Molecular epidemiology of isolates with multiple mcr plasmids from a pig farm in Great Britain: the effects of colistin withdrawal in the short and long term

J Antimicrob Chemother. 2018 Nov 1;73(11):3025-3033. doi: 10.1093/jac/dky292.

Abstract

Background: The environment, including farms, might act as a reservoir for mobile colistin resistance (mcr) genes, which has led to calls for reduction of usage in livestock of colistin, an antibiotic of last resort for humans.

Objectives: To establish the molecular epidemiology of mcr Enterobacteriaceae from faeces of two cohorts of pigs, where one group had initially been treated with colistin and the other not, over a 5 month period following stoppage of colistin usage on a farm in Great Britain; faecal samples were also taken at ∼20 months.

Methods: mcr-1 Enterobacteriaceae were isolated from positive faeces and was WGS performed; conjugation was performed on selected Escherichia coli and colistin MICs were determined.

Results: E. coli of diverse ST harbouring mcr-1 and multiple resistance genes were isolated over 5 months from both cohorts. Two STs, from treated cohorts, contained both mcr-1 and mcr-3 plasmids, with some isolates also harbouring multiple copies of mcr-1 on different plasmids. The mcr-1 plasmids grouped into four Inc types (X4, pO111, I2 and HI2), with mcr-3 found in IncP. Multiple copies of mcr plasmids did not have a noticeable effect on colistin MIC, but they could be transferred simultaneously to a Salmonella host in vitro. Neither mcr-1 nor mcr-3 was detected in samples collected ∼20 months after colistin cessation.

Conclusions: We report for the first known time on the presence in Great Britain of mcr-3 from MDR Enterobacteriaceae, which might concurrently harbour multiple copies of mcr-1 on different plasmids. However, control measures, including stoppage of colistin, can successfully mitigate long-term on-farm persistence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / pharmacology
  • Colistin / administration & dosage*
  • Colistin / pharmacology
  • DNA, Bacterial / genetics
  • Drug Resistance, Multiple, Bacterial / genetics*
  • Enterobacteriaceae / drug effects*
  • Enterobacteriaceae / genetics
  • Enterobacteriaceae / isolation & purification
  • Enterobacteriaceae Infections / epidemiology
  • Enterobacteriaceae Infections / veterinary*
  • Escherichia coli Proteins / genetics
  • Farms
  • Feces / microbiology
  • Livestock / microbiology
  • Microbial Sensitivity Tests
  • Plasmids / genetics*
  • Swine
  • Time Factors
  • Transferases (Other Substituted Phosphate Groups) / genetics
  • United Kingdom / epidemiology
  • Whole Genome Sequencing

Substances

  • Anti-Bacterial Agents
  • DNA, Bacterial
  • Escherichia coli Proteins
  • MCR-1 protein, E coli
  • MCR-3 protein, E coli
  • Transferases (Other Substituted Phosphate Groups)
  • Colistin