Diversified mcr-1-Harbouring Plasmid Reservoirs Confer Resistance to Colistin in Human Gut Microbiota

Huiyan Ye; Yihui Li; Zhencui Li; Rongsui Gao; Han Zhang; Ronghui Wen; George F Gao; Qinghua Hu; Youjun Feng

doi:10.1128/mBio.00177-16

Diversified mcr-1-Harbouring Plasmid Reservoirs Confer Resistance to Colistin in Human Gut Microbiota

mBio. 2016 Apr 5;7(2):e00177. doi: 10.1128/mBio.00177-16.

Authors

Huiyan Ye¹, Yihui Li², Zhencui Li³, Rongsui Gao³, Han Zhang³, Ronghui Wen⁴, George F Gao⁵, Qinghua Hu⁶, Youjun Feng⁷

Affiliations

¹ Department of Medical Microbiology and Parasitology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China College of Life Science and Technology, Guangxi University, Nanning City, Guangxi, China.
² Department of Medical Microbiology and Parasitology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China Shenzhen Centre for Disease Control and Prevention, Shenzhen City, Guangdong, China.
³ Department of Medical Microbiology and Parasitology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
⁴ College of Life Science and Technology, Guangxi University, Nanning City, Guangxi, China.
⁵ CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
⁶ Shenzhen Centre for Disease Control and Prevention, Shenzhen City, Guangdong, China.
⁷ Department of Medical Microbiology and Parasitology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China fengyj@zju.edu.cn.

Abstract

Colistin is an ultimate line of refuge against multidrug-resistant Gram-negative pathogens. Very recently, the emergence of plasmid-mediatedmcr-1colistin resistance has become a great challenge to global public health, raising the possibility that dissemination of themcr-1gene is underestimated and diversified. Here, we report three cases of plasmid-carried MCR-1 colistin resistance in isolates from gut microbiota of diarrhea patients. Structural and functional analyses determined that the colistin resistance is conferred purely by the singlemcr-1gene. Genetic and sequence mapping revealed thatmcr-1-harbouring plasmid reservoirs are present in diversity. Together, the data represent the first evidence of diversity inmcr-1-harbouring plasmid reservoirs of human gut microbiota.

Importance: The plasmid-mediated mobile colistin resistance gene (mcr-1) challenged greatly the conventional idea mentioned above that colistin is an ultimate line of refuge against lethal infections by multidrug-resistant Gram-negative pathogens. It is a possibility that diversified dissemination of themcr-1gene might be greatly underestimated. We report three cases of plasmid-carried MCR-1 colistin resistance in isolates from gut microbiota of diarrhea patients and functionally define the colistin resistance conferred purely by the singlemcr-1gene. Genetic and sequence mapping revealed unexpected diversity among themcr-1-harbouring plasmid reservoirs of human gut microbiota.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / pharmacology*
Bacterial Infections / microbiology
China
Colistin / pharmacology*
Diarrhea / microbiology
Drug Resistance, Bacterial*
Ethanolaminephosphotransferase / genetics*
Feces / microbiology
Gastrointestinal Microbiome / drug effects*
Genes, Bacterial
Genetic Variation
Gram-Negative Bacteria / drug effects*
Gram-Negative Bacteria / isolation & purification
Humans
Plasmids*
Sequence Analysis, DNA

Substances

Anti-Bacterial Agents
Ethanolaminephosphotransferase
Colistin

Grants and funding

This work was funded by National Natural Science Foundation of China (NSFC) (31570027) and Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholars (LR15H190001).