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Yeast Antifungal Proteins for Inhibiting Candida glabrata

OTT Case 19-010 | Patent Pending

The current emergence of drug-resistant fungal pathogens and the cytotoxic side effects of existing antifungal therapeutics pose a challenge to reducing mortality rates of invasive fungal diseases. “Killer yeasts” can inhibit the growth of fungal pathogens by producing protein fungicides called “killer toxins.”

Killer toxin production by the yeast Saccharomyces cerevisiae is most often dependent on infection by mycoviruses and the presence of cytoplasmic double-stranded RNA (dsRNA) satellites. It was hypothesized that dsRNAs isolated from S. cerevisiae would be a source of novel antifungal proteins that are biologically active against human pathogenic fungi.

Strains of Saccharomyces yeasts were screened for production of killer toxins using in vitro agar plate-based assays. A subset of the killer yeasts identified were found to be biologically active against human-pathogenic yeasts. A screening of this subset of killer yeasts against C. glabrata revealed that the killer toxins K1 and K2 expressing yeasts were broadly antifungal to all 26 clinical strains of C. glabrata provided by the Center of Disease Control and the Food and Drug Administration Antimicrobial Resistance Isolate Bank and 27 environmental and clinical strains provided by the Agricultural Research Service Culture Collection (Northern Regional Research Laboratory). Importantly, killer yeasts are effective at inhibiting the growth of clinically isolated C. glabrata that have a resistance to common therapeutic antifungal drugs including azoles, echinocandins, and flucytosine.