Novel Plasmid-Mediated Colistin Resistance Gene mcr-3 in Escherichia coli

• Published in: mBio Vol. 8; no. 3
• Main Authors: Yin, Wenjuan, Li, Hui, Shen, Yingbo, Liu, Zhihai, Wang, Shaolin, Shen, Zhangqi, Zhang, Rong, Walsh, Timothy R, Shen, Jianzhong, Wang, Yang
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 27-06-2017
• Subjects: Animals; Anti-Bacterial Agents - pharmacology; Colistin - pharmacology; Conjugation, Genetic; Drug Resistance, Bacterial; Escherichia coli - drug effects; Escherichia coli - genetics; Escherichia coli - isolation & purification; Gene Transfer, Horizontal; Genes, Bacterial; Observation; Plasmids - analysis; Sequence Analysis, DNA; Sequence Homology; Swine; colistin resistance; mcr-3; Aeromonas; public health; Enterobacteriaceae
• ISSN: 2161-2129; 2150-7511
• DOI: 10.1128/mBio.00543-17

The mobile colistin resistance gene
has attracted global attention, as it heralds the breach of polymyxins, one of the last-resort antibiotics for the treatment of severe clinical infections caused by multidrug-resistant Gram-negative bacteria. To date, six slightly different variants of
, and a second mobile colistin resistance gene,
, have been reported or annotated in the GenBank database. Here, we characterized a third mobile colistin resistance gene,
The gene coexisted with 18 additional resistance determinants in the 261-kb IncHI2-type plasmid pWJ1 from porcine
showed 45.0% and 47.0% nucleotide sequence identity to
and
, respectively, while the deduced amino acid sequence of MCR-3 showed 99.8 to 100% and 75.6 to 94.8% identity to phosphoethanolamine transferases found in other
species and in 10
species, respectively. pWJ1 was mobilized to an
recipient by conjugation and contained a plasmid backbone similar to those of other
-carrying plasmids, such as pHNSHP45-2 from the original
-harboring
strain. Moreover, a truncated transposon element, Tn
, which was characterized only in
, was located upstream of
in pWJ1. This ΔTn
-
element was also identified in a shotgun genome sequence of a porcine
isolate from Malaysia, a human
isolate from Thailand, and a human
serovar Typhimurium isolate from the United States. These results suggest the likelihood of a wide dissemination of the novel mobile colistin resistance gene
among
and aeromonads; the latter may act as a potential reservoir for
The emergence of the plasmid-mediated colistin resistance gene
has attracted substantial attention worldwide. Here, we examined a colistin-resistant
isolate that was negative for both
and
and discovered a novel mobile colistin resistance gene,
The amino acid sequence of MCR-3 aligned closely with phosphoethanolamine transferases from
and
species originating from both clinical infections and environmental samples collected in 12 countries on four continents. Due to the ubiquitous profile of aeromonads in the environment and the potential transfer of
between
and
species, the wide spread of
may be largely underestimated. As colistin has been and still is widely used in veterinary medicine and used at increasing frequencies in human medicine, the continuous monitoring of mobile colistin resistance determinants in colistin-resistant Gram-negative bacteria is imperative for understanding and tackling the dissemination of
genes in both the agricultural and health care sectors.