Secondary Metabolites from Food-Derived Yeasts Inhibit Virulence of Candida albicans

A sparse number of available antifungal drugs, therapeutic side effects, and drug resistance are major challenges in current antifungal therapy to treat Candida albicans-associated infections. Here, we describe two food-derived yeasts, Saccharomyces cerevisiae and Issatchenkia occidentalis, that inhibit virulence traits of C. albicans, including hyphal morphogenesis, biofilm 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 negligible. S. cerevisiae aro8 aro9 mutant analysis demonstrate that phenylethanol and tryptophol are necessary for protection, and experiments with commercially procured compounds indicate 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. IMPORTANCE The gut microbiome, primarily established by food, is complex and contributes to the health of the host. Molecular mechanisms that regulate microbial interactions and host health remain unclear. Here, we show that the pathogen C. albicans interacts with food-derived beneficial yeasts in the gut of the microscopic worm, C. elegans, forming a simple microbiome. C. albicans can colonize the worm gut, compromising the worm's health, and exposure to the food-derived yeasts ameliorates this effect protecting the nematode host. We identify small molecules from food-derived yeasts that are necessary and sufficient to inhibit multiple virulence traits of C. albicans and protect the nematode host. The nematode gut faithfully recapitulates a mammalian intestine. This could be an effective alternative or combination therapy for C. albicans infection.