Synergistic Activity of Tetrandrine and Colistin against mcr-1-Harboring Escherichia coli
-
Published:2022-10-02
Issue:10
Volume:11
Page:1346
-
ISSN:2079-6382
-
Container-title:Antibiotics
-
language:en
-
Short-container-title:Antibiotics
Author:
Shafiq MuhammadORCID, Yao FenORCID, Bilal HazratORCID, Rahman Sadeeq UrORCID, Zeng Mi, Ali IlyasORCID, Zeng Yuebin, Li Xin, Yuan Yumeng, Jiao Xiaoyang
Abstract
Before the emergence of plasmid-mediated colistin resistance, colistin was once considered the last drug of choice for infections caused by carbapenem-resistant bacteria. Currently, researchers are relentlessly exploring possible alternative therapies that could efficiently curb the spread of drug resistance. In this study, we aim to investigate the synergistic antibacterial activity of tetrandrine in combination with colistin against mcr-1-harboring Escherichia coli. We examined the antibacterial activity of tetrandrine in combination with colistin in vivo and in vitro and examined the bacterial cells by fluorescence, scanning, and transmission electron microscopy (TEM) to explore their underlying mechanism of action. We further performed a computational analysis of MCR-1 protein and tetrandrine to determine the interaction interface of these two molecules. We confirmed that neither colistin nor tetrandrine could, on their own, inhibit the growth of mcr-1-positive E. coli. However, in combination, tetrandrine synergistically enhanced colistin activity to inhibit the growth of E. coli both in vivo and in vitro. Similarly, molecular docking showed that tetrandrine interacted with the three crucial amino acids of the MCR-1 protein in the active site, which might inhibit MCR-1 from binding to its substrates, cause MCR-1 to lose its ability to confer resistance. This study confirmed that tetrandrine and colistin have the ability to synergistically overcome the issue of colistin resistance in mcr-1-harboring E. coli.
Funder
National Natural Science Foundation of China Li Ka Shing Foundation
Subject
Pharmacology (medical),Infectious Diseases,Microbiology (medical),General Pharmacology, Toxicology and Pharmaceutics,Biochemistry,Microbiology
Reference49 articles.
1. Current Trends in Antimicrobial Resistance of Escherichia coli;Paitan;Curr. Top. Microbiol. Immunol.,2018 2. Zhang, Q., Chen, S., Liu, X., Lin, W., and Zhu, K. Equisetin Restores Colistin Sensitivity against Multi-Drug Resistant Gram-Negative Bacteria. Antibiotics, 2021. 10. 3. Ejaz, H., Younas, S., Qamar, M.U., Junaid, K., Abdalla, A.E., Abosalif, K.O.A., Alameen, A.A.M., Elamir, M.Y.M., Ahmad, N., and Hamam, S.S.M. Molecular epidemiology of extensively drug-resistant mcr encoded colistin-resistant bacterial strains co-expressing multifarious β-lactamases. Antibiotics, 2021. 10. 4. Ejaz, H., Younas, S., Abosalif, K.O., Junaid, K., Alzahrani, B., Alsrhani, A., Abdalla, A.E., Ullah, M.I., Qamar, M.U., and Hamam, S.S. Molecular analysis of bla SHV, bla TEM, and bla CTX-M in extended-spectrum β-lactamase producing Enterobacteriaceae recovered from fecal specimens of animals. PLoS ONE, 2021. 16. 5. Extended-spectrum β-lactamases: An update on their characteristics, epidemiology and detection;Castanheira;JAC-Antimicrob. Resist.,2021
Cited by
4 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|