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An alternative strategy to alleviate such a crisis is to identify promising compounds to restore antibiotics activity against MDR bacteria. It is reported that the antidiabetic drug metformin exhibits the potentiation effect on tetracycline antibiotics, particularly doxycycline and minocycline, against MDR <jats:italic>S. aureus<\/jats:italic>, <jats:italic>E. faecalis<\/jats:italic>, <jats:italic>E. coli<\/jats:italic>, and <jats:italic>S. enteritidis<\/jats:italic>. Mechanistic studies demonstrate that metformin promotes intracellular accumulation of doxycycline in tetracycline\u2010resistant <jats:italic>E. coli<\/jats:italic>. In addition, metformin boosts the immune response and alleviates the inflammatory responses in vitro. Last, metformin fully restores the activity of doxycycline in three animal infection models. Collectively, these results reveal the potential of metformin as a novel tetracyclines adjuvant to circumvent MDR bacterial pathogens and to improve the treatment outcome of recalcitrant infections.<\/jats:p>","DOI":"10.1002\/advs.201902227","type":"journal-article","created":{"date-parts":[[2020,5,12]],"date-time":"2020-05-12T10:55:26Z","timestamp":1589280926000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":199,"title":["Metformin Restores Tetracyclines Susceptibility against Multidrug Resistant Bacteria"],"prefix":"10.1002","volume":"7","author":[{"given":"Yuan","family":"Liu","sequence":"first","affiliation":[{"name":"Institute of Comparative Medicine College of Veterinary Medicine Yangzhou University  Yangzhou Jiangsu 225009 China"},{"name":"Jiangsu Co\u2010innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses  Yangzhou Jiangsu 225009 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