Mechanistic and Structural Insights Into the Unique TetR-Dependent Regulation of a Drug Efflux Pump in Mycobacterium abscessus.

ABSTRACT: Mycobacterium abscessus is an emerging human pathogen causing severe pulmonary infections and is refractory to standard antibiotherapy, yet few drug resistance mechanisms have been reported in this organism. Recently, mutations in MAB_4384 leading to up-regulation of the MmpS5/MmpL5 efflux pump were linked to increased resistance to thiacetazone derivatives. Herein, the DNA-binding activity of MAB_4384 was investigated by electrophoretic mobility shift assays using the palindromic sequence IR_S5/L5 located upstream of mmpS5/mmpL5. Introduction of point mutations within IR_S5/L5 identified the sequence requirements for optimal binding of the regulator. Moreover, formation of the protein/IR_S5/L5 complex was severely impaired for MAB_4384 ha

SUBMITTER: Richard M 

PROVIDER: S-EPMC5895659 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature