Targeting redox heterogeneity to counteract drug tolerance in replicating <i>Mycobacterium tuberculosis</i>.

ABSTRACT: The capacity of Mycobacterium tuberculosis (Mtb) to tolerate multiple antibiotics represents a major problem in tuberculosis (TB) management. Heterogeneity in Mtb populations is one of the factors that drives antibiotic tolerance during infection. However, the mechanisms underpinning this variation in bacterial population remain poorly understood. Here, we show that phagosomal acidification alters the redox physiology of Mtb to generate a population of replicating bacteria that display drug tolerance during infection. RNA sequencing of this redox-altered population revealed the involvement of iron-sulfur (Fe-S) cluster biogenesis, hydrogen sulfide (H₂S) gas, and drug efflux pumps in antibiotic tolerance. The fraction of the pH- and redox-dependent tol

SUBMITTER: Mishra R 

PROVIDER: S-EPMC7212044 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature