Genetic Screens of an Anti-Candida Natural Product Using the Heterozygous Saccharomyces cerevisiae Mutant Library

Candida albicans is one of the most common fungal pathogens in humans. Due to the development of resistance to antifungal drugs, today there is a need for finding new antifungal agents with new pharmacological targets for a more efficient management of C. albicans infections. Drug repositioning or drug repurposing has been exploited to develop new antifungal approaches. Natural products may be more easily developed because they have been a useful source of active antimicrobials. Additionally, new antifungals are needed to combat drug-resistant infections caused by fungi such as by Candida species. Once compounds are identified, determining the mode of action (MOA) of natural products is a key objective. Genetic screens utilizing the Saccharomyces cerevisiae heterozygous mutant library provides a direct link between a phenotypic screen (easy read-out) and the identity of the gene target. Screens using mutant libraries can identify chemical-genetic interactions and genes or pathways affected by compounds to decipher the mechanism of action. Herein, we describe a genetic screen of an anti-Candida natural product.