{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T17:25:26Z","timestamp":1787160326211,"version":"build-2736575974"},"posted":{"date-parts":[[2025,12,14]]},"group-title":"Microbiology","reference-count":61,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T00:00:00Z","timestamp":1765670400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["R01 EY14362"],"award-info":[{"award-number":["R01 EY14362"]}],"id":[{"id":"https:\/\/ror.org\/03wkg3b53","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,12,14]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  <jats:italic>Staphylococcus aureus<\/jats:italic>\n                  \u03b1-hemolysin (Hla) is a major virulence factor that utilizes cell surface ADAM10 to oligomerize and form a functional heptameric pore. We show here that Hla from strain USA300 is required to induce IL-1\u03b2 secretion by neutrophils and to cause severe corneal disease in mice. We also demonstrate that in contrast to USA300 and other clonal complex 8 (CC8) methicillin resistant\n                  <jats:italic>S. aureus<\/jats:italic>\n                  (MRSA) isolated from the skin, CC5 Hla from corneas of infected patients have single nucleotide polymorphisms (SNP) that result in two amino acid substitutions, D208E (Asp-Glu) and I275T (Ile-Thr). Structural modeling predicts CC5 Hla self-assembly and altered binding to ADAM10 that is distinct from CC8 Hla. The ADAM10 inhibitor GI254023X blocked neutrophil IL-1\u03b2 secretion induced by Hla-expressing CC8, but not by CC5 conditioned media, indicating that these Hla polymorphisms play an important role in Hla receptor binding and neutrophil IL-1\u03b2 secretion, and affect corneal disease severity.\n                <\/jats:p>","DOI":"10.64898\/2025.12.13.694139","type":"posted-content","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T02:20:12Z","timestamp":1765765212000},"source":"Crossref","is-referenced-by-count":2,"title":["\u03b1-hemolysin polymorphisms in methicillin-resistant\n                  <i>Staphylococcus aureus<\/i>\n                  clinical isolates regulate ADAM10-dependent neutrophil IL-1\u03b2 secretion"],"prefix":"10.64898","author":[{"given":"Karl","family":"Liboro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jolynn T.","family":"Chau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James D.","family":"Begando","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Abbondante","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Lackner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela E.","family":"Marshall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nghi","family":"Ly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor D.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George R.","family":"Dubyak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Gilmore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reginald","family":"McNulty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Andre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0137-7582","authenticated-orcid":false,"given":"Eric","family":"Pearlman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025121704401062000_2025.12.13.694139v1.1","first-page":"1946","article-title":"Antimicrobial Resistance: A Growing Serious Threat for Global Public Health","volume":"11","year":"2023","journal-title":"Healthcare (Basel"},{"key":"2025121704401062000_2025.12.13.694139v1.2","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens10101310"},{"key":"2025121704401062000_2025.12.13.694139v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-024-01054-w"},{"key":"2025121704401062000_2025.12.13.694139v1.4","doi-asserted-by":"publisher","DOI":"10.3201\/eid2111.150452"},{"key":"2025121704401062000_2025.12.13.694139v1.5","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-144-5-200603070-00005"},{"key":"2025121704401062000_2025.12.13.694139v1.6","doi-asserted-by":"publisher","DOI":"10.1086\/499815"},{"key":"2025121704401062000_2025.12.13.694139v1.7","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1038\/s41433-020-01339-3","article-title":"Infectious keratitis: an update on epidemiology, causative microorganisms, risk factors, and antimicrobial resistance","volume":"35","year":"2021","journal-title":"Eye (Lond"},{"key":"2025121704401062000_2025.12.13.694139v1.8","doi-asserted-by":"crossref","unstructured":"Shah, S. & Wozniak, R. 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