Secondary metabolites from food-derived yeasts inhibit virulence of Candida albicans

Beneficial microbes in the intestine are thought to control pathogen overgrowth by competing for limited nutrients. Our findings modify this prevailing paradigm of a passive, microbial antagonistic mode of action to an active, directed mechanism mediated by specific secondary metabolites. We describe two food-derived yeasts, Saccharomyces cerevisiae and Issatchenkia occidentalis, that inhibit virulence traits of Candida albicans, including hyphal morphogenesis, biofilms formation and adhesion to intestinal epithelial cells. These yeasts also protect the model host Caenorhabditis elegans from C. albicans infection. We demonstrate that the protective activity is primarily retained in the secretome of the beneficial yeasts and the protection they provide as a physical barrier is minimal. Mutant analysis demonstrates that phenylethanol and tryptophol are necessary for protection and experiments with commercially procured compounds indicates that they are sufficient to inhibit C. albicans virulence. We propose food-derived yeasts as an alternative or combination therapy to conventional antifungal therapy for C. albicans infection.