Atomic Force Microscopy Demonstrates that Candida glabrata Uses Three Epa Proteins To Mediate Adhesion to Abiotic Surfaces

Abstract

Candida glabrata cell wall proteins mediate the attachment of C. glabrata to abiotic surfaces through molecular interactions that are poorly understood. Here, we study the forces engaged in Epa-dependent adhesion using single-cell techniques. Fungal adhesion to hydrophilic and hydrophobic substrates involves mainly three Epa proteins, suggesting a broad role for the Epa adhesins in mediating adherence. These proteins might represent a potential target for the development of innovative antifungal drugs. The fungal pathogen Candida glabrata can cause both mucosal and disseminated infections. Cell adhesion, a key step in colonization and infection, depends in C. glabrata primarily on the Epa family of cell adhesion proteins. While Epa proteins have been documented to mediate specific adhesion to host glycans, some of them also promote nonspecific adhesion to abiotic surfaces, though this is incompletely understood. Here we address this issue using a combination of genetics and single-cell force measurements. By quantifying the forces driving the attachment of single C. glabrata cells to hydrophobic and hydrophilic substrates, we show that cell adhesion is strongly increased by loss of Sir-mediated silencing. Using a series of mutant strains lacking specific EPA genes, we demonstrate unexpectedly that three major Epa proteins, Epa1, Epa6, and Epa7, primarily contribute to both hydrophilic and hydrophobic interactions, suggesting a broad role for the Epa adhesins in mediating specific and nonspecific adherence and implicating Epa genes in biofilm formation on abiotic surfaces. IMPORTANCE Candida glabrata cell wall proteins mediate the attachment of C. glabrata to abiotic surfaces through molecular interactions that are poorly understood. Here, we study the forces engaged in Epa-dependent adhesion using single-cell techniques. Fungal adhesion to hydrophilic and hydrophobic substrates involves mainly three Epa proteins, suggesting a broad role for the Epa adhesins in mediating adherence. These proteins might represent a potential target for the development of innovative antifungal drugs.