Open AccessMetformin Restores Tetracyclines Susceptibility against Multidrug Resistant Bacteria
Author(s) -
Liu Yuan,
Jia Yuqian,
Yang Kangni,
Li Ruichao,
Xiao Xia,
Zhu Kui,
Wang Zhiqiang
Publication year - 2020
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.201902227
Subject(s) - doxycycline , metformin , minocycline , tetracycline , antibiotics , multiple drug resistance , microbiology and biotechnology , pharmacology , biology , medicine , insulin
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.