Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: A microbiological and molecular biological study

Yi Yun Liu, Yang Wang, Timothy R. Walsh, Ling Xian Yi, Rong Zhang, James Spencer, Yohei Doi, Guobao Tian, Baolei Dong, Xianhui Huang, Lin Feng Yu, Danxia Gu, Hongwei Ren, Xiaojie Chen, Luchao Lv, Dandan He, Hongwei Zhou, Zisen Liang, Jian Hua Liu, Jianzhong Shen

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Abstract

Background: Until now, polymyxin resistance has involved chromosomal mutations but has never been reported via horizontal gene transfer. During a routine surveillance project on antimicrobial resistance in commensal Escherichia coli from food animals in China, a major increase of colistin resistance was observed. When an E coli strain, SHP45, possessing colistin resistance that could be transferred to another strain, was isolated from a pig, we conducted further analysis of possible plasmid-mediated polymyxin resistance. Herein, we report the emergence of the first plasmid-mediated polymyxin resistance mechanism, MCR-1, in Enterobacteriaceae. Methods: The mcr-1 gene in E coli strain SHP45 was identified by whole plasmid sequencing and subcloning. MCR-1 mechanistic studies were done with sequence comparisons, homology modelling, and electrospray ionisation mass spectrometry. The prevalence of mcr-1 was investigated in E coli and Klebsiella pneumoniae strains collected from five provinces between April, 2011, and November, 2014. The ability of MCR-1 to confer polymyxin resistance in vivo was examined in a murine thigh model. Findings: Polymyxin resistance was shown to be singularly due to the plasmid-mediated mcr-1 gene. The plasmid carrying mcr-1 was mobilised to an E coli recipient at a frequency of 10-1 to 10-3 cells per recipient cell by conjugation, and maintained in K pneumoniae and Pseudomonas aeruginosa. In an in-vivo model, production of MCR-1 negated the efficacy of colistin. MCR-1 is a member of the phosphoethanolamine transferase enzyme family, with expression in E coli resulting in the addition of phosphoethanolamine to lipid A. We observed mcr-1 carriage in E coli isolates collected from 78 (15%) of 523 samples of raw meat and 166 (21%) of 804 animals during 2011-14, and 16 (1%) of 1322 samples from inpatients with infection. Interpretation: The emergence of MCR-1 heralds the breach of the last group of antibiotics, polymyxins, by plasmid-mediated resistance. Although currently confined to China, MCR-1 is likely to emulate other global resistance mechanisms such as NDM-1. Our findings emphasise the urgent need for coordinated global action in the fight against pan-drug-resistant Gram-negative bacteria. Funding: Ministry of Science and Technology of China, National Natural Science Foundation of China.

Original languageEnglish
Pages (from-to)161-168
Number of pages8
JournalThe Lancet Infectious Diseases
Volume16
Issue number2
DOIs
Publication statusPublished - 01-02-2016

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Colistin
Polymyxins
China
Plasmids
Escherichia coli
Natural Science Disciplines
Horizontal Gene Transfer
Lipid A
Electrospray Ionization Mass Spectrometry
Klebsiella pneumoniae
Enterobacteriaceae
Sequence Homology
Transferases
Thigh
Gram-Negative Bacteria
Meat
Pseudomonas aeruginosa
Genes
Inpatients
Pneumonia

