Co-occurrence of mcr-1 in the chromosome and on an IncHI2 plasmid: persistence of colistin resistance in Escherichia coli

Int J Antimicrob Agents. 2018 Jun;51(6):842-847. doi: 10.1016/j.ijantimicag.2018.01.007. Epub 2018 Jan 31.

Abstract

Two colistin-resistant Escherichia coli strains (FS13Z2S and FS3Z6C) possessing chromosomally encoded mcr-1 isolated from swine were characterised. Whole-genome sequencing revealed that in strain FS13Z2S mcr-1 occurred in triplicate in the chromosome with another copy encoded on a pHNSHP45-2-like IncHI2 plasmid, whereas in strain FS3Z6C only one copy mcr-1 was inserted in the chromosome. It seems likely that the triplication of chromosomal copies of mcr-1 in FS13Z2S is due to intramolecular transposition events via a composite transposon containing an mcr-1 cassette bracketed by two copies of insertion sequence ISApl1, and the pap2 gene at the insertion site was truncated by an IS1294-like element. In plasmid pFS13Z2S and the chromosome of strain FS3Z6C, only a single copy of ISApl1 was present upstream of the mcr-1 cassette. The two strains exhibited similar colistin minimum inhibitory concentrations (MICs) and featured phosphoethanolamine addition to lipid A, without regard to the copy number of mcr-1. The mcr-1-harbouring plasmid was unstable in wild-type strain FS13Z2S and was quickly lost after 7 days of passage on colistin-free Luria-Bertani broth containing 0.5% SDS, but the mcr-1 copies on the chromosome persisted. These results reveal that the single copy of mcr-1 could result in modification of lipopolysaccharide (LPS) and cause colistin resistance in E. coli. Acquisition of multiple copies of mcr-1, especially on the chromosome, would facilitate stable persistence of colistin resistance in the host strain.

Keywords: Chromosome; Colistin resistance; Escherichia coli; mcr-1.

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Base Sequence
  • Colistin / pharmacology*
  • DNA Transposable Elements / genetics
  • DNA, Bacterial / genetics
  • Drug Resistance, Bacterial / genetics*
  • Escherichia coli / drug effects*
  • Escherichia coli / genetics*
  • Escherichia coli / isolation & purification
  • Escherichia coli Infections / drug therapy
  • Escherichia coli Infections / microbiology
  • Escherichia coli Proteins / genetics*
  • Ethanolamines / chemistry
  • Gene Dosage / genetics
  • Humans
  • Lipid A / chemistry
  • Lipid A / metabolism
  • Microbial Sensitivity Tests
  • Plasmids / genetics
  • Sequence Analysis, DNA

Substances

  • Anti-Bacterial Agents
  • DNA Transposable Elements
  • DNA, Bacterial
  • Escherichia coli Proteins
  • Ethanolamines
  • Lipid A
  • MCR-1 protein, E coli
  • phosphorylethanolamine
  • Colistin