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This study evaluated the therapeutic potential of Schisandrin C (Sch C), a natural lignan derived from\n                      <jats:italic toggle=\"yes\">Schisandra chinensis<\/jats:italic>\n                      , in mitigating MRSA-induced OM. In rat models of MRSA-induced AOM and CSOM, Sch C significantly reduced bacterial load and inflammatory responses by decreasing pro-inflammatory cytokine levels. By upregulating tight junction protein ZO-1 and downregulating mucin MUC5B, it also restored epithelial barrier integrity. In addition, Sch C treatment improved auditory function. Mechanistic studies revealed that Sch C directly inhibited sortase A (SrtA), a key enzyme responsible for anchoring surface virulence factors in MRSA, by binding to its active site and inhibiting its transpeptidase activity (fluorescence resonance energy transfer IC\u2085\u2080 = 38.68 \u00b5M). Through inhibiting SrtA, Sch C disrupted MRSA adhesion, invasion, and biofilm formation without exerting direct bactericidal effects. Furthermore, Sch C synergized with ofloxacin, enhancing its efficacy against MRSA otitis by reducing bacterial load, inflammation, and tissue damage. Collectively, these findings establish Sch C as a potent\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      SrtA inhibitor, highlighting its promise as a therapeutic strategy for MRSA-induced OM.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00095-26","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T14:29:14Z","timestamp":1781101754000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["The protective effect of Schisandrin C against methicillin-resistant\n                    <i>Staphylococcus aureus<\/i>\n                    -induced otitis 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