Colistin Resistance Gene mcr-1 Mediates Cell Permeability and Resistance to Hydrophobic Antibiotics
Colistin is considered the last-resort antibiotic used to treat multidrug resistant bacteria-related infections. However, the discovery of the plasmid-mediated colistin resistance gene, mcr-1, threatens the clinical utility of colistin antibiotics. In this study, the physiological function of MCR-1,...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-01-01
|
| Series: | Frontiers in Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2019.03015/full |
| _version_ | 1819041758496948224 |
|---|---|
| author | Baiyuan Li Fang Yin Xuanyu Zhao Xuanyu Zhao Yunxue Guo Weiquan Wang Weiquan Wang Pengxia Wang Honghui Zhu Yeshi Yin Xiaoxue Wang Xiaoxue Wang |
| author_facet | Baiyuan Li Fang Yin Xuanyu Zhao Xuanyu Zhao Yunxue Guo Weiquan Wang Weiquan Wang Pengxia Wang Honghui Zhu Yeshi Yin Xiaoxue Wang Xiaoxue Wang |
| author_sort | Baiyuan Li |
| collection | DOAJ |
| description | Colistin is considered the last-resort antibiotic used to treat multidrug resistant bacteria-related infections. However, the discovery of the plasmid-mediated colistin resistance gene, mcr-1, threatens the clinical utility of colistin antibiotics. In this study, the physiological function of MCR-1, which encodes an LPS-modifying enzyme, was investigated in E. coli K-12. Specifically, the impact of mcr-1 on membrane permeability and antibiotic resistance of E. coli was assessed by constructing an mcr-1 deletion mutant and by a complementation study. The removal of the mcr-1 gene from plasmid pHNSHP45 not only led to reduced resistance to colistin but also resulted in a significant change in the membrane permeability of E. coli. Unexpectedly, the removal of the mcr-1 gene increased cell viability under high osmotic stress conditions (e.g., 7.0% NaCl) and led to increased resistance to hydrophobic antibiotics. Increased expression of mcr-1 also resulted in decreased growth rate and changed the cellular morphology of E. coli. Collectively, our results revealed that the spread of mcr-1-carrying plasmids alters other physiological functions in addition to conferring colistin resistance. |
| first_indexed | 2024-12-21T09:30:05Z |
| format | Article |
| id | doaj.art-f3a952f1bda94649935512e675c7c85f |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-21T09:30:05Z |
| publishDate | 2020-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-f3a952f1bda94649935512e675c7c85f2022-12-21T19:08:46ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2020-01-011010.3389/fmicb.2019.03015499109Colistin Resistance Gene mcr-1 Mediates Cell Permeability and Resistance to Hydrophobic AntibioticsBaiyuan Li0Fang Yin1Xuanyu Zhao2Xuanyu Zhao3Yunxue Guo4Weiquan Wang5Weiquan Wang6Pengxia Wang7Honghui Zhu8Yeshi Yin9Xiaoxue Wang10Xiaoxue Wang11Key Laboratory of Comprehensive Utilization of Advantage Plants Resources in Hunan South, College of Chemistry and Bioengineering, Hunan University of Science and Engineering, Yongzhou, ChinaDepartment of Breast and Thyroid Surgery, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, ChinaKey Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, ChinaUniversity of the Chinese Academy of Sciences, Beijing, ChinaKey Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, ChinaKey Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, ChinaUniversity of the Chinese Academy of Sciences, Beijing, ChinaKey Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, ChinaState Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Open Laboratory of Applied Microbiology, Guangdong Microbial Culture Collection Center, Guangdong Institute of Microbiology, Guangzhou, ChinaKey Laboratory of Comprehensive Utilization of Advantage Plants Resources in Hunan South, College of Chemistry and Bioengineering, Hunan University of Science and