MCR-1-dependent lipid remodelling compromises the viability of Gram-negative bacteria
The global dissemination of the mobilized colistin resistance gene, mcr-1, threatens human health. Recent studies by our group and others have shown that the withdrawal of colistin as a feed additive dramatically reduced the prevalence of mcr-1. Although it is accepted that the rapid reduction in mc...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2022-12-01
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| Series: | Emerging Microbes and Infections |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2022.2065934 |
| _version_ | 1818015875390767104 |
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| author | Siyuan Feng Wanfei Liang Jiachen Li Yong Chen Dianrong Zhou Lujie Liang Daixi Lin Yaxin Li Hui Zhao Huihui Du Min Dai Li-Na Qin Fan Bai Yohei Doi Lan-Lan Zhong Guo-bao Tian |
| author_facet | Siyuan Feng Wanfei Liang Jiachen Li Yong Chen Dianrong Zhou Lujie Liang Daixi Lin Yaxin Li Hui Zhao Huihui Du Min Dai Li-Na Qin Fan Bai Yohei Doi Lan-Lan Zhong Guo-bao Tian |
| author_sort | Siyuan Feng |
| collection | DOAJ |
| description | The global dissemination of the mobilized colistin resistance gene, mcr-1, threatens human health. Recent studies by our group and others have shown that the withdrawal of colistin as a feed additive dramatically reduced the prevalence of mcr-1. Although it is accepted that the rapid reduction in mcr-1 prevalence may have resulted, to some extent, from the toxic effects of MCR-1, the detailed mechanism remains unclear. Here, we found that MCR-1 damaged the outer membrane (OM) permeability in Escherichia coli and Klebsiella pneumonia and that this event was associated with MCR-1-mediated cell shrinkage and death during the stationary phase. Notably, the capacity of MCR-1-expressing cells for recovery from the stationary phase under improved conditions was reduced in a time-dependent manner. We also showed that mutations in the potential lipid-A-binding pocket of MCR-1, but not in the catalytic domain, restored OM permeability and cell viability. During the stationary phase, PbgA, a sensor of periplasmic lipid-A and LpxC production that performed the first step in lipid-A synthesis, was reduced after MCR-1 expression, suggesting that MCR-1 disrupted lipid homeostasis. Consistent with this, the overexpression of LpxC completely reversed the MCR-1-induced OM permeability defect. We propose that MCR-1 causes lipid remodelling that results in an OM permeability defect, thus compromising the viability of Gram-negative bacteria. These findings extended our understanding of the effect of MCR-1 on bacterial physiology and provided a potential strategy for eliminating drug-resistant bacteria. |
| first_indexed | 2024-04-14T07:03:37Z |
| format | Article |
| id | doaj.art-5fb7a8fb55204db2aa092eccaa617b39 |
| institution | Directory Open Access Journal |
| issn | 2222-1751 |
| language | English |
| last_indexed | 2024-04-14T07:03:37Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj.art-5fb7a8fb55204db2aa092eccaa617b392022-12-22T02:06:39ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512022-12-011111236124910.1080/22221751.2022.2065934MCR-1-dependent lipid remodelling compromises the viability of Gram-negative bacteriaSiyuan Feng0Wanfei Liang1Jiachen Li2Yong Chen3Dianrong Zhou4Lujie Liang5Daixi Lin6Yaxin Li7Hui Zhao8Huihui Du9Min Dai10Li-Na Qin11Fan Bai12Yohei Doi13Lan-Lan Zhong14Guo-bao Tian15Program in Pathobiology, The Fifth Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangdong, People’s Republic of ChinaProgram in Pathobiology, The Fifth Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangdong, People’s Republic of ChinaProgram in Pathobiology, The Fifth Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangdong, People’s Republic of ChinaSchool of Laboratory Medicine, Chengdu Medical College, Chengdu, People’s Republic of ChinaProgram in Pathobiology, The Fifth Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangdong, People’s Republic of ChinaProgram in Pathobiology, The Fifth Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangdong, People’s Republic of ChinaProgram in Pathobiology, The Fifth Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangdong, People’s Republic of ChinaProgram in Pathobiology, The Fifth Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangdong, People’s Republic of ChinaGuangdong Provincial Key Laboratory of Biotechnology for Plant Development, School of Life Sciences, South China Normal University, Guangzhou, People’s Republic of ChinaCollege of Biology and Food Engineering, Chongqing Three Gorges University, Chongqing, People’s Republic of ChinaSchool of Laboratory Medicine, Chengdu Medical College, Chengdu, People’s Republic of ChinaDepartment of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, People’s Republic of ChinaBiomedical Pioneering Innovation Center (BIOPIC), School of Life Sciences, Peking University, Beijing, People's Republic of ChinaUniversity of Pittsburgh School of Medicine, Pittsburgh, PA, USAProgram in Pathobiology, The Fifth Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangdong, People’s Republic of ChinaProgram in Pathobiology, The Fifth Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangdong, People’s Republic of ChinaThe global dissemination of the mobilized colistin resistance gene, mcr-1, threatens human health. Recent studies by our group and others have shown that the withdrawal of colistin as a feed additive dramatically reduced the prevalence of mcr-1. Although it is accepted that the rapid reduction in mcr-1 prevalence may have resulted, to some extent, from the toxic effects of MCR-1, the detailed mechanism remains unclear. Here, we found that MCR-1 damaged the outer membrane (OM) permeability in Escherichia coli and Klebsiella pneumonia and that this event was associated with MCR-1-mediated cell shrinkage and death during the stationary phase. Notably, the capacity of MCR-1-expressing cells for recovery from the stationary phase under improved conditions was reduced in a time-dependent manner. We also showed that mutations in the potential lipid-A-binding pocket of MCR-1, but not in the catalytic domain, restored OM permeability and cell viability. During the stationary phase, PbgA, a sensor of periplasmic lipid-A and LpxC production that performed the first step in lipid-A synthesis, was reduced after MCR-1 expression, suggesting that MCR-1 disrupted lipid homeostasis. Consistent with this, the overexpression of LpxC completely reversed the MCR-1-induced OM permeability defect. We propose that MCR-1 causes lipid remodelling that results in an OM permeability defect, thus compromising the viability of Gram-negative bacteria. These findings extended our understanding of the effect of MCR-1 on bacterial physiology and provided a potential strategy for eliminating drug-resistant bacteria.https://www.tandfonline.com/doi/10.1080/22221751.2022.2065934MCR-1outer membrane (OM) permeabilityviabilitylipid homeostasiscolistin |
| spellingShingle | Siyuan Feng Wanfei Liang Jiachen Li Yong Chen Dianrong Zhou Lujie Liang Daixi Lin Yaxin Li Hui Zhao Huihui Du Min Dai Li-Na Qin Fan Bai Yohei Doi Lan-Lan Zhong Guo-bao Tian MCR-1-dependent lipid remodelling compromises the viability of Gram-negative bacteria Emerging Microbes and Infections MCR-1 outer membrane (OM) permeability viability lipid homeostasis colistin |
| title | MCR-1-dependent lipid remodelling compromises the viability of Gram-negative bacteria |
| title_full | MCR-1-dependent lipid remodelling compromises the viability of Gram-negative bacteria |
| title_fullStr | MCR-1-dependent lipid remodelling compromises the viability of Gram-negative bacteria |
| title_full_unstemmed | MCR-1-dependent lipid remodelling compromises the viability of Gram-negative bacteria |
| title_short | MCR-1-dependent lipid remodelling compromises the viability of Gram-negative bacteria |
| title_sort | mcr 1 dependent lipid remodelling compromises the viability of gram negative bacteria |
| topic | MCR-1 outer membrane (OM) permeability viability lipid homeostasis colistin |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2022.2065934 |
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