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Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The continuous emergence and spread of polymyxin-resistant <jats:italic>Acinetobacter baumannii<\/jats:italic> pose a significant global health challenge, necessitating the development of novel therapeutic strategies. Aloe, with its long-standing history of medicinal use, has recently been the subject of substantial research for its efficacy against pathogenic infections.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study investigates the potential application of anthraquinone components in aloe against polymyxin-resistant <jats:italic>A. baumannii<\/jats:italic> by liquid chromatography-mass spectrometry, in vitro activity assessment, and construction of animal infection models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The findings demonstrate that aloe emodin, emodin, rhein, and their mixtures in equal mass ratios (EAR) exhibit strain-specific antibacterial activities against polymyxin-resistant <jats:italic>A. baumannii<\/jats:italic>. Co-administration of EAR with EDTA synergistically and universally enhanced the antibacterial activity and bactericidal efficacy of polymyxins against polymyxin-resistant <jats:italic>A. baumannii<\/jats:italic>, while also reducing the frequency of polymyxin-resistant mutations in polymyxinssensitive <jats:italic>A. baumannii<\/jats:italic>. Following toxicity assessment on human hepatic and renal cell lines, the combination therapy was applied to skin wounds in mice infected with polymyxin-resistant <jats:italic>A. baumannii<\/jats:italic>. Compared to monotherapy, the combination therapy significantly accelerated wound healing and reduced bacterial burden.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The combination of EAR and EDTA with polymyxins offers a novel therapeutic approach for managing skin infections caused by polymyxinresistant <jats:italic>A. baumannii<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2024.1467607","type":"journal-article","created":{"date-parts":[[2024,9,13]],"date-time":"2024-09-13T13:39:26Z","timestamp":1726234766000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Combination of aloe emodin, emodin, and rhein from Aloe with EDTA sensitizes the resistant Acinetobacter baumannii to polymyxins"],"prefix":"10.3389","volume":"14","author":[{"given":"Yue","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinping","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqing","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongwei","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhua","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalei","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuandong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,9,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"106104","DOI":"10.1016\/j.ijantimicag.2020.106104","article-title":"Management of infections caused by WHO critical priority Gram-negative pathogens in Arab countries of the Middle East: a consensus paper","volume":"56","author":"Al Salman","year":"2020","journal-title":"Int. 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