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

Yun Yun Pang, Jamie Schwartz, Sarah Bloomberg, Jeffrey M. Boyd, Alexander R. Horswill, William M. Nauseef

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

To establish infection successfully, Staphylococcus 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 on 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, bacteria deficient in Msr were more susceptible to oxidants and 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.

Original languageEnglish (US)
Pages (from-to)353-364
Number of pages12
JournalJournal of Innate Immunity
Volume6
Issue number3
DOIs
StatePublished - Mar 2014

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy

Keywords

  • Methionine sulfoxide reductase
  • Neutrophils
  • Oxidative stress
  • Staphylococcus aureus

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