The EPA2 adhesin encoding gene is responsive to oxidative stress in the opportunistic fungal pathogen Candida glabrata
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Candida glabrata has emerged as an important opportunistic pathogen in both mucosal and bloodstream infections. C. glabrata contains 67 adhesin-like glycosylphosphatidylinositol-cell-wall proteins (GPI-CWPs), which are classified into seven groups and the largest is the Epa family. Epa proteins are very diverse and their expression is differentially regulated. Like many of the EPA genes, EPA2 is localized in a subtelomeric region where it is subject to chromatin-based transcriptional silencing and its role remains largely unexplored. In this study, we show that EPA2 gene is induced specifically in vitro in the presence of oxidative stress generated by H2O2. This induction is dependent on both Yap1 and Skn7, whereas Msn4 represses EPA2 expression. Interestingly, EPA2 is not induced during phagocytosis, but its expression can be identified in the liver in a murine model of systemic infection. Epa2 has no effect on the virulence of C. glabrata. The work presented herein provides a foundation for future studies to dissect the molecular mechanism(s) by which EPA2 of C. glabrata can be induced in the presence of oxidative stress in a region subject to subtelomeric silencing. © 2015, Springer-Verlag Berlin Heidelberg.
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EPA2; H2O2; IVET; Oxidative stress response; Silencing adhesin; EPA1 protein; EPA2 protein; gamma interferon; protein; purinergic P2X7 receptor; transcription factor; transcription factor Skn7; transcription factor Msn2; transcription factor Msn4; transcription factor Yap1; unclassified drug; cell adhesion molecule; fungal protein; hydrogen peroxide; transcription factor; animal cell; animal experiment; animal model; animal tissue; Article; Candida glabrata; candidiasis; cell division; cell surface; cell viability; controlled study; fungal virulence; in vitro study; in vivo study; macrophage; mouse; nonhuman; oxidative stress; phagocyte; phagocytosis; priority journal; promoter region; protein expression; respiratory burst; steady state; telomere; transcription initiation; transcription regulation; animal; Candida glabrata; candidiasis; chemistry; drug effects; gene expression regulation; gene silencing; genetics; liver; metabolism; microbiology; oxidative stress; pathogenicity; pathology; virulence; Animals; Candida glabrata; Candidiasis; Cell Adhesion Molecules; Fungal Proteins; Gene Expression Regulation, Fungal; Gene Silencing; Hydrogen Peroxide; Liver; Mice; Oxidative Stress; Phagocytosis; Telomere; Transcription Factors; Virulence
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