Exploring Antifungal Drugs Produced by Brewer's Yeasts
Additional Funding Sources
The project described was supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under Grant #P20GM103408.
Abstract
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 the brewer’s yeast, Saccharomyces cerevisiae. Commonly known as killer yeasts, toxin-producing strains of S. cerevisiae have been found to inhibit the growth of many fungal pathogens. We have found that Candida glabrata is 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 CDC as well as the Wayne State Medical Clinic. In our evaluation of these toxins as potential antifungal therapeutics we confirmed their inhibitory capability against C. glabrata under physiological conditions. We have also explored how C. glabrata develops resistance to killer toxins. We developed a protocol for generating and isolating resistant mutants which we then characterized growth rate and levels of resistance. 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 for drug resistant fungal infections.
Exploring Antifungal Drugs Produced by Brewer's Yeasts
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 the brewer’s yeast, Saccharomyces cerevisiae. Commonly known as killer yeasts, toxin-producing strains of S. cerevisiae have been found to inhibit the growth of many fungal pathogens. We have found that Candida glabrata is 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 CDC as well as the Wayne State Medical Clinic. In our evaluation of these toxins as potential antifungal therapeutics we confirmed their inhibitory capability against C. glabrata under physiological conditions. We have also explored how C. glabrata develops resistance to killer toxins. We developed a protocol for generating and isolating resistant mutants which we then characterized growth rate and levels of resistance. 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 for drug resistant fungal infections.
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