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By leveraging a rodent-adapted strain of\n            <jats:italic>S. aureus<\/jats:italic>\n            , we developed a natural model of SSTIs. We found that LukMF\u2032, a pore-forming leukocidin homolog to the human-specific LukSF-PV toxin, drives skin pathology in mice. LukMF\u2032 lyses neutrophils via the chemokine receptor CCR1, which in turn fuels inflammatory pathology and microbial survival within the infectious nidus. Ablation of CCR1, depletion of neutrophils, or vaccination with LukMF\u2032 all protected mice from skin pathology. Thus, these data support epidemiological studies linking leukocidins with human SSTIs and highlight the power of natural models to unearth potential targets to curtail infections.\n          <\/jats:p>","DOI":"10.1126\/sciadv.adr5240","type":"journal-article","created":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T17:58:27Z","timestamp":1751651907000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":7,"title":["<i>Staphylococcus aureus<\/i>\n            LukMF\u2032 targets neutrophils to promote skin and soft tissue infection"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8127-916X","authenticated-orcid":true,"given":"Daiane","family":"Boff","sequence":"first","affiliation":[{"name":"Department of Microbiology, New York University Grossman School of Medicine, New York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravishankar","family":"Chandrasekaran","sequence":"additional","affiliation":[{"name":"Department of Host-Microbe Interactions, St. Jude Children\u2019s Research Hospital, Memphis, TN, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Putzel","sequence":"additional","affiliation":[{"name":"Microbial Computational Genomic Core Lab, Antimicrobial-Resistant Pathogens Program, New York University Grossman School of Medicine, New York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3927-2508","authenticated-orcid":true,"given":"Rachel M.","family":"Kratofil","sequence":"additional","affiliation":[{"name":"Department of Immunology and Immunotherapy &amp; Department of Dermatology, Icahn School of Medicine at Mt. 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