Genome-wide gene expression tuning reveals diverse vulnerabilities of M. tuberculosis.

ABSTRACT: Antibacterial agents target the products of essential genes but rarely achieve complete target inhibition. Thus, the all-or-none definition of essentiality afforded by traditional genetic approaches fails to discern the most attractive bacterial targets: those whose incomplete inhibition results in major fitness costs. In contrast, gene "vulnerability" is a continuous, quantifiable trait that relates the magnitude of gene inhibition to the effect on bacterial fitness. We developed a CRISPR interference-based functional genomics method to systematically titrate gene expression in Mycobacterium tuberculosis (Mtb) and monitor fitness outcomes. We identified highly vulnerable genes in various processes, including novel targets unexplored for drug discovery. Equally important, we identified inv

SUBMITTER: Bosch B 

PROVIDER: S-EPMC8382161 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature