Neutrophils generate HOCl, a bactericidal oxidant, through the enzymatic activity of myeloperoxidase. HOCl oxidizes methionine residues to methionine sulfoxide. (A) Repair of methionine sulfoxide by the methionine sulfoxide reductases (Msr) is critical for the survival of S. aureus. USA300 wildtype and Δmsr were treated with and with out HOCl. Growth was monitored by optical density at 600 nm. While HOCl attenuates the growth of both strains, no growth of the the Δmsr strain is visible 24 h following HOCl treatment. (B) To determine if the phenotype observed in panel A is bacteriostatic or bactericidal, USA300 wildtype and Δmsr were treated with multiple concentrations of HOCl. After incubation, the samples were dilution plated on solid medium to enumerate viable bacteria. HOCl kills more than 1000-fold more bacteria of the Δmsr strain compared to USA300 wildtype. In total, these data demonstrate the critical role of the Msr enzymes in protecting S. aureus from oxidative killing.