EthA/R-Independent Killing of Mycobacterium tuberculosis by Ethionamide.

ABSTRACT: Ethionamide (ETH) is part of the drug arsenal available to treat multi-drug resistant tuberculosis. The current paradigm of this pro-drug activation involves the mycobacterial enzyme EthA and the transcriptional repressor, EthR. However, several lines of evidence suggest the involvement of additional players. The ethA/R locus was deleted in Mycobacterium bovis BCG and three Mycobacterium tuberculosis (MTB) strains. While complete resistance to ETH was observed with BCG ethA/R KO, drug susceptibility and dose-dependent killing were retained in the ethA/R KO MTB mutants, suggesting the existence of an alternative pathway of ETH bio-activation in MTB. We further demonstrated that this alternative pathway is EthR-independent, whereby re-introduction of eth

SUBMITTER: Ang MLT 

PROVIDER: S-EPMC5403819 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature