Abstract
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.