Compensatory evolution in NusG improves fitness of drug-resistant M. tuberculosis.

ABSTRACT: Drug-resistant bacteria are emerging as a global threat, despite frequently being less fit than their drug-susceptible ancestors^1-8. Here we sought to define the mechanisms that drive or buffer the fitness cost of rifampicin resistance (RifR) in the bacterial pathogen Mycobacterium tuberculosis (Mtb). Rifampicin inhibits RNA polymerase (RNAP) and is a cornerstone of modern short-course tuberculosis therapy^9,10. However, RifR Mtb accounts for one-quarter of all deaths due to drug-resistant bacteria^11,12. We took a comparative functional genomics approach to define processes that are differentially vulnerable to CRISPR interference (CRISPRi) inhibition in RifR Mtb. Among other hits, we found that the universally conserved transcription factor NusG is crucial

SUBMITTER: Eckartt KA 

PROVIDER: S-EPMC10990936 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature