{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T22:50:34Z","timestamp":1773787834735,"version":"3.50.1"},"reference-count":55,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,12,25]],"date-time":"2025-12-25T00:00:00Z","timestamp":1766620800000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["mLife"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    is a notorious opportunistic pathogen with remarkable adaptability, enabling it to infect virtually every human tissue. Staphyloxanthin (STX), a critical virulence factor, contributes to\n                    <jats:italic>S. aureus<\/jats:italic>\n                    oxidative damage. However, the regulatory mechanism of STX production is incompletely understood. This study provides mechanistic insights into the role of catabolite control protein A (CcpA) in STX production.\n                    <jats:italic>ccpA<\/jats:italic>\n                    deletion considerably reduced STX yield in\n                    <jats:italic>S. aureus<\/jats:italic>\n                    strains with diverse genetic lineages. Western blot showed that CcpA inactivation did not alter SigB expression levels in\n                    <jats:italic>S. aureus<\/jats:italic>\n                    . Gene reporter and electrophoretic mobility shift assays revealed the direct control of CcpA on the expression of the\n                    <jats:italic>crtOPQMN<\/jats:italic>\n                    operon, which encodes enzymes for step\u2010wise STX biosynthesis. Moreover, CcpA deficiency remarkably impaired bacterial tolerance to H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    \u2010mediated killing, decreased survival in whole\u2010blood treatment, and diminished persistence in macrophages. In mouse bacteremia and skin abscess models, CcpA was shown to enhance\n                    <jats:italic>S. aureus<\/jats:italic>\n                    virulence. Notably, inhibition of CcpA with Ag\n                    <jats:sup>+<\/jats:sup>\n                    synergized with vancomycin to combat vancomycin\u2010intermediate\n                    <jats:italic>S. aureus<\/jats:italic>\n                    infections in vivo. Our findings establish CcpA as a SigB\u2010independent regulator of STX production, suggesting that targeting CcpA could be a promising antibiotic synergistic strategy for the management of multidrug\u2010resistant\n                    <jats:italic>S. aureus<\/jats:italic>\n                    infections.\n                  <\/jats:p>","DOI":"10.1002\/mlf2.70040","type":"journal-article","created":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T07:15:53Z","timestamp":1766733353000},"page":"651-663","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["CcpA promotes\n                    <i>Staphylococcus aureus<\/i>\n                    virulence by directly controlling staphyloxanthin production"],"prefix":"10.1002","volume":"4","author":[{"given":"Xian","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine Xinqiao Hospital, Army Medical University Chongqing 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