All Science Journal Classification (ASJC) codes

  • Infectious Diseases

Cite this

Liu, Yi Yun ; Wang, Yang ; Walsh, Timothy R. ; Yi, Ling Xian ; Zhang, Rong ; Spencer, James ; Doi, Yohei ; Tian, Guobao ; Dong, Baolei ; Huang, Xianhui ; Yu, Lin Feng ; Gu, Danxia ; Ren, Hongwei ; Chen, Xiaojie ; Lv, Luchao ; He, Dandan ; Zhou, Hongwei ; Liang, Zisen ; Liu, Jian Hua ; Shen, Jianzhong. / Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China : A microbiological and molecular biological study. In: The Lancet Infectious Diseases. 2016 ; Vol. 16, No. 2. pp. 161-168.
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abstract = "Background: Until now, polymyxin resistance has involved chromosomal mutations but has never been reported via horizontal gene transfer. During a routine surveillance project on antimicrobial resistance in commensal Escherichia coli from food animals in China, a major increase of colistin resistance was observed. When an E coli strain, SHP45, possessing colistin resistance that could be transferred to another strain, was isolated from a pig, we conducted further analysis of possible plasmid-mediated polymyxin resistance. Herein, we report the emergence of the first plasmid-mediated polymyxin resistance mechanism, MCR-1, in Enterobacteriaceae. Methods: The mcr-1 gene in E coli strain SHP45 was identified by whole plasmid sequencing and subcloning. MCR-1 mechanistic studies were done with sequence comparisons, homology modelling, and electrospray ionisation mass spectrometry. The prevalence of mcr-1 was investigated in E coli and Klebsiella pneumoniae strains collected from five provinces between April, 2011, and November, 2014. The ability of MCR-1 to confer polymyxin resistance in vivo was examined in a murine thigh model. Findings: Polymyxin resistance was shown to be singularly due to the plasmid-mediated mcr-1 gene. The plasmid carrying mcr-1 was mobilised to an E coli recipient at a frequency of 10-1 to 10-3 cells per recipient cell by conjugation, and maintained in K pneumoniae and Pseudomonas aeruginosa. In an in-vivo model, production of MCR-1 negated the efficacy of colistin. MCR-1 is a member of the phosphoethanolamine transferase enzyme family, with expression in E coli resulting in the addition of phosphoethanolamine to lipid A. We observed mcr-1 carriage in E coli isolates collected from 78 (15{\%}) of 523 samples of raw meat and 166 (21{\%}) of 804 animals during 2011-14, and 16 (1{\%}) of 1322 samples from inpatients with infection. Interpretation: The emergence of MCR-1 heralds the breach of the last group of antibiotics, polymyxins, by plasmid-mediated resistance. Although currently confined to China, MCR-1 is likely to emulate other global resistance mechanisms such as NDM-1. Our findings emphasise the urgent need for coordinated global action in the fight against pan-drug-resistant Gram-negative bacteria. Funding: Ministry of Science and Technology of China, National Natural Science Foundation of China.",
author = "Liu, {Yi Yun} and Yang Wang and Walsh, {Timothy R.} and Yi, {Ling Xian} and Rong Zhang and James Spencer and Yohei Doi and Guobao Tian and Baolei Dong and Xianhui Huang and Yu, {Lin Feng} and Danxia Gu and Hongwei Ren and Xiaojie Chen and Luchao Lv and Dandan He and Hongwei Zhou and Zisen Liang and Liu, {Jian Hua} and Jianzhong Shen",
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Liu, YY, Wang, Y, Walsh, TR, Yi, LX, Zhang, R, Spencer, J, Doi, Y, Tian, G, Dong, B, Huang, X, Yu, LF, Gu, D, Ren, H, Chen, X, Lv, L, He, D, Zhou, H, Liang, Z, Liu, JH & Shen, J 2016, 'Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: A microbiological and molecular biological study', The Lancet Infectious Diseases, vol. 16, no. 2, pp. 161-168. https://doi.org/10.1016/S1473-3099(15)00424-7

Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China : A microbiological and molecular biological study. / Liu, Yi Yun; Wang, Yang; Walsh, Timothy R.; Yi, Ling Xian; Zhang, Rong; Spencer, James; Doi, Yohei; Tian, Guobao; Dong, Baolei; Huang, Xianhui; Yu, Lin Feng; Gu, Danxia; Ren, Hongwei; Chen, Xiaojie; Lv, Luchao; He, Dandan; Zhou, Hongwei; Liang, Zisen; Liu, Jian Hua; Shen, Jianzhong.

In: The Lancet Infectious Diseases, Vol. 16, No. 2, 01.02.2016, p. 161-168.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China

T2 - A microbiological and molecular biological study

AU - Liu, Yi Yun

AU - Wang, Yang

AU - Walsh, Timothy R.

