani, Shun; Oka, Chiemi; Kitamoto, Toshitaka; Kajiwara, Susumu

    2017-02-01

    The fungal pathogen Candida albicans undergoes a transition from yeast cells to filamentous cells that is related to its pathogenicity. The complex multicellular processes involved in biofilm formation by this fungus also include this transition. In this work, we investigated the morphological role of the Bgl2 protein (Bgl2p) in the transition to filamentous cells during biofilm formation by C. albicans. Bgl2p has been identified as a β-1, 3-glucosyltransferase, and transcription of the CaBGL2 gene is upregulated during biofilm formation. We used scanning electron microscopy to observe the microstructure of a bgl2 null mutant during biofilm formation and found a delay in the transition to filamentous cells in the premature phase (24 hours) of biofilm formation. Deletion of the CaBGL2 gene led to a decrease in the expression of CPH2 and TEC1, which encode transcription factors required for the transition to the filamentous form. These findings indicate that Bgl2p plays a role in the transition to filamentous cells during biofilm formation by C. albicans. © 2016 Blackwell Verlag GmbH.

  17. Comparing antifungal effects of Zatariamultiflora and Punicagranatum extract with Nystatin on Candida Albicans

    Directory of Open Access Journals (Sweden)

    F. Nouri

    2016-12-01

    Full Text Available Background: Despite all the progress that has been made in the manufacture of synthetic drugs, herbal drugs are increasingly taken into account. This is due to the growing belief that they have fewer side effects compared to synthetic ones. Objective: To compare the antifungal effects of extracts of Zatariamultiflora and Punicagranatum with Nystatin on Candida Albicans. Methods: This inviro trial accomplished in the school of dentistry of Tehran University in 2012. From the mouths of 25 patients with denture stomatitis were sampled using sterile swabs. Candida Albicans strains were isolated from samples and standard Candida Albicans PTCC 5027 were cultured too. Then extract of Zatariamultiflora and Punicagranatum to be obtained and antifungal of extract studied with disk diffusion method. Antifungal power of each of the extracts on the inhibition zone diameter was created in the medium. Data were analyzed by ANOVA and Friedman statistical tests. Findings: Results showed extracts of Zataria and pomegranate flowers have antifungal significant effects (P<0.001. Diameter of inhabitation zone was 17.66±./75 mm in Nystatin group and in the Zataria and pomegranate flowers extracts groups was lower (P<0.001. None of the negative control disc did inhibition zone in the medium. Conclusion: With due attention of Zataria and pomegranate flowers extracts exhibited antifungal effects on Candida Albincans.

  18. Regulation of the Cdc42/Cdc24 GTPase module during Candida albicans hyphal growth.

    Science.gov (United States)

    Bassilana, Martine; Hopkins, Julie; Arkowitz, Robert A

    2005-03-01

    The Rho G protein Cdc42 and its exchange factor Cdc24 are required for hyphal growth of the human fungal pathogen Candida albicans. Previously, we reported that strains ectopically expressing Cdc24 or Cdc42 are unable to form hyphae in response to serum. Here we investigated the role of these two proteins in hyphal growth, using quantitative real-time PCR to measure induction of hypha-specific genes together with time lapse microscopy. Expression of the hypha-specific genes examined depends on the cyclic AMP-dependent protein kinase A pathway culminating in the Efg1 and Tec1 transcription factors. We show that strains with reduced levels of CDC24 or CDC42 transcripts induce hypha-specific genes yet cannot maintain their expression in response to serum. Furthermore, in serum these mutants form elongated buds compared to the wild type and mutant budding cells, as observed by time lapse microscopy. Using Cdc24 fused to green fluorescent protein, we also show that Cdc24 is recruited to and persists at the germ tube tip during hyphal growth. Altogether these data demonstrate that the Cdc24/Cdc42 GTPase module is required for maintenance of hyphal growth. In addition, overexpression studies indicate that specific levels of Cdc24 and Cdc42 are important for invasive hyphal growth. In response to serum, CDC24 transcript levels increase transiently in a Tec1-dependent fashion, as do the G-protein RHO3 and the Rho1 GTPase activating protein BEM2 transcript levels. These results suggest that a positive feedback loop between Cdc24 and Tec1 contributes to an increase in active Cdc42 at the tip of the germ tube which is important for hypha formation.

