Premium
Mycobacterium tuberculosis expresses methionine sulphoxide reductases A and B that protect from killing by nitrite and hypochlorite
Author(s) -
Lee Warren L.,
Gold Benjamin,
Darby Crystal,
Brot Nathan,
Jiang Xiuju,
De Carvalho Luiz Pedro S.,
Wellner Daniel,
St. John Gregory,
Jacobs Jr William R.,
Nathan Carl
Publication year - 2009
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.2008.06548.x
Subject(s) - msra , methionine , biology , mutant , biochemistry , mycobacterium tuberculosis , wild type , microbiology and biotechnology , escherichia coli , tuberculosis , amino acid , medicine , pathology , gene
Summary 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 Δ msrA‐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.