AU - Yi, Ling Xian

AU - Zhang, Rong

AU - Spencer, James

AU - Doi, Yohei

AU - Tian, Guobao

AU - Dong, Baolei

AU - Huang, Xianhui

AU - Yu, Lin Feng

AU - Gu, Danxia

AU - Ren, Hongwei

AU - Chen, Xiaojie

AU - Lv, Luchao

AU - He, Dandan

AU - Zhou, Hongwei

AU - Liang, Zisen

AU - Liu, Jian Hua

AU - Shen, Jianzhong

PY - 2016/2/1

Y1 - 2016/2/1

N2 - Background: Until now, polymyxin resistance has involved chromosomal mutations but has never been reported via horizontal gene transfer. During a routine surveillance project on antimicrobial resistance in commensal Escherichia coli from food animals in China, a major increase of colistin resistance was observed. When an E coli strain, SHP45, possessing colistin resistance that could be transferred to another strain, was isolated from a pig, we conducted further analysis of possible plasmid-mediated polymyxin resistance. Herein, we report the emergence of the first plasmid-mediated polymyxin resistance mechanism, MCR-1, in Enterobacteriaceae. Methods: The mcr-1 gene in E coli strain SHP45 was identified by whole plasmid sequencing and subcloning. MCR-1 mechanistic studies were done with sequence comparisons, homology modelling, and electrospray ionisation mass spectrometry. The prevalence of mcr-1 was investigated in E coli and Klebsiella pneumoniae strains collected from five provinces between April, 2011, and November, 2014. The ability of MCR-1 to confer polymyxin resistance in vivo was examined in a murine thigh model. Findings: Polymyxin resistance was shown to be singularly due to the plasmid-mediated mcr-1 gene. The plasmid carrying mcr-1 was mobilised to an E coli recipient at a frequency of 10-1 to 10-3 cells per recipient cell by conjugation, and maintained in K pneumoniae and Pseudomonas aeruginosa. In an in-vivo model, production of MCR-1 negated the efficacy of colistin. MCR-1 is a member of the phosphoethanolamine transferase enzyme family, with expression in E coli resulting in the addition of phosphoethanolamine to lipid A. We observed mcr-1 carriage in E coli isolates collected from 78 (15%) of 523 samples of raw meat and 166 (21%) of 804 animals during 2011-14, and 16 (1%) of 1322 samples from inpatients with infection. Interpretation: The emergence of MCR-1 heralds the breach of the last group of antibiotics, polymyxins, by plasmid-mediated resistance. Although currently confined to China, MCR-1 is likely to emulate other global resistance mechanisms such as NDM-1. Our findings emphasise the urgent need for coordinated global action in the fight against pan-drug-resistant Gram-negative bacteria. Funding: Ministry of Science and Technology of China, National Natural Science Foundation of China.

AB - Background: Until now, polymyxin resistance has involved chromosomal mutations but has never been reported via horizontal gene transfer. During a routine surveillance project on antimicrobial resistance in commensal Escherichia coli from food animals in China, a major increase of colistin resistance was observed. When an E coli strain, SHP45, possessing colistin resistance that could be transferred to another strain, was isolated from a pig, we conducted further analysis of possible plasmid-mediated polymyxin resistance. Herein, we report the emergence of the first plasmid-mediated polymyxin resistance mechanism, MCR-1, in Enterobacteriaceae. Methods: The mcr-1 gene in E coli strain SHP45 was identified by whole plasmid sequencing and subcloning. MCR-1 mechanistic studies were done with sequence comparisons, homology modelling, and electrospray ionisation mass spectrometry. The prevalence of mcr-1 was investigated in E coli and Klebsiella pneumoniae strains collected from five provinces between April, 2011, and November, 2014. The ability of MCR-1 to confer polymyxin resistance in vivo was examined in a murine thigh model. Findings: Polymyxin resistance was shown to be singularly due to the plasmid-mediated mcr-1 gene. The plasmid carrying mcr-1 was mobilised to an E coli recipient at a frequency of 10-1 to 10-3 cells per recipient cell by conjugation, and maintained in K pneumoniae and Pseudomonas aeruginosa. In an in-vivo model, production of MCR-1 negated the efficacy of colistin. MCR-1 is a member of the phosphoethanolamine transferase enzyme family, with expression in E coli resulting in the addition of phosphoethanolamine to lipid A. We observed mcr-1 carriage in E coli isolates collected from 78 (15%) of 523 samples of raw meat and 166 (21%) of 804 animals during 2011-14, and 16 (1%) of 1322 samples from inpatients with infection. Interpretation: The emergence of MCR-1 heralds the breach of the last group of antibiotics, polymyxins, by plasmid-mediated resistance. Although currently confined to China, MCR-1 is likely to emulate other global resistance mechanisms such as NDM-1. Our findings emphasise the urgent need for coordinated global action in the fight against pan-drug-resistant Gram-negative bacteria. Funding: Ministry of Science and Technology of China, National Natural Science Foundation of China.

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