{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T05:21:08Z","timestamp":1787721668417,"version":"build-2784847793"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>\n                    Amid the growing antibiotic resistance crisis, colistin remains a last-line therapeutic option for multidrug-resistant (MDR) Gram-negative bacterial infections. However, the emergence and rapid dissemination of plasmid-mediated colistin resistance gene (\n                    <jats:italic>mcr<\/jats:italic>\n                    ) have markedly reduced its clinical effectiveness. Utilizing colistin adjuvants to restore its antibacterial potency is a promising strategy to combat this threat. In this study, we aimed to investigate the synergistic effects of \u03b1-terpineol in combination with colistin against colistin-resistant MDR\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    (\n                    <jats:italic>E. coli<\/jats:italic>\n                    ) and to elucidate the underlying mechanisms of this synergy.\n                    <jats:italic>In vitro<\/jats:italic>\n                    synergistic activity was evaluated using checkerboard microdilution assays, time-kill curve analyses, and resistance development studies. Mechanistic insights were obtained through transcriptomic analysis and fluorescence-probe based assays.\n                    <jats:italic>In vivo<\/jats:italic>\n                    efficacy was validated using\n                    <jats:italic>Galleria mellonella<\/jats:italic>\n                    and mouse acute peritonitis infection models. The results showed that the combination of \u03b1-terpineol and colistin exhibited synergistic bactericidal activity and suppressed the development of colistin resistance. \u03b1-Terpineol increased inner- and outer-membrane fluidity in\n                    <jats:italic>E. coli<\/jats:italic>\n                    , thereby enhancing colistin uptake. Furthermore, it inhibited superoxide dismutase (SOD) activity, preventing the conversion of O\n                    <jats:sub>2<\/jats:sub>\n                    <jats:sup>\u00b7\u2013<\/jats:sup>\n                    to H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    and causing superoxide accumulation. Elevated O\n                    <jats:sub>2<\/jats:sub>\n                    <jats:sup>\u00b7\u2013<\/jats:sup>\n                    levels damaged iron\u2013sulfur clusters and impaired respiratory function. Together with the proton motive force (PMF) dissipation, these effects severely impaired ATP synthesis, ultimately sensitizing MDR\n                    <jats:italic>E. coli<\/jats:italic>\n                    to colistin. The combination also showed significant therapeutic efficacy in animal models. Our findings identify \u03b1-terpineol as a promising colistin adjuvant that restores antibacterial activity by disrupting membrane integrity and impairing antioxidant defenses, offering a viable strategy for treating MDR Gram-negative bacterial infections.\n                  <\/jats:p>","DOI":"10.3389\/fcimb.2026.1908346","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T04:53:28Z","timestamp":1787720008000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["\u03b1-Terpineol reverses mcr-mediated colistin resistance and potentiates colistin\u2019s antibacterial activity in multidrug-resistant Escherichia coli"],"prefix":"10.3389","volume":"16","author":[{"given":"Yujuan","family":"Li","sequence":"first","affiliation":[{"name":"College of Basic Medicine, Xiangnan University","place":["Chenzhou, China"]},{"name":"Hunan Provincial Key Laboratory of Gut Microbiota and Chronic Disease Intervention","place":["Chenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Basic Medicine, Xiangnan University","place":["Chenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Zhou","sequence":"additional","affiliation":[{"name":"College of Clinical, Xiangnan University","place":["Chenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhou","sequence":"additional","affiliation":[{"name":"College of Clinical, Xiangnan University","place":["Chenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Hu","sequence":"additional","affiliation":[{"name":"College of Basic Medicine, Xiangnan University","place":["Chenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangshuang","family":"Liang","sequence":"additional","affiliation":[{"name":"College of Clinical, Xiangnan University","place":["Chenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhua","family":"Xie","sequence":"additional","affiliation":[{"name":"College of Basic Medicine, Xiangnan University","place":["Chenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Cheng","sequence":"additional","affiliation":[{"name":"College of Basic Medicine, Xiangnan University","place":["Chenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yachao","family":"Jiang","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Xiangnan University","place":["Chenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Jiang","sequence":"additional","affiliation":[{"name":"College of Basic Medicine, Xiangnan University","place":["Chenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Liu","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory of Gut Microbiota and Chronic Disease Intervention","place":["Chenzhou, China"]},{"name":"College of Pharmacy, Xiangnan University","place":["Chenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","article-title":"GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers","author":"Abraham","year":"2015","journal-title":"Softwarex"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.2174\/1871526523666230725103902","article-title":"An overview of the global alarming increase of multiple drug resistant: A major challenge in clinical diagnosis","volume":"24","author":"Alara","year":"2024","journal-title":"Infect. 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