Attenuating the emergence of anti-fungal drug resistance by harnessing synthetic lethal interactions in a model organism.

ABSTRACT: Drug resistance is a rapidly emerging concern, thus prompting the development of novel therapeutics or combinatorial therapy. Currently, combinatorial therapy targets are based on knowledge of drug mode of action and/or resistance mechanisms, constraining the number of target proteins. Unbiased genome-wide screens could reveal novel genetic components within interaction networks as potential targets in combination therapies. Testing this, in the context of antimicrobial resistance, we implemented an unbiased genome-wide screen, performed in Saccharomyces cerevisiae expressing a Candida glabrata PDR1+ gain-of-function allele. Gain-of-function mutations in this gene are the principal mediators of fluconazole resistance in this human fungal pathogen. Eighteen synthetically lethal S. cerevisia

SUBMITTER: Usher J 

PROVIDER: S-EPMC6715234 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature