Sensitivity and Resistance to “Killer toxins” in Yeast

1.5 million people die annually from infections caused by pathogenic fungi. Alarmingly, these fungi are developing resistance to antifungal treatments, galvanizing the renewed search for new types of antifungal treatment. A possible new treatment could be the potent antifungal “killer” toxins produced by yeasts, however, some fungi are naturally resistant to these toxins. My project aims to identify the strain-specific differences found within Saccharomyces cerevisiae that are important for resistance and sensitivity to killer toxins. To identify genetic determinants of killer toxin susceptibility, I will transform a strain of S. cerevisiae that is resistant to the K1 killer toxin (strain UWOPS 83-78) with a library of plasmids that contain genome fragments from a killer toxin sensitive strain of S. cerevisiae. I will look for changes in killer toxin susceptibility by screening thousands of colonies for sensitivity to the K1 killer toxin using an agar plate-based assay that I have developed. Knowing the genetic determinants of why certain strains of S. cerevisiae become resistant to killer toxins will help us understand how pathogenic fungi could develop resistance to killer toxins, how to prevent the fungi from developing resistance, and help us to better develop killer toxins that kill resistant pathogenic fungi