  19. The antimicrobial effects of selenium nanoparticle-enriched probiotics and their fermented broth against Candida albicans.

    Science.gov (United States)

    Kheradmand, Erfan; Rafii, Fatemeh; Yazdi, Mohammad Hossien; Sepahi, Abas Akhavan; Shahverdi, Ahmad Reza; Oveisi, Mohammad Reza

    2014-06-06

    Lactic acid bacteria are considered important probiotics for prevention of some infections. The aim of this work was to investigate the effect of selenium dioxide on the antifungal activity of Lactobacillus plantarum and L. johnsonii against Candida albicans. Lactobacillus plantarum and L. johnsonii cells, grown in the presence and absence of selenium dioxide, and their cell-free spent culture media were tested for antifungal activity against C. albicans ATCC 14053 by a hole-plate diffusion method and a time-kill assay. Both L. plantarum and L. johnsonii reduced selenium dioxide to cell-associated elemental selenium nanoparticles. The cell-free spent culture media, from both Lactobacillus species that had been grown with selenium dioxide for 48 h, showed enhanced antifungal activity against C. albicans. Enhanced antifungal activity of cell biomass against C. albicans was also observed in cultures grown with selenium dioxide. Selenium dioxide-treated Lactobacillus spp. or their cell-free spent broth inhibited the growth of C. albicans and should be investigated for possible use in anti-Candida probiotic formulations in future.

  20. The Extracellular Matrix of Candida albicans Biofilms Impairs Formation of Neutrophil Extracellular Traps.

    Directory of Open Access Journals (Sweden)

    Chad J Johnson

    2016-09-01

    Full Text Available Neutrophils release extracellular traps (NETs in response to planktonic C. albicans. These complexes composed of DNA, histones, and proteins inhibit Candida growth and dissemination. Considering the resilience of Candida biofilms to host defenses, we examined the neutrophil response to C. albicans during biofilm growth. In contrast to planktonic C. albicans, biofilms triggered negligible release of NETs. Time lapse imaging confirmed the impairment in NET release and revealed neutrophils adhering to hyphae and migrating on the biofilm. NET inhibition depended on an intact extracellular biofilm matrix as physical or genetic disruption of this component resulted in NET release. Biofilm inhibition of NETosis could not be overcome by protein kinase C activation via phorbol myristate acetate (PMA and was associated with suppression of neutrophil reactive oxygen species (ROS production. The degree of impaired NET release correlated with resistance to neutrophil attack. The clinical relevance of the role for extracellular matrix in diminishing NET production was corroborated in vivo using a rat catheter model. The C. albicans pmr1Δ/Δ, defective in production of matrix mannan, appeared to elicit a greater abundance of NETs by scanning electron microscopy imaging, which correlated with a decreased fungal burden. Together, these findings show that C. albicans biofilms impair neutrophil response through an inhibitory pathway induced by the extracellular matrix.

  1. Adaptations in the wall proteome of the clinical fungus Candida albicans in response to infection-related environmental conditions

    NARCIS (Netherlands)

    Sosińska, G.J.

    2012-01-01

    De pathogene schimmel Candida albicans past zijn celwandproteoom voortdurend aan aan uiteenlopende omgevingsomstandigheden die het aantreft in de gastheer. Dat levert sterke aanwijzingen op voor nieuwe aangrijpingspunten voor antischimmelmiddelen en voor nieuwe vaccinkandidaten. Dat blijkt uit

  2. Differential adherence and expression of virulence traits by Candida albicans and Candida parapsilosis in mono- and dual-species cultures in artificial saliva.

    Science.gov (United States)

    Seabra, C L; Botelho, C M; Henriques, M; Oliveira, R

    2013-08-01

    To evaluate specific virulence factors of Candida albicans and Candida parapsilosis clinical oral isolates in mono- and dual-species culture in the presence of artificial saliva. Two of the strains used in this study were isolated from co-infection (C. albicans AM and C. parapsilosis AM2), and the other two were isolated from single infection (C. albicans AC and C. parapsilosis AD). The number of adhered yeast cells was measured and their enzymatic activity was determined simultaneously. In mono-species culture, C. parapsilosis strains adhered to a higher extent to the surface in comparison with the C. albicans strains. In dual-species culture, the C. parapsilosis strains adhered more in the presence of C. albicans AM. Interestingly, C. albicans AM and C. parapsilosis AD adhered to a higher extent when compared with all other co-cultures. In dual-species culture, the enzymatic activity of C. parapsilosis strains in the presence of C. albicans AC was higher than in the presence of C. albicans AM. The virulence factors of C. albicans and C. parapsilosis differ from strain to strain and are influenced by the presence of other species in culture. To understand the expression of virulence factors in Candida dual-species systems.

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

    Science.gov (United States)

    O'Connor, Leanne; Caplice, Nicole; Coleman, David C; Sullivan, Derek J; Moran, Gary P

    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.

  4. 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.

  5. Ocorrência de Candida albicans em intestinos de bovinos

    Directory of Open Access Journals (Sweden)

    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.

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

    African Journals Online (AJOL)

    2016-06-24

    Jun 24, 2016 ... the use of glass ionomer restorative cements and amalgam to reduce C. albicans adhesion to .... each sample. The entire operation was carried out under aseptic conditions in duplicate. Statistical analysis. A multiple significance test with the Duncan correction .... glass fiber composite used in dentures.

  7. 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; Koo, Hyun; Kopycka-Kedzierawski, Dorota T

    2016-01-01

    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. 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. 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 (pseverity (pchildren were 1.3 ± 4.5 x104 cfu/ml and 1.2 ± 3.5 x104 cfu/ml (~3-log higher vs. caries-free children). Among 18 child-mother pairs, >60% of them demonstrated identical C. albicans REAG-B pattern. C. albicans isolated from >65% of child

  8. In vitro synergistic activity of lidocaine and miconazole against Candida albicans

    Directory of Open Access Journals (Sweden)

    Maria da Conceição dos Santos Oliveira Cunha

    2017-08-01

    Full Text Available Candida albicans is the main yeast isolated from vulvovaginal candidiasis(VVC and a major antifungal used to treat VVC is miconazole (MZ, it shows local toxic effects, such as irritation and burns. The lidocaine (LD is a local anesthetic. The aim of this study was to evaluate the synergistic activity of LD/MZ against 19 strains of C. albicans isolated from vaginal secretion. 78.9% of the strains were susceptible to the combination LD/MZ, demonstrating synergism of drugs. These drugs can be used to produce vaginal creams to treat VVC, especially drug resistant.

  9. Comparative Analysis of Protein Glycosylation Pathways in Humans and the Fungal Pathogen Candida albicans

    Directory of Open Access Journals (Sweden)

    Iván Martínez-Duncker

    2014-01-01

    Full Text Available Protein glycosylation pathways are present in all kingdoms of life and are metabolic pathways found in all the life kingdoms. Despite sharing commonalities in their synthesis, glycans attached to glycoproteins have species-specific structures generated by the presence of different sets of enzymes and acceptor substrates in each organism. In this review, we present a comparative analysis of the main glycosylation pathways shared by humans and the fungal pathogen Candida albicans: N-linked glycosylation, O-linked mannosylation and glycosylphosphatidylinositol-anchorage. The knowledge of similarities and divergences between these metabolic pathways could help find new pharmacological targets for C. albicans infection.

  10. The disruption of JEN1 from Candida albicans impairs the transport of lactate

    OpenAIRE

    Silva, Isabel Soares; Paiva, Sandra; Kötter, Peter; Entian, Karl-Dieter; Casal, Margarida

    2004-01-01

    A lactate permease was biochemically identified in Candida albicans RM1000 presenting the following kinetic parameters at pH 5.0: Km 0.33 ± 0.09 mM and Vmax 0.85± 0.06 nmol s-1 mg dry wt-1. Lactate uptake was competitively inhibited by pyruvic and propionic acids; acetic acid behaved as a non-competitive substrate. An ORF homologous to Saccharomyces cerevisiae gene JEN1 was identified (CaJEN1). Deletions of both CaJEN1 alleles of C. albicans (resulting strain CPK2) resulted in the loss of all...

  11. Dentinal Tubule Disinfection with Propolis & Two Extracts of Azadirachta indica Against Candida albicans Biofilm Formed on Tooth Substrate

    OpenAIRE

    Joy Sinha, Dakshita; Garg, Paridhi; Verma, Anurag; Malik, Vibha; Maccune, Edgar Richard; Vasudeva, Agrima

    2015-01-01

    Aim: This study evaluates the disinfection of dentinal tubules using Propolis, Azadirachta indica (alcoholic and aqueous extracts), 2% chlorhexidine gel and calcium hydroxide against Candida albicans biofilm formed on tooth substrate. Materials & Method: One hundred and five human teeth were infected with Candida albicans for 2 days. Samples were divided into 7 groups. Group I- Propolis, Group II- Alcoholic extract of Azadirachta indica, Group III- Aqueous extract of Azadirachta indica, Group...

  12. Prevalence of candida albicans in dental plaque and caries lesion of early childhood caries (ECC) according to sampling site.

    Science.gov (United States)

    Ghasempour, Maryam; Sefidgar, Seyed Ali Asghar; Eyzadian, Haniyeh; Gharakhani, Samaneh

    2011-01-01

    Candida albicans may have cariogenic potential but its role in caries etiology has not been established. The aim of this study was to determine candida albicans in supragingival dental plaque and infected dentine of cervical and proximal in early childhood caries (ECC). This cross-sectional study was carried out on 6o children aged 2-5 years, which were divided into 3 groups: children with at least one cervical caries; children with at least one proximal caries and caries-free. The infected dentine was collected from cervical and proximal caries lesions and plaque samples were collected from the three groups in order to compare the frequency of candida albicans in the collected sites. All samples were cultured in Sabouraud and CHROMagar medium and the cases that were positive for candida albicans were cultured in germ tube. Data were collected and analyzed. The mean age of the children was 3.9 years. From 100 samples, candida albicans samples were isolated in 55%, mold fungi were found in 29% cases and there was no fungal growth in 16% of the samples. In plaque samples, candida albicans were found in 15% of caries-free samples, 20% of the proximal and 80% of the cervical caries. In samples extracted from the caries, candida albicans were found in 60% of the proximal and 100% of the cervical caries. Mothers with university educational level had children with more cervical decays, caries free and proximal caries, respectively. The results showed that prevalence of Candida albicans in dental plaque and caries lesions of children with early childhood caries were relatively high and the prevalence was higher in cervical caries group.

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

    Science.gov (United States)

    Chin, Voon Kin; Lee, Tze Yan; Rusliza, Basir; Chong, Pei Pei

    2016-01-01

    Candida bloodstream infections remain the most frequent life-threatening fungal disease, with Candida albicans accounting for 70% to 80% of the Candida isolates recovered from infected patients. In nature, Candida species are part of the normal commensal flora in mammalian hosts. However, they can transform into pathogens once the host immune system is weakened or breached. More recently, mortality attributed to Candida infections has continued to increase due to both inherent and acquired drug resistance in Candida, the inefficacy of the available antifungal drugs, tedious diagnostic procedures, and a rising number of immunocompromised patients. Adoption of animal models, viz. minihosts, mice, and zebrafish, has brought us closer to unraveling the pathogenesis and complexity of Candida infection in human hosts, leading towards the discovery of biomarkers and identification of potential therapeutic agents. In addition, the advancement of omics technologies offers a holistic view of the Candida-host interaction in a non-targeted and non-biased manner. Hence, in this review, we seek to summarize past and present milestone findings on C. albicans virulence, adoption of animal models in the study of C. albicans infection, and the application of omics technologies in the study of Candida–host interaction. A profound understanding of the interaction between host defense and pathogenesis is imperative for better design of novel immunotherapeutic strategies in future. PMID:27763544

  14. Biofilm inhibition by Cymbopogon citratus and Syzygium aromaticum essential oils in the strains of Candida albicans.

    Science.gov (United States)

    Khan, Mohd Sajjad Ahmad; Ahmad, Iqbal

    2012-03-27

    Oils of Cymbopogon citratus and Syzygium aromaticum have been used in traditional medicine to treat fungal infections of skin, mouth, urinary and vaginal tract in Asian countries particularly India and other developing countries. To evaluate essential oils of Cymbopogon citratus and Syzygium aromaticum for their anti-biofilm activity against strong biofilm forming strains of Candida albicans. XTT reduction assay, Time kill assays, light microscopy and scanning electron microscopy (SEM) were employed to determine the effect of test oils on the Candida albicans biofilms. Most of the Candida albicans strains tested displayed formation of moderate to strong biofilms. Preformed Candida biofilms showed ≥1024 times increased resistance to antifungal drugs, 2 times to Syzygium aromaticum, but no increased tolerance for Cymbopogon citratus. Test oils were more active against preformed biofilms compared to amphotericin B and fluconazole. At 0.5× MIC, Cymbopogon citratus followed by Syzygium aromaticum were most inhibitory against biofilm formation. Light and electron microscopic studies revealed the deformity of three dimensional structures of biofilms formed in the presence of sub-MICs of Cymbopogon citratus. The cell membranes appeared to be the target site of compounds in sessile cells as displayed by SEM observations. Our data had demonstrated promising in vitro anti-biofilm activity by Cymbopogon citratus and Syzygium aromaticum and confirm the ethnopharmacological use of these oils in muco-cutaneous Candida infections. Furthermore, it suggests exploitation of these oils as new anti-biofilm products to deal with the problem of drug-resistance and recurrent infection associated with biofilm mode of growth of Candida spp. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  15. Alcohol and tobacco consumption affect the oral carriage of Candida albicans and mutans streptococci.

    Science.gov (United States)

    Sheth, C C; Makda, K; Dilmahomed, Z; González, R; Luzi, A; Jovani-Sancho, M Del M; Veses, V

    2016-10-01

    This study sought to determine if there is a relationship between the consumption of alcohol and tobacco and oral colonization by mutans streptococci and Candida species. Subjects were recruited from the University Dental Clinic of CEU Cardenal Herrera University (Moncada, Valencia). Information on alcohol and tobacco consumption was obtained by questionnaire. Individual stimulated saliva samples from 105 patients were obtained and selective media was used to isolate and quantify mutans streptococci and Candida spp. colony forming units per millilitre of saliva (CFU ml(-1) ). Samples were stratified by duration and quantity of alcohol and tobacco consumption. Alcohol consumption statistically significantly decreased oral carriage of mutans streptococci, whereas there was no effect on Candida albicans colonization levels. Tobacco users were found to harbour elevated levels of C. albicans; however, there was no observed effect on bacterial colonization by mutans streptococci. The carriage of other species investigated, such as Candida krusei, Candida tropicalis and lactobacilli, do not show a response to the consumption of the stimulants analysed. Microbial colonization of the oral cavity changes in a species-specific manner in response to dietary and social habits such as drinking alcohol and smoking. In this paper, we evaluate the effect of alcohol and tobacco consumption on key species of the oral microflora. Our results show species-specific changes in two major opportunistic pathogens, such as Candida albicans and mutans streptococci, whereas other members of oral microflora are not affected by the consumption of the stimulants studied. We believe this original paper will contribute to raise awareness among the dental community towards a more personalized oral health assessment, taking in consideration alcohol and tobacco consumption in the prevention of specific oral and systemic pathologies. © 2016 The Society for Applied Microbiology.

  16. 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. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  17. Evaluation of fluorescence in situ hybridisation (FISH) for the identification of Candida albicans in comparison with three phenotypic methods.

    Science.gov (United States)

    Lakner, Anna; Essig, Andreas; Frickmann, Hagen; Poppert, Sven

    2012-05-01

    Severe Candida infections are increasing and are associated with considerable morbidity and mortality. Rapid and accurate differentiation of Candida albicans from non-C. albicans species is essential for therapeutic decisions. We therefore developed a fluorescence in situ hybridisation (FISH) assay comprising previously described probes and a newly designed specific C. albicans probe/competitor probe combination. The FISH probes were first evaluated using 99 selected fungal strains covering 31 species, and a specificity between 96% and 100% and a sensitivity of 100%. The FISH assay was then applied to 110 clinical isolates in parallel with API32C, the chromogenic Candida ID agar, and determination of filamentous colony morphology. All tests produced highly reliable results. However, the Candida ID agar misidentified Candida dubliniensis as C. albicans. Determination of filamentous colony morphology allowed 100% reliable identification of C. albicans, but took 48 h. FISH allowed identification of clinical C. albicans isolates within 3 h with a sensitivity and specificity of 100%. FISH was additionally applied to 48 blood cultures showing yeasts in the Gram stain and correctly identified all 33 cases of C. albicans. © 2011 Blackwell Verlag GmbH.

  18. Novel role of a family of major facilitator transporters in biofilm development and virulence of Candida albicans.

    Science.gov (United States)

    Shah, Abdul Haseeb; Singh, Ashutosh; Dhamgaye, Sanjiveeni; Chauhan, Neeraj; Vandeputte, Patrick; Suneetha, Korivi Jyothiraj; Kaur, Rupinder; Mukherjee, Pranab K; Chandra, Jyotsna; Ghannoum, Mahmoud A; Sanglard, Dominique; Goswami, Shyamal K; Prasad, Rajendra

    2014-06-01

    The QDR (quinidine drug resistance) family of genes encodes transporters belonging to the MFS (major facilitator superfamily) of proteins. We show that QDR transporters, which are localized to the plasma membrane, do not play a role in drug transport. Hence, null mutants of QDR1, QDR2 and QDR3 display no alterations in susceptibility to azoles, polyenes, echinocandins, polyamines or quinolines, or to cell wall inhibitors and many other stresses. However, the deletion of QDR genes, individually or collectively, led to defects in biofilm architecture and thickness. Interestingly, QDR-lacking strains also displayed attenuated virulence, but the strongest effect was observed with qdr2∆, qdr3∆ and in qdr1/2/3∆ strains. Notably, the attenuated virulence and biofilm defects could be reversed upon reintegration of QDR genes. Transcripts profiling confirmed differential expression of many biofilm and virulence-related genes in the deletion strains as compared with wild-type Candida albicans cells. Furthermore, lipidomic analysis of QDR-deletion mutants suggests massive remodelling of lipids, which may affect cell signalling, leading to the defect in biofilm development and attenuation of virulence. In summary, the results of the present study show that QDR paralogues encoding MFS antiporters do not display conserved functional linkage as drug transporters and perform functions that significantly affect the virulence of C. albicans.

  19. Functional genomic analysis of the response to hypoxic and oxidative stress in Candida albicans

    OpenAIRE

    Miguel Blanco, Ana

    2017-01-01

    Candida albicans es el patógeno humano más prevalente. A pesar de ser un organismo comensal, también es un hongo oportunista que puede causar infecciones de seria gravedad en personas inmunodeprimidas. Aunque los principales factores de virulencia han sido caracterizados, el proceso exacto de patogénesis en Candida todavía se desconoce. Los mecanismos de adaptación a los distintos ambientes a los que se enfrenta durante la invasión del cuerpo humano todavía no están suficientemente caracteriz...

  20. Characterising atypical Candida albicans clinical isolates from six third-level hospitals in Bogotá, Colombia.

    Science.gov (United States)

    Rodríguez-Leguizamón, Giovanni; Fiori, Alessandro; López, Luisa F; Gómez, Beatriz L; Parra-Giraldo, Claudia M; Gómez-López, Arley; Suárez, Carlos F; Ceballos, Andrés; Van Dijck, Patrick; Patarroyo, Manuel A

    2015-10-05

    Candida species are the most frequently found fungal pathogens causing nosocomial disease in a hospital setting. Such species must be correctly identified to ensure that appropriate control measures are taken and that suitable treatment is given for each species. Candida albicans is causing most fungal disease burden worldwide; the challenge lies in differentiating it from emerging atypical, minor and related species such as Candida dubliniensis and Candida africana. The purpose of this study was to compare identification based on MALDI-TOF MS to standard identification systems using a set of nosocomial isolates. Eleven nosocomial samples were collected from 6 third-level hospitals in Bogotá, Colombia. All the samples were identified by combining MALDI-TOF MS with morphological characters, carbohydrate assimilation and molecular markers (D1/D2 and HWP1). The present work describes the first collection of atypical Colombian Candida clinical isolates; these were identified as Candida albicans/Candida africana by their MALDI-TOF MS profile. Phenotypical characteristics showed that they were unable to produce chlamydospores, assimilate trehalose, glucosamine, N- acetyl-glucosamine and barely grew at 42 °C, as would be expected for Candida africana. The molecular identification of the D1/D2 region of large subunit ribosomal RNA and HWP1 hyphal cell wall protein 1 sequences from these isolates was consistent with those for Candida albicans. The mass spectra obtained by MALDI-TOF MS were analysed by multi-dimensional scaling (MDS) and cluster analysis, differences being revealed between Candida albicans, Candida africana, Candida dubliniensis reference spectra and two clinical isolate groups which clustered according to the clinical setting, one of them being clearly related to C. albicans. This study highlights the importance of using MALDI-TOF MS in combination with morphology, substrate assimilation and molecular markers for characterising Candida albicans

  1. The Mkk2 MAPKK Regulates Cell Wall Biogenesis in Cooperation with the Cek1-Pathway in Candida albicans

    NARCIS (Netherlands)

    Román, Elvira; Alonso-Monge, Rebeca; Miranda Bedate, A.|info:eu-repo/dai/nl/413292614; Pla, Jesús

    2015-01-01

    The cell wall integrity pathway (CWI) plays an important role in the biogenesis of the cell wall in Candida albicans and other fungi. In the present work, the C. albicans MKK2 gene that encodes the putative MAPKK of this pathway was deleted in different backgrounds and the phenotypes of the

  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. Novel structural features in Candida albicans hyphal glucan provide a basis for differential innate immune recognition of hyphae versus yeast

    NARCIS (Netherlands)

    Lowman, D.W.; Greene, R.R.; Bearden, D.W.; Kruppa, M.D.; Pottier, M.; Monteiro, M.A.; Soldatov, D.V.; Ensley, H.E.; Cheng, S.C.; Netea, M.G.; Williams, D.L.

    2014-01-01

    The innate immune system differentially recognizes Candida albicans yeast and hyphae. It is not clear how the innate immune system effectively discriminates between yeast and hyphal forms of C. albicans. Glucans are major components of the fungal cell wall and key fungal pathogen-associated

  4. 1,25-dihydroxyvitamin D3 modulates cytokine production induced by Candida albicans: impact of seasonal variation of immune responses

    NARCIS (Netherlands)

    Khoo, A.L.; Chai, L.; Koenen, H.J.P.M.; Kullberg, B.J.; Joosten, I.; Ven, A.J.A.M. van der; Netea, M.G.

    2011-01-01

    BACKGROUND: Our interest in immunological effects produced by vitamin D(3) (1,25(OH)(2)D(3)) and its therapeutic potential prompted us to examine the role of 1,25(OH)(2)D(3) on cytokine production by Candida albicans. METHODS: Peripheral blood mononuclear cells (PBMC) with stimulated C. albicans and

  5. 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

  6. Hypoxic conditions and iron restriction affect the cell-wall proteome of Candida albicans grown under vagina-simulative conditions

    NARCIS (Netherlands)

    Sosinska, Grazyna J.; de Groot, Piet W. J.; Teixeira de Mattos, M. Joost; Dekker, Henk L.; de Koster, Chris G.; Hellingwerf, Klaas J.; Klis, Frans M.

    2008-01-01

    Proteins that are covalently linked to the skeletal polysaccharides of the cell wall of Candida albicans play a major role in the colonization of the vaginal mucosal surface, which may result in vaginitis. Here we report on the variability of the cell-wall proteome of C. albicans as a function of

  7. Co-Occurrence of Candida albicans and Staphylococcus aureus in ...

    African Journals Online (AJOL)

    The aim of this study was to investigate the prevalence of Candida and Staphylococcus spp. in the nasal cavity of apparently healthy university students. Eighty-six (86) nasal samples from apparently healthy undergraduate students of Ambrose Alli University, Ekpoma were screened with Mannitol agar and Sabrourand's ...

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

    Directory of Open Access Journals (Sweden)

    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.

  9. 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

  10. 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

    2015-01-01

    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

  11. Ekstrak Buah Kaktus Pir Berduri Menghambat Pertumbuhan Staphy-lococcus Aureus,Streptococcus Mutans, Dan Candida Albicans

    OpenAIRE

    Irene Edith Riuwpassa, Dr.drg. M.Si

    2013-01-01

    Hal yang adapat disimpulkan adalah ekstrak buah kaktus pir berduri dapat menghambat pertumbuhan S.aureus, S.mutans, dan C.albicans. Semakin tinggi konsentrasi ekstrak maka semakin berkurang pertumbuhan koloni S.aureus, S.mutans, dan C.albicans, begitu juga sebaliknya. penelitian dimaksudkan untuk mengetahui pengaruh ekstrakl kaktus pir berduri dalam menghambat pertumbuhan bakteri strahylococcus aureus, Streptococcus mutans, dan candida albicans.

  12. Als3 Is a Candida albicans Invasin That Binds to Cadherins and Induces Endocytosis by Host Cells

    OpenAIRE

    Phan, Quynh T.; Myers, Carter L.; Yue Fu; Sheppard, Donald C.; Yeaman, Michael R.; Welch, William H.; Ibrahim, Ashraf S.; Edwards, John E.; Filler, Scott G.

    2007-01-01

    Candida albicans is the most common cause of hematogenously disseminated and oropharyngeal candidiasis. Both of these diseases are characterized by fungal invasion of host cells. Previously, we have found that C. albicans hyphae invade endothelial cells and oral epithelial cells in vitro by inducing their own endocytosis. Therefore, we set out to identify the fungal surface protein and host cell receptors that mediate this process. We found that the C. albicans Als3 is required for the organi...

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    Vauchelles, Romain; Stalder, Danièle; Botton, Thomas; Arkowitz, Robert A; Bassilana, Martine

    2010-10-28

    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.

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

    Science.gov (United States)

    Manoharan, Ranjith Kumar; Lee, Jin-Hyung; Lee, Jintae

    2017-01-01

    Candida albicans can form biofilms composed of yeast, hyphal, and pseudohyphal elements, and C. albicans cells in the hyphal stage could be a virulence factor. The present study describes the chemical composition, antibiofilm, and antihyphal activities of cedar leaf essential oil (CLEO), which was found to possess remarkable antibiofilm activity against C. albicans but not to affect its planktonic cell growth. Nineteen components were identified in CLEO by gas chromatography/mass spectrometry, and phenolics were the main constituents. Of these, camphor, fenchone, fenchyl alcohol, α-thujone, and borneol significantly reduced C. albicans biofilm formation. Notably, treatments with CLEO, camphor, or fenchyl alcohol at 0.01% clearly inhibited hyphal formation, and this inhibition appeared to be largely responsible for their antibiofilm effects. Transcriptomic analyses indicated that camphor and fenchyl alcohol downregulated some hypha-specific and biofilm related genes (ECE1, ECE2, RBT1, and EED1). Furthermore, camphor and fenchyl alcohol reduced C. albicans virulence in a Caenorhabditis elegans nematode model. These results demonstrate CLEO, camphor, and fenchyl alcohol might be useful for controlling C. albicans infections. PMID:28824600

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

    Directory of Open Access Journals (Sweden)

    Ranjith Kumar Manoharan

    2017-08-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

  18. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. The role of Candida albicans in the severity of multiple sclerosis.

    Science.gov (United States)

    Saroukolaei, Shahla Amri; Ghabaee, Mojdeh; Shokri, Hojjatollah; Badiei, Alireza; Ghourchian, Shadi

    2016-11-01

    The purpose of this study was to compare the specific activity of proteinase A in Candida albicans (C. albicans) between multiple sclerosis (MS) patients and controls. A total of 135 and 100 C. albicans strains were isolated from superficial surfaces of MS patients and healthy controls. Analytical models (regression and neural network) were applied to predict the severity of MS considering specific enzyme activity (SEA) and other factors which affect the expanded disability status scale (EDSS). The SEA of C. albicans in MS patients (3466.95 ± 277.25 μmol min-1 mg-1 ) was significantly more than that of healthy controls (1108.98 ± 294.51 μmol min-1 mg-1 ) that was confirmed by regression model (P albicans in MS patients was significantly more than the healthy controls. The results suggest that the level of SEA of proteinase A and probably the capacity of C. albicans isolates to invade the host tissue is associated with the severity of MS. © 2016 Blackwell Verlag GmbH.