Mycobacterium tuberculosis metC (Rv3340) derived hydrogen sulphide conferring bacteria stress survival

J Drug Target. 2019 Nov;27(9):1004-1016. doi: 10.1080/1061186X.2019.1579820. Epub 2019 Mar 21.

Abstract

Tuberculosis, especially multidrug resistant cases, remains an enormous public health threat. Mycobacterium tuberculosis metC (Rv3340) an enzyme involved in methionine biosynthesis was identified and characterised for antimicrobial susceptibility. We reported that the overexpression of Rv3340 in Mycobacterium smegmatis (Ms_Rv3340) produces hydrogen sulphide (H2S) for its energy in harsh conditions. The produced H2S sustained Ms_Rv3340 against streptomycin, whereas the chemical inhibition of H2S caused streptomycin lethality to Ms_Rv3340. Further analysis showed that cysteine-H2O2 treatment of Ms-Rv3340 initiated DNA damage via Fenton reaction. Ms_Rv3340 downregulated the expression levels of three streptomycin responsive genes. To our knowledge, no study has been previously reported that M. tuberculosis metC (Rv3340) can generates H2S modulating resistant to streptomycin which provides a greater perception toward the treatment and control of tuberculosis.

Keywords: Mycobacterium tuberculosis Rv3340; hydrogen sulphide; metC; methionine; streptomycin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitubercular Agents / pharmacology*
  • Cysteine / administration & dosage
  • DNA Damage / drug effects
  • Gene Expression Regulation, Bacterial
  • Genes, Bacterial / drug effects
  • Hydrogen Peroxide / administration & dosage
  • Hydrogen Sulfide / metabolism
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / enzymology
  • Streptomycin / pharmacology*
  • Tuberculosis, Multidrug-Resistant / drug therapy*
  • Tuberculosis, Multidrug-Resistant / enzymology

Substances

  • Antitubercular Agents
  • Hydrogen Peroxide
  • Cysteine
  • Streptomycin
  • Hydrogen Sulfide