Mycobacterium tuberculosis Rv0191 is an efflux pump of major facilitator superfamily transporter regulated by Rv1353c

Arch Biochem Biophys. 2019 May 30:667:59-66. doi: 10.1016/j.abb.2019.04.010. Epub 2019 May 1.

Abstract

Development of extensively drug resistant (XDR) strains and multidrug resistant (MDR) in Mycobacterium tuberculosis is caused by an efflux mechanism of antibiotics in the bacteria. Rv0191, predicted to a major facilitator superfamily transporter of efflux pump, contributes to elevated expression in some clinical isolates. To characterize the role of Rv0191 which might be involved in antibiotics resistance, Mycobacterium smegmatis was taken as a type strains to do drug susceptibility, ethidium bromide (EB) accumulation assay and electrophoretic mobility shift assay. M. smegmatis Ms0232 mutant became more susceptible to chloramphenicol and showed different cell surface properties. Rv1353c, a TetR family transcription factor, can downregulate the transcription of Rv0191. Rv1353c overexpression strain became more sensitive to chloramphenicol. Together, these findings indicate that Rv1353c encodes a transcriptional repressor that directly interacts with the Rv0191 promoter and modulates the expression of Rv0191. This provided a new player in mycobacteria chloramphenicol resistance.

Keywords: Chloramphenicol; Efflux pump; Major facilitator superfamily; Mycobacterium tuberculosis; Rv0191.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Chloramphenicol / pharmacokinetics
  • Chloramphenicol / pharmacology
  • Drug Resistance, Bacterial / genetics
  • Gene Expression Regulation, Bacterial
  • Gene Knockout Techniques
  • Genes, Bacterial
  • Humans
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism*
  • Mycobacterium smegmatis / drug effects
  • Mycobacterium smegmatis / genetics
  • Mycobacterium smegmatis / metabolism
  • Mycobacterium tuberculosis / drug effects
  • Mycobacterium tuberculosis / genetics
  • Mycobacterium tuberculosis / metabolism*
  • Promoter Regions, Genetic

Substances

  • Bacterial Proteins
  • Membrane Transport Proteins
  • Chloramphenicol