Methionine sulfoxide reductases protect against oxidative stress in Staphylococcus aureus encountering exogenous oxidants and human neutrophils.

Methionine sulfoxide reductases protect against oxidative stress in Staphylococcus aureus encountering exogenous oxidants and human neutrophils.
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DOI:
10.1159/000355915
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发表时间:
2014
影响因子:
5.3
通讯作者:
Nauseef WM
Nauseef WM
中科院分区:
医学2区
文献类型:
--
作者:
Pang YY;Schwartz J;Bloomberg S;Boyd JM;Horswill AR;Nauseef WM

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To establish infection successfully, S. aureus must evade clearance by polymorphonuclear neutrophils (PMN). We studied the expression and regulation of the methionine sulfoxide reductases (Msr) that are involved in the repair of oxidized staphylococcal proteins and investigated their influence over the fate of S. aureus exposed to oxidants or PMN. We evaluated a mutant deficient in msrA1 and msrB for susceptibility to hydrogen peroxide, hypochlorous acid and PMN. The expression of msrA1 in wild-type bacteria ingested by human PMN was assessed by real-time PCR. The regulation of msr was studied by screening a library of two-component regulatory system (TCS) mutants for altered msr responses. Relative to the wild-type, bacteria deficient in Msr were more susceptible to oxidants and to PMN. Upregulation of staphylococcal msrA1 occurred within the phagosomes of normal PMN and PMN deficient in NADPH oxidase activity. Furthermore, PMN granule-rich extract stimulated the upregulation of msrA1. Modulation of msrA1 within PMN was shown to be partly dependent on the VraSR TCS. Msr contributes to staphylococcal responses to oxidative attack and PMN. Our study highlights a novel interaction between the oxidative protein repair pathway and the VraSR TCS that is involved in cell wall homeostasis.
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