Methionine sulfoxide reductases and virulence of bacterial pathogens

Abstract

Oxidation of methionine (Met) residues in proteins by reactive oxygen species and reactive nitrogen intermediates results in altered protein structures, which subsequently affect their functions. Oxidized Met (Met-O) residues are reduced to Met by the methionine sulfoxide reductase (Msr) system, which includes mainly MsrA and MsrB. MsrA and MsrB show no sequence and structural identity with each other but both reduce methionine sulfoxides. MsrA is specific to the reduction of methionine-S-sulfoxide, whereas MsrB is specific to the reduction of methionine-R-sulfoxide. Genes encoding the enzymes MsrA and MsrB exist in most living organisms including bacteria. In recent times, absence of these enzymes has been implicated in the virulence of bacterial pathogens. In particular, pathogens deficient in Msr have been reported to have reduced ability to adhere with eukaryotic cells, to survive inside hosts and to resist in vitro oxidative stress. Bacterial proteins that are susceptible to Met oxidation, in the absence of Msr, have also been identified. This review discusses the current knowledge on the role of Msr in bacterial virulence.