Influence of CgPDR1 hyperactivity on the expression of EPA-family adhesins in Candida glabrata

Candida glabrata is an emerging opportunistic pathogen that is known to develop resistance to azole drugs due to increased drug efflux. Resistance is mediated by a range of gain-of-function (GOF) mutations in CgPDR1, which are also known to enhance virulence. Recent data suggests that increased adherence to epithelial cells is partially responsible for the gained virulence, however it remains unclear which genes are implicated. In this study we used Real-Time quantitative PCR to analyze the influence of CgPDR1 GOF mutations on the expression of several cell wall proteins that are either known or predicted to play a role in the adhesion of yeast to host epithelial cells. CgPDR1 GOF mutations lead to an overexpression of different adhesins. While the adhesins were not regulated in a homogenous fashion for all the studied strains, we observed that EPA1 played a prominent role being often up regulated as the only adhesin. An included non-subtelomerically located adhesin did not show any change in expression levels in GOF mutant strains compared to the wild type strain. Our findings point towards a complex regulation of adhesin expression through CgPDR1, implicating subtelomeric-silencing mechanisms. These processes could lead to enhanced adherence to host cells and thereby contribute to the observed gain in virulence in CgPDR1 mutants