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二甲双胍逆转米诺环素耐药鲍曼不动杆菌的作用机制是破坏外膜并增加膜电位体外。

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

机构信息

Department of Microbiology, Medical College, Yangzhou University, Yangzhou, 225001, China.

Jiangsu Key Laboratory of Zoonosis/Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, 225009, China.

出版信息

BMC Microbiol. 2022 Sep 12;22(1):215. doi: 10.1186/s12866-022-02629-4.

DOI:10.1186/s12866-022-02629-4
PMID:36089583
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9465895/
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-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.

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.

摘要

背景

鲍曼不动杆菌（A.baumannii）是一种机会致病菌，已成为最麻烦的病原体之一。全球范围内都有报道称 A.baumannii 存在耐药性。米诺环素被发现对多药耐药的 A.baumannii 具有活性，并已获得 FDA 批准用于治疗敏感株 A.baumannii 引起的感染。然而，米诺环素耐药性的出现及其毒副作用仍需解决。因此，本研究旨在评估二甲双胍与米诺环素联合应用对米诺环素耐药的 A.baumannii 的协同作用。

结果

通过棋盘法和时间杀伤试验确定了二甲双胍对米诺环素抗菌活性的影响。此外，通过生物膜形成试验观察到二甲双胍与米诺环素联合使用可以抑制生物膜的形成。监测外膜完整性、膜通透性、膜电位和活性氧（ROS），以探讨二甲双胍对米诺环素协同作用的潜在机制。结果表明，二甲双胍可以破坏 A.baumannii 的外膜，增强其膜电位，但不影响膜通透性和 ROS。

结论

这些发现表明，二甲双胍和米诺环素联合使用有可能恢复米诺环素对米诺环素耐药的 A.baumannii 的活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec55/9465895/04e9b2afcbf9/12866_2022_2629_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec55/9465895/2894f7001deb/12866_2022_2629_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec55/9465895/e59d7630caed/12866_2022_2629_Fig4_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec55/9465895/3173989e5f14/12866_2022_2629_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec55/9465895/ea1091c3c465/12866_2022_2629_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec55/9465895/dffa6b2e9213/12866_2022_2629_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec55/9465895/04e9b2afcbf9/12866_2022_2629_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec55/9465895/2894f7001deb/12866_2022_2629_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec55/9465895/41618c82724b/12866_2022_2629_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec55/9465895/2d9e7adf2936/12866_2022_2629_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec55/9465895/e59d7630caed/12866_2022_2629_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec55/9465895/c9779cc005be/12866_2022_2629_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec55/9465895/3173989e5f14/12866_2022_2629_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec55/9465895/ea1091c3c465/12866_2022_2629_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec55/9465895/dffa6b2e9213/12866_2022_2629_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec55/9465895/04e9b2afcbf9/12866_2022_2629_Fig9_HTML.jpg

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