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Natural products dominate the preferred chemical scaffolds for the discovery of antibacterial agents. Here, the potential of natural flavonoids from plants against MDR bacteria, is demonstrated. Structure\u2013activity relationship analysis shows the prenylation modulates the activity of flavonoids and obtains two compounds,\n                    <jats:italic>\u03b1<\/jats:italic>\n                    \u2010mangostin (AMG) and isobavachalcone (IBC). AMG and IBC not only display rapid bactericidal activity against Gram\u2010positive bacteria, but also restore the susceptibility of colistin against Gram\u2010negative pathogens. Mechanistic studies generally show such compounds bind to the phospholipids of bacterial membrane, and result in the dissipation of proton motive force and metabolic perturbations, through distinctive modes of action. The efficacy of AMG and IBC in four models associated with infection or contamination, is demonstrated. These results suggest that natural products of plants may be a promising and underappreciated reservoir to circumvent the existing antibiotic resistance.\n                  <\/jats:p>","DOI":"10.1002\/advs.202100749","type":"journal-article","created":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T00:20:54Z","timestamp":1622074854000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":375,"title":["Plant Natural Flavonoids Against Multidrug Resistant Pathogens"],"prefix":"10.1002","volume":"8","author":[{"given":"Meirong","family":"Song","sequence":"first","affiliation":[{"name":"National Center for Veterinary Drug Safety Evaluation College of Veterinary Medicine China Agricultural University  Beijing 100193 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Liu","sequence":"additional","affiliation":[{"name":"National Center for Veterinary Drug Safety Evaluation College of Veterinary Medicine China Agricultural University  Beijing 100193 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Li","sequence":"additional","affiliation":[{"name":"National Center for Veterinary Drug Safety Evaluation College of Veterinary Medicine China Agricultural University  Beijing 100193 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojia","family":"Liu","sequence":"additional","affiliation":[{"name":"National Center for Veterinary Drug Safety Evaluation College of Veterinary Medicine China Agricultural University  Beijing 100193 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihui","family":"Hao","sequence":"additional","affiliation":[{"name":"Center of Research and Innovation of Chinese Traditional Veterinary Medicine China Agricultural University  Beijing 100193 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Agricultural University  Beijing 100193 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianzhong","family":"Shen","sequence":"additional","affiliation":[{"name":"National Center for Veterinary Drug Safety Evaluation College of Veterinary Medicine China Agricultural University  Beijing 100193 China"},{"name":"Beijing Key Laboratory of Detection Technology for Animal\u2010Derived Food Safety and Beijing Laboratory for Food Quality and Safety China Agricultural University  Beijing 100193 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