Saccharomyces Killer Yeasts to Combat Fungal Human Pathogens
Faculty Mentor Information
Paul A Rowley, University of Idaho
Abstract
Recurring vulvovaginal and oropharyngeal thrush, fungal sepsis, and some forms of meningitis are all caused by pathogenic species of yeast. Rising levels of drug resistance in clinical yeast isolates indicate a need for the development of new antifungal drugs. We have found that Saccharomyces “killer” yeasts, which produce antifungal toxins, can inhibit the growth of human pathogens such as Candida spp. and Cryptococcus spp. with a high level of specificity. Our goal is to characterize these Saccharomyces killer toxins. We expect that the variation in yeast-killing ability across toxins is linked to their primary genetic sequences. Because killer toxins are often encoded by double-stranded RNA viruses, we have purified RNAs from killer yeasts and determined their genetic sequences using next generation sequencing. We have cloned these toxin genes into artificial plasmid vectors for expression within a non-killer laboratory strain of S. cerevisiae to test their functionality. We will relate changes in killer toxin activity to the genetic sequence of the toxin genes. The sequencing and screening of Saccharomyces killer toxins will build a greater understanding of how to use these potent antifungal proteins against fungal pathogens of humans.
Saccharomyces Killer Yeasts to Combat Fungal Human Pathogens
Recurring vulvovaginal and oropharyngeal thrush, fungal sepsis, and some forms of meningitis are all caused by pathogenic species of yeast. Rising levels of drug resistance in clinical yeast isolates indicate a need for the development of new antifungal drugs. We have found that Saccharomyces “killer” yeasts, which produce antifungal toxins, can inhibit the growth of human pathogens such as Candida spp. and Cryptococcus spp. with a high level of specificity. Our goal is to characterize these Saccharomyces killer toxins. We expect that the variation in yeast-killing ability across toxins is linked to their primary genetic sequences. Because killer toxins are often encoded by double-stranded RNA viruses, we have purified RNAs from killer yeasts and determined their genetic sequences using next generation sequencing. We have cloned these toxin genes into artificial plasmid vectors for expression within a non-killer laboratory strain of S. cerevisiae to test their functionality. We will relate changes in killer toxin activity to the genetic sequence of the toxin genes. The sequencing and screening of Saccharomyces killer toxins will build a greater understanding of how to use these potent antifungal proteins against fungal pathogens of humans.