Abstract
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.IMPORTANCECandida 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.
Highlights
IMPORTANCE Candida glabrata cell wall proteins mediate the attachment of C. glabrata to abiotic surfaces through molecular interactions that are poorly understood
We show that three major Epa proteins (Epa1, Epa6, and Epa7) contribute strongly to hydrophilic and hydrophobic adhesion
We wished to study the adherence of C. glabrata cells to hydrophilic and hydrophobic surfaces, which represents the first step of biofilm msphere.asm.org 2
Summary
IMPORTANCE Candida glabrata cell wall proteins mediate the attachment of C. glabrata to abiotic surfaces through molecular interactions that are poorly understood. Mutants that disrupt subtelomeric silencing show increased biofilm production; second, EPA6 mutants are substantially compromised for biofilm formation [26] In addition to these genetic studies, a previous biophysical analysis documented a strong adhesion of C. glabrata to hydrophobic surfaces and showed that much of that adhesion was mediated by the Epa adhesin [27]. These data suggest substantial overlap in the regulation of host cell adherence and the regulation of biofilm formation on abiotic surfaces and implicate subtelomeric genes, including some cell wall proteins and Epa, in that process. How subtelomeric silencing impacts the expression of cell surface proteins and how that impacts C. glabrata adherence to abiotic surfaces remain to be fully explored
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