Divergent transcriptional regulation of redox-homeostasis and permeability modulate rifampicin tolerance and sensitivity in Mycobacterium tuberculosis.

ABSTRACT: Drug-tolerance in Mycobacterium tuberculosis (Mtb) may delay treatment response while drug hypersusceptibility should improve treatment. We investigate the transcriptional regulation of these states in Mtb using a Transcriptional Regulator Induced Phenotype screen combined with an extended, steady-state rifampicin exposure method. We identify three transcription factors (TFs): Rv1359, Rv2887, and Rv3833, whose induction enhances rifampicin tolerance, and four TFs, Rv1189 (sigI), Rv1846c (blaI), Rv2069 (sigC), and Rv3736, whose induction elicits hypersusceptibility. Inducing the TFs blaI and Rv2887 produces opposite phenotypes due to their divergent regulation of the cydA and icl1, genes that we find to reduce redox stress when overexpressed. Thus, Rv2887 induces icl1 expression which contr

SUBMITTER: Sebastian J 

PROVIDER: S-EPMC12800208 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature