Abstract Title
The Cell Membrane Protein Kre1 as a Receptor for the K1 Killer Toxin in Pathogenic Yeasts
Additional Funding Sources
The project described was supported by a student grant from the UI Office of Undergraduate Research.
Abstract
Killer yeasts are single-celled members of the Fungal kingdom that have the ability to create antifungal proteins called killer toxins. These killer toxins compete with other yeasts in their environment to inhibit growth and kill fungal cells. Due to these functions, killer yeasts are studied for their biomedical potential. Statistically speaking,1 in 3 women will get a yeast infection at one point in their lives. To treat vaginal yeast infections, azoles are the most commonly prescribed class of drugs, and are thought to be as much as 32% ineffective for treating these infections. Candida glabrata is a yeast responsible for vulvovaginal candidiasis and is highly susceptible to a killer toxin named K1, produced by baker’s yeast (Saccharomyces cerevisiae). Kre1 is believed to be the secondary cell receptor for K1, potentially playing a role in yeast cell sensitivity. I hypothesize that Kre1 is the primary determinant of K1 sensitivity in diverse Ascomycota yeasts. This hypothesis is supported by findings from Breinig et al., among others, as their research found kre1Δ cells are completely resistant to K1, and expression of KRE1 restored sensitivity. I will be further testing this hypothesis by extracting, cloning, and modifying KRE1s from a variety of Candida yeasts, expressing them in kre1Δ S. cerevisiae, and observing their levels of sensitivity to K1. I expect to find that successful expression of KRE1 in kre1Δ S. cerevisiae cells will result in sensitivity to K1. Understanding the susceptibility determinants of pathogenic fungi will enable the potential future application of K1 as a novel therapeutic.
The Cell Membrane Protein Kre1 as a Receptor for the K1 Killer Toxin in Pathogenic Yeasts
Killer yeasts are single-celled members of the Fungal kingdom that have the ability to create antifungal proteins called killer toxins. These killer toxins compete with other yeasts in their environment to inhibit growth and kill fungal cells. Due to these functions, killer yeasts are studied for their biomedical potential. Statistically speaking,1 in 3 women will get a yeast infection at one point in their lives. To treat vaginal yeast infections, azoles are the most commonly prescribed class of drugs, and are thought to be as much as 32% ineffective for treating these infections. Candida glabrata is a yeast responsible for vulvovaginal candidiasis and is highly susceptible to a killer toxin named K1, produced by baker’s yeast (Saccharomyces cerevisiae). Kre1 is believed to be the secondary cell receptor for K1, potentially playing a role in yeast cell sensitivity. I hypothesize that Kre1 is the primary determinant of K1 sensitivity in diverse Ascomycota yeasts. This hypothesis is supported by findings from Breinig et al., among others, as their research found kre1Δ cells are completely resistant to K1, and expression of KRE1 restored sensitivity. I will be further testing this hypothesis by extracting, cloning, and modifying KRE1s from a variety of Candida yeasts, expressing them in kre1Δ S. cerevisiae, and observing their levels of sensitivity to K1. I expect to find that successful expression of KRE1 in kre1Δ S. cerevisiae cells will result in sensitivity to K1. Understanding the susceptibility determinants of pathogenic fungi will enable the potential future application of K1 as a novel therapeutic.