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Metformin Restores Tetracyclines Susceptibility against Multidrug Resistant Bacteria.

ABSTRACT: 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.

SUBMITTER: Liu Y

PROVIDER: S-EPMC7312304 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Metformin Restores Tetracyclines Susceptibility against Multidrug Resistant Bacteria.

Liu Yuan Y Jia Yuqian Y Yang Kangni K Li Ruichao R Xiao Xia X Zhu Kui K Wang Zhiqiang Z

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20200512 12

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. ente ...[more]

PMID: 32596101

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Project description:BackgroundThe "One Health" concept recognizes that human health and animal health are interdependent and bound to the health of the ecosystem in which they (co)exist. This interconnection favors the transmission of bacteria and other infectious agents as well as the flow of genetic elements containing antibiotic resistance genes. This problem is worsened when pathogenic bacteria have the ability to establish as biofilms. Therefore, it is important to understand the characteristics and behaviour of microorganisms in both planktonic and biofilms states from the most diverse environmental niches to mitigate the emergence and dissemination of resistance.MethodsThe purpose of this work was to assess the antibiotic susceptibility of four bacteria (Acinetobacter spp., Klebsiella pneumoniae, Pseudomonas fluorescens and Shewanella putrefaciens) isolated from wild animals and their ability to form biofilms. The effect of two antibiotics, imipenem (IPM) and ciprofloxacin (CIP), on biofilm removal was also assessed. Screening of resistance genetic determinants was performed by PCR. Biofilm tests were performed by a modified microtiter plate method. Bacterial surface hydrophobicity was determined by sessile drop contact angles.ResultsThe susceptibility profile classified the bacteria as multidrug-resistant. Three genes coding for ?-lactamases were detected in K. pneumoniae (TEM, SHV, OXA-aer) and one in P. fluorescens (OXA-aer). K. pneumoniae was the microorganism that carried more ?-lactamase genes and it was the most proficient biofilm producer, while P. fluorescens demonstrated the highest adhesion ability. Antibiotics at their MIC, 5 × MIC and 10 × MIC were ineffective in total biofilm removal. The highest biomass reductions were found with IPM (54% at 10 × MIC) against K. pneumoniae biofilms and with CIP (40% at 10 × MIC) against P. fluorescens biofilms.DiscussionThe results highlight wildlife as important host reservoirs and vectors for the spread of multidrug-resistant bacteria and genetic determinants of resistance. The ability of these bacteria to form biofilms should increase their persistence.

Dataset Information

Metformin Restores Tetracyclines Susceptibility against Multidrug Resistant Bacteria.

Publications

Metformin Restores Tetracyclines Susceptibility against Multidrug Resistant Bacteria.

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