Metformin reverse minocycline to inhibit minocycline-resistant Acinetobacter baumannii by destroy the outer membrane and enhance membrane potential in vitro

Abstract Background: Acinetobacter baumannii (A. baumannii) is an opportunistic pathogen and has emerged as one of the most troublesome pathogens. Drug resistance in A. baumannii has been reported on a global scale. Minocycline was found to be active against multi-drug resistant A. baumannii and was approved by the FDA for the infections caused by sensitive strains of A. baumannii. However, the emergence of minocycline resistance and its toxic effects still need to be addressed. Therefore, this study aimed to evaluate the synergistic effects of metformin combined with minocycline on minocycline-resistant A. baumannii. Results: The effect of metformin on the antibacterial activity of minocycline was determined by checkerboard and time-kill assays. Further, it was observed by biofilm formation assay that metformin combination with minocycline can inhibit the formation of biofilm. Outer membrane integrity, membrane permeability, membrane potential and reactive oxygen species (ROS) were monitored to explore the underlying synergistic mechanisms of metformin on minocycline. And the results shown that metformin can destroy the outer membrane of A. baumannii, enhance its membrane potential, but does not affect the membrane permeability and ROS.Conclusion: These findings suggested that the combination of metformin and minocycline has the potential for rejuvenating the activity of minocycline against minocycline-resistant A. baumannii.