{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T19:10:33Z","timestamp":1782587433406,"version":"3.54.5"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T00:00:00Z","timestamp":1749513600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22377035"],"award-info":[{"award-number":["22377035"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["21977037"],"award-info":[{"award-number":["21977037"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2022A1515010674"],"award-info":[{"award-number":["2022A1515010674"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2023A1515011750"],"award-info":[{"award-number":["2023A1515011750"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Staphylococcus aureus poses a significant threat to human health, making it imperative to develop novel antimicrobial agents to combat infections caused by this pathogen.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To evaluate the antibacterial efficacy and elucidate the mechanism of bardoxolone as a potential agent against multidrug-resistant S. aureus.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Natural products and their derivatives were systematically evaluated for antibacterial activity. The antibacterial activity of bardoxolone was assessed in vitro against planktonic bacteria, internalized bacteria and biofilm-forming multidrug-resistant S. aureus, as well as in vivo using mouse pneumonia and thigh abscess infection models. The underlying antibacterial mechanisms were investigated through quantitative proteomics and a series of biochemical assays.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Bardoxolone exhibited potent antibacterial efficacy against S. aureus and other Gram-positive pathogens. It demonstrated strong antibacterial activity against internalized and biofilm-associated multidrug-resistant S. aureus, showing low resistance potential. In murine infection models, treatment significantly enhanced survival rates while reducing bacterial burden and attenuating inflammatory responses in pulmonary and femoral tissues. Mechanistic analyses revealed dual antibacterial actions: membrane integrity disruption and suppression of pyruvate metabolism, manifesting as diminished activity of pivotal enzymes, reduced acetyl-CoA\/ATP synthesis and consequent growth inhibition of S. aureus.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These findings suggest that bardoxolone holds promise as a candidate drug for treating refractory multidrug-resistant S. aureus infections.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkaf190","type":"journal-article","created":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T07:07:10Z","timestamp":1749539230000},"page":"2203-2213","source":"Crossref","is-referenced-by-count":1,"title":["Oleanolic acid derivative bardoxolone combats multidrug-resistant <i>Staphylococcus aureus<\/i> by destroying cell membrane and pyruvate metabolism pathway"],"prefix":"10.1093","volume":"80","author":[{"given":"Yun-Dan","family":"Zheng","sequence":"first","affiliation":[{"name":"MOE Key Laboratory of Tumor Molecular Biology and State Key Laboratory of Bioactive Molecules and Druggability Assessment, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University , Guangzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Xu","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Tumor Molecular Biology and State Key Laboratory of Bioactive Molecules and Druggability Assessment, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University , Guangzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Wu","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Tumor Molecular Biology and State Key Laboratory of Bioactive Molecules and Druggability Assessment, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University , Guangzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tairan","family":"Zhong","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Tumor Molecular Biology and State Key Laboratory of Bioactive Molecules and Druggability Assessment, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University , Guangzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing-Yu","family":"He","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Tumor Molecular Biology and State Key Laboratory of Bioactive Molecules and Druggability Assessment, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University , Guangzhou 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