Rhein restores the sensitivity of mcr-1 carrying multidrug-resistant Escherichia coli to colistin
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 a...
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Frontiers Media S.A.
2025-06-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2025.1586553/full |
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| author | Nannan Wang Dan Yang Lijuan Cao Xinghong Zhao Xu Song Xun Zhou Renyong Jia Yuanfeng Zou Lixia Li Cheng Lv Bo Jing Zhongqiong Yin |
| author_facet | Nannan Wang Dan Yang Lijuan Cao Xinghong Zhao Xu Song Xun Zhou Renyong Jia Yuanfeng Zou Lixia Li Cheng Lv Bo Jing Zhongqiong Yin |
| author_sort | Nannan Wang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-dd8f54f422544f0f80ca7fa98931689a |
| institution | OA Journals |
| issn | 1664-302X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj-art-dd8f54f422544f0f80ca7fa98931689a2025-08-20T02:06:39ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2025-06-011610.3389/fmicb.2025.15865531586553Rhein restores the sensitivity of mcr-1 carrying multidrug-resistant Escherichia coli to colistinNannan Wang0Dan Yang1Lijuan Cao2Xinghong Zhao3Xu Song4Xun Zhou5Renyong Jia6Yuanfeng Zou7Lixia Li8Cheng Lv9Bo Jing10Zhongqiong Yin11Department of Pharmacy, Natural Medicine Research Center, Sichuan Agricultural University, Chengdu, ChinaDepartment of Pharmacy, Natural Medicine Research Center, Sichuan Agricultural University, Chengdu, ChinaDepartment of Pharmacy, Natural Medicine Research Center, Sichuan Agricultural University, Chengdu, ChinaDepartment of Pharmacy, Natural Medicine Research Center, Sichuan Agricultural University, Chengdu, ChinaDepartment of Pharmacy, Natural Medicine Research Center, Sichuan Agricultural University, Chengdu, ChinaDepartment of Pharmacy, Natural Medicine Research Center, Sichuan Agricultural University, Chengdu, ChinaKey Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, ChinaDepartment of Pharmacy, Natural Medicine Research Center, Sichuan Agricultural University, Chengdu, ChinaDepartment of Pharmacy, Natural Medicine Research Center, Sichuan Agricultural University, Chengdu, ChinaDepartment of Pharmacy, Natural Medicine Research Center, Sichuan Agricultural University, Chengdu, ChinaDepartment of Pharmacy, Natural Medicine Research Center, Sichuan Agricultural University, Chengdu, ChinaDepartment of Pharmacy, Natural Medicine Research Center, Sichuan Agricultural University, Chengdu, ChinaThe 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.https://www.frontiersin.org/articles/10.3389/fmicb.2025.1586553/fullrheincolistinmcr-1antibiotic adjuvantantimicrobial resistancetherapeutic effect |
| spellingShingle | Nannan Wang Dan Yang Lijuan Cao Xinghong Zhao Xu Song Xun Zhou Renyong Jia Yuanfeng Zou Lixia Li Cheng Lv Bo Jing Zhongqiong Yin Rhein restores the sensitivity of mcr-1 carrying multidrug-resistant Escherichia coli to colistin Frontiers in Microbiology rhein colistin mcr-1 antibiotic adjuvant antimicrobial resistance therapeutic effect |
| title | Rhein restores the sensitivity of mcr-1 carrying multidrug-resistant Escherichia coli to colistin |
| title_full | Rhein restores the sensitivity of mcr-1 carrying multidrug-resistant Escherichia coli to colistin |
| title_fullStr | Rhein restores the sensitivity of mcr-1 carrying multidrug-resistant Escherichia coli to colistin |
| title_full_unstemmed | Rhein restores the sensitivity of mcr-1 carrying multidrug-resistant Escherichia coli to colistin |
| title_short | Rhein restores the sensitivity of mcr-1 carrying multidrug-resistant Escherichia coli to colistin |
| title_sort | rhein restores the sensitivity of mcr 1 carrying multidrug resistant escherichia coli to colistin |
| topic | rhein colistin mcr-1 antibiotic adjuvant antimicrobial resistance therapeutic effect |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2025.1586553/full |
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