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Further mechanistic analysis demonstrated that these flavonoids are able to disrupt bacterial iron homeostasis through converting ferric iron to ferrous form. The excessive intracellular ferrous iron modulated the membrane charge of bacteria via interfering the two-component system\n                    <jats:italic>pmrA<\/jats:italic>\n                    \/\n                    <jats:italic>pmrB<\/jats:italic>\n                    , thereby promoting the colistin binding and subsequent membrane damage. The potentiation of these flavonoids was further confirmed in an in vivo infection model. Collectively, the current study provided three flavonoids as colistin adjuvant to replenish our arsenals for combating bacterial infections and shed the light on the bacterial iron signaling as a promising target for antibacterial therapies.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adg4205","type":"journal-article","created":{"date-parts":[[2023,6,9]],"date-time":"2023-06-09T13:58:28Z","timestamp":1686319108000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":130,"title":["Natural flavonoids disrupt bacterial iron homeostasis to potentiate colistin efficacy"],"prefix":"10.1126","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5375-6037","authenticated-orcid":true,"given":"Zi-xing","family":"Zhong","sequence":"first","affiliation":[{"name":"Guangdong Laboratory for Lingnan Modern Agriculture, National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of 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