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Title: Genetic characterization of mcr-1-bearing plasmids to depict molecular mechanisms underlying dissemination of the colistin resistance determinant
Authors: Li, RC 
Xie, MM 
Zhang, JF 
Yang, ZQ 
Liu, LZ 
Liu, XB 
Zheng, ZW 
Chan, EWC 
Chen, S 
Issue Date: 2017
Publisher: Oxford University Press
Source: Journal of antimicrobial chemotherapy, 2017, v. 72, no. 2, p. 393-401 How to cite?
Journal: Journal of antimicrobial chemotherapy 
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 (similar to 33 kb), IncI2 (similar to 60 kb) and IncHI2 (similar to 216-280 kb), among which the IncX4 and IncI2 plasmids were found to harbour the mcr-1 gene only, whereas multiple resistance elements including bla(CTX-M), bla(CMY), bla(TEM), 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-mcr1- 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.
ISSN: 0305-7453
EISSN: 1460-2091
DOI: 10.1093/jac/dkw411
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