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However, despite the potency of HOCl, some ingested Staphylococcus aureus cells survive within PMNs and contribute to disease. To identify factors that support the resistance of ingested staphylococci to PMN-oxidative killing, we screened the Nebraska Transposon Mutant Library in the USA300 methicillin-resistant S. aureus strain for mutants that were more sensitive or resistant to HOCl. We identified a mutant in mazF that survived challenge with reagent HOCl better than did the parental strain. In addition, the mutant resisted killing by human PMNs, suggesting that MazF contributes to the susceptibility of S. aureus to HOCl-mediated damage, the ability of S. aureus to recover from HOCl attack, or both. To confirm the genetic basis of the MazF phenotypes, we transformed the mutant with an expression plasmid carrying the wild-type mazF gene or the empty vector control to complement the phenotype. The deletion mutant with the empty vector survived better in reagent HOCl and in PMNs than did the parental strain or the complemented deletion mutant. Taken together, these data suggest that in the absence of mazF expression, USA300 methicillin-resistant S. aureus better resisted, repaired, or both resisted and repaired the sublethal damage produced by HOCl alone or by antimicrobial elements in human PMNs.<\/jats:p>","DOI":"10.1093\/jleuko\/qiaf057","type":"journal-article","created":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T13:17:50Z","timestamp":1747660670000},"source":"Crossref","is-referenced-by-count":3,"title":["Mutation in <i>Staphylococcus aureus<\/i> that supports gain of function in susceptibility both to hypochlorous acid and to human neutrophils"],"prefix":"10.1093","volume":"117","author":[{"given":"Athmane","family":"Teghanemt","sequence":"first","affiliation":[{"name":"Inflammation Program and Department of Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa , 523 Eckstein Medical Research Building, 431 Newton Road, Iowa City, IA 52242 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"Schilcher","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, School of Medicine, University of Colorado Anschutz Medical Campus , 12800 East 19th Avenue\/Mail Stop 8333, Aurora, CO 80045 ,","place":["United States"]},{"name":"Department of Genetics, Genomics and Cancer Sciences, University of Leicester , Adrian Building, University Road, Leicester LE1 7RH ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffery S","family":"Kavanaugh","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, School of Medicine, University of Colorado Anschutz Medical Campus , 12800 East 19th Avenue\/Mail Stop 8333, Aurora, CO 80045 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander R","family":"Horswill","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, School of Medicine, University of Colorado Anschutz Medical Campus , 12800 East 19th Avenue\/Mail Stop 8333, Aurora, CO 80045 ,","place":["United States"]},{"name":"Department of Veterans Affairs Eastern Colorado Health Care System , 1700 N Wheeling St., Aurora, CO 80045 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4032-757X","authenticated-orcid":false,"given":"William M","family":"Nauseef","sequence":"additional","affiliation":[{"name":"Inflammation Program and Department of Medicine, Roy J. and Lucille A. 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