Engineering, Yongzhou, ChinaKey Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, ChinaUniversity of the Chinese Academy of Sciences, Beijing, ChinaColistin is considered the last-resort antibiotic used to treat multidrug resistant bacteria-related infections. However, the discovery of the plasmid-mediated colistin resistance gene, mcr-1, threatens the clinical utility of colistin antibiotics. In this study, the physiological function of MCR-1, which encodes an LPS-modifying enzyme, was investigated in E. coli K-12. Specifically, the impact of mcr-1 on membrane permeability and antibiotic resistance of E. coli was assessed by constructing an mcr-1 deletion mutant and by a complementation study. The removal of the mcr-1 gene from plasmid pHNSHP45 not only led to reduced resistance to colistin but also resulted in a significant change in the membrane permeability of E. coli. Unexpectedly, the removal of the mcr-1 gene increased cell viability under high osmotic stress conditions (e.g., 7.0% NaCl) and led to increased resistance to hydrophobic antibiotics. Increased expression of mcr-1 also resulted in decreased growth rate and changed the cellular morphology of E. coli. Collectively, our results revealed that the spread of mcr-1-carrying plasmids alters other physiological functions in addition to conferring colistin resistance.https://www.frontiersin.org/article/10.3389/fmicb.2019.03015/fullmcr-1colistin resistancepermeabilityhydrophobic antibioticsplasmid |
| spellingShingle | Baiyuan Li Fang Yin Xuanyu Zhao Xuanyu Zhao Yunxue Guo Weiquan Wang Weiquan Wang Pengxia Wang Honghui Zhu Yeshi Yin Xiaoxue Wang Xiaoxue Wang Colistin Resistance Gene mcr-1 Mediates Cell Permeability and Resistance to Hydrophobic Antibiotics Frontiers in Microbiology mcr-1 colistin resistance permeability hydrophobic antibiotics plasmid |
| title | Colistin Resistance Gene mcr-1 Mediates Cell Permeability and Resistance to Hydrophobic Antibiotics |
| title_full | Colistin Resistance Gene mcr-1 Mediates Cell Permeability and Resistance to Hydrophobic Antibiotics |
| title_fullStr | Colistin Resistance Gene mcr-1 Mediates Cell Permeability and Resistance to Hydrophobic Antibiotics |
| title_full_unstemmed | Colistin Resistance Gene mcr-1 Mediates Cell Permeability and Resistance to Hydrophobic Antibiotics |
| title_short | Colistin Resistance Gene mcr-1 Mediates Cell Permeability and Resistance to Hydrophobic Antibiotics |
| title_sort | colistin resistance gene mcr 1 mediates cell permeability and resistance to hydrophobic antibiotics |
| topic | mcr-1 colistin resistance permeability hydrophobic antibiotics plasmid |
| url | https://www.frontiersin.org/article/10.3389/fmicb.2019.03015/full |
| work_keys_str_mv | AT baiyuanli colistinresistancegenemcr1mediatescellpermeabilityandresistancetohydrophobicantibiotics AT fangyin colistinresistancegenemcr1mediatescellpermeabilityandresistancetohydrophobicantibiotics AT xuanyuzhao colistinresistancegenemcr1mediatescellpermeabilityandresistancetohydrophobicantibiotics AT xuanyuzhao colistinresistancegenemcr1mediatescellpermeabilityandresistancetohydrophobicantibiotics AT yunxueguo colistinresistancegenemcr1mediatescellpermeabilityandresistancetohydrophobicantibiotics AT weiquanwang colistinresistancegenemcr1mediatescellpermeabilityandresistancetohydrophobicantibiotics AT weiquanwang colistinresistancegenemcr1mediatescellpermeabilityandresistancetohydrophobicantibiotics AT pengxiawang colistinresistancegenemcr1mediatescellpermeabilityandresistancetohydrophobicantibiotics AT honghuizhu colistinresistancegenemcr1mediatescellpermeabilityandresistancetohydrophobicantibiotics AT yeshiyin colistinresistancegenemcr1mediatescellpermeabilityandresistancetohydrophobicantibiotics AT xiaoxuewang colistinresistancegenemcr1mediatescellpermeabilityandresistancetohydrophobicantibiotics AT xiaoxuewang colistinresistancegenemcr1mediatescellpermeabilityandresistancetohydrophobicantibiotics |