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

二甲双胍逆转米诺环素通过破坏外膜、增强膜电位体外抑制耐米诺环素的鲍曼不动杆菌

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作者:Tingting Guo #, Xiaoli Sun #, Jie Yang, Liying Yang, Mengying Li, Yuhang Wang, Hongmei Jiao, Guocai Li

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.

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.

Results

The effect of metformin on the antibacterial activity of minocycline was determined by checkerboard and time-killing assay. 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.

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