Highly persistent incidence of multidrug resistant (MDR) bacterial pathogens constitutes a global burden for public health. 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 S. aureus , E. faecalis , E. coli , and S. enteritidis . Mechanistic studies demonstrate that metformin promotes intracellular accumulation of doxycycline in tetracycline‐resistant E. coli . 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.

中文翻译：

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二甲双胍可恢复四环素对多重耐药细菌的敏感性。

多重耐药（MDR）细菌病原体的高持续发病率构成了全球公共卫生的负担。缓解这种危机的另一种策略是寻找有前景的化合物来恢复针对耐多药细菌的抗生素活性。据报道，抗糖尿病药物二甲双胍对四环素类抗生素，尤其是强力霉素和米诺环素，对耐多药金黄色葡萄球菌、粪肠球菌、大肠杆菌和肠炎沙门氏菌具有增强作用。机制研究表明，二甲双胍促进四环素耐药大肠杆菌细胞内多西环素的积累。此外，二甲双胍在体外可增强免疫反应并减轻炎症反应。最后，二甲双胍在三种动物感染模型中完全恢复强力霉素的活性。总的来说，这些结果揭示了二甲双胍作为新型四环素佐剂规避 MDR 细菌病原体并改善顽固性感染治疗结果的潜力。