{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T11:47:15Z","timestamp":1780573635752,"version":"3.54.1"},"reference-count":44,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T00:00:00Z","timestamp":1719273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T00:00:00Z","timestamp":1719273600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82260085"],"award-info":[{"award-number":["82260085"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The science and technology program of Jangxi traditional chinese medicine","award":["2021B723"],"award-info":[{"award-number":["2021B723"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mSphere"],"published-print":{"date-parts":[[2024,6,25]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              The emerging prevalence of drug-resistant\n              <jats:italic>Staphylococcus aureus<\/jats:italic>\n              isolates underscores the urgent need for alternative therapeutic strategies due to the declining effectiveness of traditional antibiotics in clinical settings. MgrA, a key virulence regulator in\n              <jats:italic>S. aureus<\/jats:italic>\n              , orchestrates the expression of numerous virulence factors. Here, we report the discovery of isorhapontigenin, a methoxylated analog of resveratrol, as a potential anti-virulence agent against\n              <jats:italic>S. aureus<\/jats:italic>\n              . Isorhapontigenin effectively inhibits the hemolytic activity of\n              <jats:italic>S. aureus<\/jats:italic>\n              in a non-bactericidal manner. Additionally, it significantly reduces the cytotoxicity of\n              <jats:italic>S. aureus<\/jats:italic>\n              and impairs its ability to survive in macrophages. Mechanistically, isorhapontigenin modulates the expression of virulence factors, dose-dependently downregulating\n              <jats:italic>hla<\/jats:italic>\n              and upregulating the MgrA-regulated gene\n              <jats:italic>spa<\/jats:italic>\n              . Electrophoretic mobility shift assays demonstrated that isorhapontigenin inhibits the binding of MgrA to the\n              <jats:italic>hla<\/jats:italic>\n              promoter in a dose-dependent manner. Thermal shift assays confirmed the direct interaction between isorhapontigenin and the MgrA protein. The\n              <jats:italic>in vivo<\/jats:italic>\n              experiments demonstrated that isorhapontigenin significantly reduced the area of skin abscesses and improved survival in a pneumonia model while decreasing bacterial burden and inflammation in the lungs. In conclusion, isorhapontigenin holds potential as a candidate drug for further development as an anti-virulence agent for treating\n              <jats:italic>S. aureus<\/jats:italic>\n              infections.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              The emergence of antibiotic-resistant\n              <jats:italic>Staphylococcus aureus<\/jats:italic>\n              strains presents a formidable challenge to public health, necessitating novel approaches in combating these pathogens. Traditional antibiotics are becoming increasingly ineffective, leading to a pressing need for innovative therapeutic strategies. In this study, targeting virulence factors that play a crucial role in the pathogenesis of bacterial infections offers a promising alternative to circumvent resistance mechanisms. The discovery of isorhapontigenin as an inhibitor of\n              <jats:italic>S. aureus<\/jats:italic>\n              virulence represents a significant advance in anti-virulence therapy.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/msphere.00317-24","type":"journal-article","created":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T17:00:39Z","timestamp":1717606839000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":7,"title":["Exploring the potential of isorhapontigenin: attenuating\n            <i>Staphylococcus aureus<\/i>\n            virulence through MgrA-mediated regulation"],"prefix":"10.1128","volume":"9","author":[{"given":"Lei","family":"Yuan","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, Medical Center of Burn plastic and wound repair, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 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