Genetic characterization of mcr-1-bearing plasmids to depict molecular mechanisms underlying dissemination of the colistin resistance determinant

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

95 Scopus Citations
View graph of relations

Author(s)

  • Ruichao Li
  • Jinfei Zhang
  • Zhiqiang Yang
  • Lizhang Liu
  • Xiaobo Liu
  • Zhiwei Zheng
  • Edward Wai-Chi Chan

Detail(s)

Original languageEnglish
Pages (from-to)393-401
Journal / PublicationJournal of Antimicrobial Chemotherapy
Volume72
Issue number2
Online published28 Sep 2016
Publication statusPublished - Feb 2017
Externally publishedYes

Abstract

Objectives: To analyse and compare mcr-1-bearing plasmids from animal Escherichia coli isolates, and to investigate potential mechanisms underlying dissemination of mcr-1. Methods: Ninety-seven ESBL-producing E. coli strains isolated from pig farms in China were screened for the mcr-1 gene. Fifteen mcr-1-positive strains were subjected to molecular characterization and bioinformatic analysis of the mcr-1-bearing plasmids that they harboured. Results: Three major types of mcr-1-bearing plasmids were recovered: IncX4 (~33 kb), IncI2 (~60 kb) and IncHI2 (~216-280 kb), among which the IncX4 and IncI2 plasmids were found to harbour the mcr-1 gene only, whereas multiple resistance elements including blaCTX-M, blaCMY, blaTEM, fosA, qnrS, floR and oqxAB were detected, in various combinations, alongside mcr-1 in the IncHI2 plasmids. The profiles of mcr-1-bearing plasmids in the test strains were highly variable, with coexistence of two mcr-1-bearing plasmids being common. However, the MIC of colistin was not affected by the number of mcr-1-carrying plasmids harboured. Comparative analysis of the plasmids showed that they contained an mcr-1 gene cassette with varied structures (mcr-1-orf, ISApl1-mcr-1-orf and Tn6330), with the IncHI2 type being the most active in acquiring foreign resistance genes. A novel transposon, Tn6330, with the structure ISApl1-mcr-1-orf-ISApl1was found to be the key element mediating translocation of mcr-1 into various plasmid backbones through formation of a circular intermediate. Conclusions: The mcr-1 gene can be disseminated via multiple mobile elements including Tn6330, its circular intermediate and plasmids harbouring such elements. It is often co-transmitted with other resistance determinants through IncHI2 plasmids. The functional mechanism of Tn6330, a typical composite transposon harbouring mcr-1, should be further investigated.

Citation Format(s)

Genetic characterization of mcr-1-bearing plasmids to depict molecular mechanisms underlying dissemination of the colistin resistance determinant. / Li, Ruichao; Xie, Miaomiao; Zhang, Jinfei; Yang, Zhiqiang; Liu, Lizhang; Liu, Xiaobo; Zheng, Zhiwei; Chan, Edward Wai-Chi; Chen, Sheng.

In: Journal of Antimicrobial Chemotherapy, Vol. 72, No. 2, 02.2017, p. 393-401.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review