{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T13:50:57Z","timestamp":1781790657751,"version":"3.54.5"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Shanghai Pujiang Talents Program","award":["24PJD094"],"award-info":[{"award-number":["24PJD094"]}]},{"name":"2024 Academic Year Discipline Construction Funding - Development Discipline - Laboratory Department","award":["202509-5576"],"award-info":[{"award-number":["202509-5576"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This study aimed to investigate the anti-virulence effects of subinhibitory concentration of clarithromycin on Staphylococcus aureus and to explore the underlying molecular mechanism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Haemolytic activity was measured using rabbit erythrocytes. \u03b1-haemolysin production was assessed by Western blot analysis. Transcriptional changes were analysed by RT\u2013qPCR and promoter activity assays. To verify the target mechanism, a \u0394saeR mutant and a complemented strain were constructed. Molecular docking and DARTS assay were employed to evaluate the potential clarithromycin\u2013SaeR interaction. Substitution of a single residue, Arg154, with alanine was performed to determine its functional role. In vivo efficacy of clarithromycin was assessed using the Galleria mellonella infection model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Clarithromycin at 1\/8MIC reduced haemolytic activity in methicillin-resistant S. aureus strains MR200 and MR271 from 83.61%\u200a\u00b1\u200a0.86% to 9.05%\u200a\u00b1\u200a4.13% and from 85.12%\u200a\u00b1\u200a1.95% to 45.24%\u200a\u00b1\u200a1.06%, respectively, and significantly decreased \u03b1-haemolysin production. Clarithromycin selectively downregulated saeR, with a 1.87-fold reduction in MR200 and 1.54-fold reduction in MR271, while the agr pathway remained largely unaffected. Promoter activity assays confirmed suppression of the saeR-P1 promoter. Haemolytic activity and \u03b1-haemolysin production were significantly reduced in the \u0394saeR mutant, and clarithromycin caused no additional inhibition, and these effects were restored upon saeR complementation. Molecular docking and DARTS assay suggested a potential SaeR-clarithromycin binding. Arg154 substitution eliminated both SaeR regulatory activity and drug-mediated virulence suppression. In vivo, 1\/8MIC clarithromycin improved larval survival to over 90%.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study demonstrated that clarithromycin exerted an anti-virulence effect against S. aureus by targeting the SaeR, highlighting a potential strategy for repurposing antibiotics to mitigate bacterial pathogenicity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkag220","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T11:51:42Z","timestamp":1781092302000},"source":"Crossref","is-referenced-by-count":0,"title":["Subinhibitory concentration of clarithromycin targets SaeR to reduce the haemolytic activity of\n                    <i>Staphylococcus aureus<\/i>"],"prefix":"10.1093","volume":"81","author":[{"given":"Xinru","family":"Yuan","sequence":"first","affiliation":[{"name":"Department of Clinical 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