Abstract Title

The Discovery of Novel Aerolysin Homologs within Yeasts

Additional Funding Sources

The project described was supported by the Research Experience for Undergraduates Program Site: Molecular and organismal evolution at the University of Idaho under Award No. 1757826 and a student grant from the UI Office of Undergraduate Research.

Abstract

Aerolysin toxins are a class of Β-Pore Forming Toxins that, while mainly described as a virulence factor for bacterial pathogens, have been found in fungal organisms and exhibit extreme toxicity towards human cells. Various fungi from the Saccharomycetaceae family produce antifungal “Killer” toxins that benefit the host in many ways such as reducing the competitive growth or providing another mechanism for nutrient acquisition. Structural modeling of a “K62” killer toxin produced by Saccharomyces yeasts, commonly used for processes involving fermentation, shows homology to aerolysin toxins. To better understand how the toxin may be used in situ, a search for K62 homologs was performed and 123 were identified within numerous plant and animal pathogenic organisms; most notably the opportunistic fungal pathogen Candida glabrata. As determined by ectopic expression, these homologs do indeed encode for a functional killer toxin in addition to altering the hosts sensitivity to the K62 toxin as compared to the wild type. Currently, we are determining at what temperature and pH the K62 toxin exhibits optimal killing activity. We aim to learn what contribution these toxins have towards fungal virulence and to explore their potential as a novel treatment for other fungal infections.

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The Discovery of Novel Aerolysin Homologs within Yeasts

Aerolysin toxins are a class of Β-Pore Forming Toxins that, while mainly described as a virulence factor for bacterial pathogens, have been found in fungal organisms and exhibit extreme toxicity towards human cells. Various fungi from the Saccharomycetaceae family produce antifungal “Killer” toxins that benefit the host in many ways such as reducing the competitive growth or providing another mechanism for nutrient acquisition. Structural modeling of a “K62” killer toxin produced by Saccharomyces yeasts, commonly used for processes involving fermentation, shows homology to aerolysin toxins. To better understand how the toxin may be used in situ, a search for K62 homologs was performed and 123 were identified within numerous plant and animal pathogenic organisms; most notably the opportunistic fungal pathogen Candida glabrata. As determined by ectopic expression, these homologs do indeed encode for a functional killer toxin in addition to altering the hosts sensitivity to the K62 toxin as compared to the wild type. Currently, we are determining at what temperature and pH the K62 toxin exhibits optimal killing activity. We aim to learn what contribution these toxins have towards fungal virulence and to explore their potential as a novel treatment for other fungal infections.