ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Antimicrobials, Resistance and Chemotherapy
Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1586553
This article is part of the Research TopicPlant-derived Products for Developing New AntimicrobialsView all 3 articles
Rhein restores the sensitivity of mcr-1 carrying multidrug-resistant Escherichia coli to colistin
Provisionally accepted- 1Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan Province, China
- 2Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan Province, China
- 3College of Veterinary Medicine, Sichuan Agricultural University, Yaan Shi, China
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The emergence of the colistin resistance gene mcr-1 has resulted in a significant reduction in the clinical efficacy of colistin against infections caused by multidrug-resistant Gram-negative pathogens.A cost-effective approach for restoring the efficacy of antibiotics is to formulate synergistic antibiotic combinations with natural compounds that target the resistance of multidrug-resistant bacteria. In this study, we have demonstrated that rhein can effectively restore the sensitivity of mcr-1-positive Escherichia coli to colistin, both in vitro and in vivo. Mechanism studies have demonstrated that rhein primarily damages bacterial cell membranes, disrupts proton motive force, and generates excessive reactive oxygen species, and down-regulates the mcr-1 gene in E. coli. Compared to monotherapy, the combination of rhein and colistin greatly increased the survival rate of E. coli infected mice and significantly reduced the bacterial load in the viscera of the mice. Our results confirm that rhein serves as a promising adjuvant to colistin and, in combination with colistin, provides a viable approach to combat infections caused by colistin resistant E. coli.
Keywords: Rhein, Colistin, MCR-1, antibiotic adjuvant, antimicrobial resistance, Therapeutic effect
Received: 03 Mar 2025; Accepted: 28 May 2025.
Copyright: © 2025 Wang, Yang, Cao, Zhao, Song, Zhou, Jia, Zou, Li, Lv, Jing and Yin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Zhongqiong Yin, College of Veterinary Medicine, Sichuan Agricultural University, Yaan Shi, China
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