Multidrug tolerance conferred by loss-of-function mutations in anti-sigma factor RshA of Mycobacterium abscessus.

ABSTRACT: Low-level drug resistance in noncanonical pathways can constitute steppingstones toward acquisition of high-level on-target resistance mutations in the clinic. To capture these intermediate steps in Mycobacterium abscessus (Mab), we performed classic mutant selection experiments with moxifloxacin at twofold its minimum inhibitory concentration (MIC) on solid medium. We found that low-level resistance emerged reproducibly as loss-of-function mutations in RshA (MAB_3542c), an anti-sigma factor that negatively regulates activity of SigH, which orchestrates a response to oxidative stress in mycobacteria. Since oxidative stress is generated in response to many antibiotics, we went on to show that deletion of rshA confers low to moderate resistance-by measure of MIC-to a dozen agen

SUBMITTER: Aragaw WW 

PROVIDER: S-EPMC11619451 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature