1H-Benzo[d]Imidazole Derivatives Affect MmpL3 in Mycobacterium tuberculosis.

ABSTRACT: 1H-benzo[d]imidazole derivatives exhibit antitubercular activity in vitro at a nanomolar range of concentrations and are not toxic to human cells, but their mode of action remains unknown. Here, we showed that these compounds are active against intracellular Mycobacterium tuberculosis To identify their target, we selected drug-resistant M. tuberculosis mutants and then used whole-genome sequencing to unravel mutations in the essential mmpL3 gene, which encodes the integral membrane protein that catalyzes the export of trehalose monomycolate, a precursor of the mycobacterial outer membrane component trehalose dimycolate (TDM), as well as mycolic acids bound to arabinogalactan. The drug-resistant phenotype was also observed in the parental strain ove

SUBMITTER: Korycka-Machala M 

PROVIDER: S-EPMC6761528 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature