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Candida glabrata Pwp7p and Aed1p are required for adherence to human endothelial cells.

ABSTRACT: Candida glabrata owes its success as a pathogen, in part, to a large repertoire of adhesins present on the cell surface. Our current knowledge of C. glabrata adhesins and their role in the interaction between host and pathogen is limited to work with only a single family of epithelial adhesins (Epa proteins). Here, we report on the identification and characterization of a family of glycosylphosphatidylinositol-anchored cell wall proteins in C. glabrata. These proteins are absent in both Saccharomyces cerevisiae and Candida albicans, suggesting that C. glabrata has evolved different mechanism(s) for interaction with host cells. In the current study, we present data on the characterization of Pwp7p (PA14 domain containing Wall Protein) and Aed1p (Adherence to Endothelial cells) of this family in the interaction of C. glabrata with human umbilical vein endothelial cells. The deletion of C. glabrata genes PWP7 and AED1 results in a significant reduction in adherence to endothelial cells compared with the wild-type parent. These data indicate that C. glabrata utilizes these proteins for adherence to endothelial cells in vitro.

SUBMITTER: Desai C

PROVIDER: S-EPMC3202042 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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Candida glabrata Pwp7p and Aed1p are required for adherence to human endothelial cells.

Desai Chirayu C Mavrianos John J Chauhan Neeraj N

FEMS yeast research 20110729 7

Candida glabrata owes its success as a pathogen, in part, to a large repertoire of adhesins present on the cell surface. Our current knowledge of C. glabrata adhesins and their role in the interaction between host and pathogen is limited to work with only a single family of epithelial adhesins (Epa proteins). Here, we report on the identification and characterization of a family of glycosylphosphatidylinositol-anchored cell wall proteins in C. glabrata. These proteins are absent in both Saccharo ...[more]

PMID: 21726406

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Project description:The opportunistic pathogen Candida glabrata is the second most frequent causative agent of vulvovaginal candidiasis (VVC), a disease that affects 70-75% of women at least once during their life. However, C. glabrata is almost avirulent in mice and normally incapable of inflicting damage to vaginal epithelial cells in vitro. We thus proposed that host factors present in vivo may influence C. glabrata pathogenicity. We, therefore, analyzed the impact of albumin, one of the most abundant proteins of the vaginal fluid. The presence of human, but not murine, albumin dramatically increased the potential of C. glabrata to damage vaginal epithelial cells. This effect depended on macropinocytosis-mediated epithelial uptake of albumin and subsequent proteolytic processing. The enhanced pathogenicity of C. glabrata can be explained by a combination of beneficial effects for the fungus, which includes an increased access to iron, accelerated growth, and increased adhesion. Screening of C. glabrata deletion mutants revealed that Hap5, a key regulator of iron homeostasis, is essential for the albumin-augmented damage potential. The albumin-augmented pathogenicity was reversed by the addition of iron chelators and a similar increase in pathogenicity was shown by increasing the iron availability, confirming a key role of iron. Accelerated growth not only led to higher cell numbers, but also to increased fungal metabolic activity and oxidative stress resistance. Finally, the albumin-driven enhanced damage potential was associated with the expression of distinct C. glabrata virulence genes. Transcriptional responses of the epithelial cells suggested an unfolded protein response (UPR) and ER-stress responses combined with glucose starvation induced by fast growing C. glabrata cells as potential mechanisms by which cytotoxicity is mediated.Collectively, we demonstrate that albumin augments the pathogenic potential of C. glabrata during interaction with vaginal epithelial cells. This suggests a role for albumin as a key player in the pathogenesis of VVC.

Dataset Information

Candida glabrata Pwp7p and Aed1p are required for adherence to human endothelial cells.

Publications

Candida glabrata Pwp7p and Aed1p are required for adherence to human endothelial cells.

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