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

Ruichao Li, Miaomiao Xie, Jinfei Zhang, Zhiqiang Yang, Lizhang Liu, Xiaobo Liu, Zhiwei Zheng, Edward Wai Chi Chan, Sheng Chen

Research output: Journal article publicationJournal articleAcademic researchpeer-review

115 Citations (Scopus)

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 plasmidswere 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.
Original languageEnglish
Pages (from-to)393-401
Number of pages9
JournalJournal of Antimicrobial Chemotherapy
Volume72
Issue number2
DOIs
Publication statusPublished - 1 Jan 2017

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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