Mycobacterium tuberculosis expresses methionine sulphoxide reductases A and B that protect from killing by nitrite and hypochlorite

Warren L. Lee, Benjamin Gold, Crystal Darby, Nathan Brot, Xiuju Jiang, Luiz Pedro S. De Carvalho, Daniel Wellner, Gregory St. John, William R. Jacobs, Carl Nathan

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

Methionine sulphoxide reductases (Msr) reduce methionine sulphoxide to methionine and protect bacteria against reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI). Many organisms express both MsrA, active against methionine-(S)-sulphoxide, and MsrB, active against methionine-(R)- sulphoxide. Mycobacterium tuberculosis (Mtb) expresses MsrA, which protects ΔmsrA-Escherichia coli from ROI and RNI. However, the function of MsrA in Mtb has not been defined, and it is unknown whether Mtb expresses MsrB. We identified MsrB as the protein encoded by Rv2674 in Mtb and confirmed the distinct stereospecificities of recombinant Mtb MsrA and MsrB. We generated strains of Mtb deficient in MsrA, MsrB or both and complemented the mutants. Lysates of singly deficient strains displayed half as much Msr activity as wild type against N-acetyl methionine sulphoxide. However, in contrast to other bacteria, single mutants were no more vulnerable than wild type to killing by ROI/RNI. Only Mtb lacking both MsrA and MsrB was more readily killed by nitrite or hypochlorite. Thus, MsrA and MsrB contribute to the enzymatic defences of Mtb against ROI and RNI.

Original languageEnglish (US)
Pages (from-to)583-593
Number of pages11
JournalMolecular Microbiology
Volume71
Issue number3
DOIs
StatePublished - Feb 2009

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

Fingerprint

Dive into the research topics of 'Mycobacterium tuberculosis expresses methionine sulphoxide reductases A and B that protect from killing by nitrite and hypochlorite'. Together they form a unique fingerprint.

Cite this