Your new experience awaits. Try the new design now and help us make it even better

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
Nannan  WangNannan Wang1Dan  YangDan Yang1Lijuan  CaoLijuan Cao1Xinghong  ZhaoXinghong Zhao1Xu  SongXu Song1Xun  ZhouXun Zhou1Renyong  JiaRenyong Jia2Yuanfeng  ZouYuanfeng Zou1Lixia  LiLixia Li1Cheng  LvCheng Lv1Bo  JingBo Jing1Zhongqiong  YinZhongqiong Yin3*
  • 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

The final, formatted version of the article will be published soon.

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

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.