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
JournalLancet Infectious Diseases
Volume16
Issue number2
Early online date19 Nov 2015
DOIs
Publication statusPublished - 1 Feb 2016

Keywords

  • Animals
  • China
  • Colistin
  • Drug Resistance, Bacterial
  • Enterobacteriaceae
  • Enterobacteriaceae Infections
  • Humans
  • Meat
  • Mice
  • Plasmids
  • Polymyxins
  • Swine
  • Swine Diseases

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  • Cite this

    Liu, Y-Y., Wang, Y., Walsh, T. R., Yi, L-X., Zhang, R., Spencer, J., Doi, Y., Tian, G., Dong, B., Huang, X., Yu, L-F., Gu, D., Ren, H., Chen, X., Lv, L., He, D., Zhou, H., Liang, Z., Liu, J-H., & 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. Lancet Infectious Diseases, 16(2), 161-168. https://doi.org/10.1016/S1473-3099(15)00424-7