Inhibition of Drug-Resistant Candida glabrata by Killer Toxins Produced by Saccharomyces cerevisiae

Combatting the spread of drug-resistant microbes requires new antifungal compounds with novel mechanisms of inhibition. Our lab investigates natural, proteinaceous toxins that are coded by double stranded RNA satellites found within Saccharomyces cerevisiae. Commonly known as “killer yeasts”, toxin-producing strains of S. cerevisiae have been found to inhibit the growth of many important fungal pathogens. To assess the value of killer yeasts for medical application we tested over 6,000 interactions between killer yeasts and various important fungal pathogens. To determine the susceptibility of fungi to killer toxins, we competed killer yeasts against a dilute lawn of a fungal pathogen; an active toxin produces a zone of growth inhibition in the lawn around the killer yeast. We determined that Candida glabratais broadly susceptible to killer toxins, while other Candida species showed little or no susceptibility. Of the 90 strains of S. cerevisiae tested against C. glabrata seven were capable of inhibiting all clinical strains of drug-resistant C. glabrata available from the Center for Disease Control and the U.S. Department of Agriculture. In our evaluation of these toxins as potential antifungal therapeutics we confirmed their inhibitory capability against C. glabrata under physiological conditions. Based on the results of these tests and prior knowledge about killer yeasts, we believe that these toxins show a potential as antifungal therapeutic precursors to treat recalcitrant infections caused by C. glabrata.