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Emergence of colistin resistance in microbes is a critical challenge. Herein, curcumin is discovered, for the first time, to reverse the resistance phenotype of colistin\u2010resistant bacteria via a checkerboard assay. For the co\u2010delivery of curcumin and colistin, negatively charged poly(ethylene glycol)\u2010functionalized liposomes encapsulating both drugs (Lipo\u2010cc) are prepared. Killing kinetics and live\/dead assays confirm the antibacterial activity of Lipo\u2010cc against colistin\u2010resistant bacteria, which is more potent than that of the free curcumin and colistin combination. Mechanistical studies reveal that Lipo\u2010cc restores the affinity of colistin for the bacterial membrane and improves the uptake of curcumin, which leads to reduced efflux pump activity, achieving a synergistic effect of colistin and curcumin. At the effective antibacterial dose, Lipo\u2010cc does not exhibit any toxicity. The therapeutic efficacy of Lipo\u2010cc is further demonstrated in an intestinal bacterial infection model induced with colistin\u2010resistant <jats:italic>Escherichia coli<\/jats:italic>. Lipo\u2010cc reduces the bacterial burden with over 6\u2010log reduction and alleviated inflammation caused by infection. Importantly, unlike colistin, Lipo\u2010cc does not affect the homeostasis of the intestinal flora. Taken together, Lipo\u2010cc successfully overcame colistin resistance, indicating its potential for the treatment of colistin\u2010resistant bacterial infections.<\/jats:p>","DOI":"10.1002\/adhm.202202903","type":"journal-article","created":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T11:28:07Z","timestamp":1690802887000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Liposomes Co\u2010Delivering Curcumin and Colistin to Overcome Colistin Resistance in Bacterial Infections"],"prefix":"10.1002","volume":"12","author":[{"given":"Chengyuan","family":"Qin","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences (Shenzhen) Shenzhen Campus of Sun Yat\u2010sen University  518107 Shenzhen P. R. 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