Genomic and Molecular Characterization of Clinical Isolates of Enterobacteriaceae Harboring mcr-1 in Colombia, 2002 to 2016

Antimicrob Agents Chemother. 2017 Nov 22;61(12):e00841-17. doi: 10.1128/AAC.00841-17. Print 2017 Dec.

Abstract

Polymyxins are last-resort antimicrobial agents used to treat infections caused by carbapenem-resistant Enterobacteriaceae Due to the worldwide dissemination of polymyxin resistance in animal and human isolates, we aimed to characterize polymyxin resistance associated with the presence of mcr-1 in Enterobacteriaceae and nonfermenter Gram-negative bacilli, using isolates collected retrospectively in Colombia from 2002 to 2016. A total of 5,887 Gram-negative clinical isolates were studied, and 513 were found to be resistant to the polymyxins. Susceptibility to colistin was confirmed by broth microdilution for all mcr-1-positive isolates, and these were further subjected to whole-genome sequencing (WGS). The localization of mcr-1 was confirmed by S1 pulsed-field gel electrophoresis (S1-PFGE) and CeuI-PFGE hybridization. Transferability was evaluated by mating assays. A total of 12 colistin-resistant isolates recovered after 2013 harbored mcr-1, including 8 Escherichia coli, 3 Salmonella enterica serovar Typhimurium, and 1 Klebsiella pneumoniae isolate. E. coli isolates were unrelated by PFGE and belonged to 7 different sequence types (STs) and phylogroups. S Typhimurium and K. pneumoniae isolates belonged to ST34 and ST307, respectively. The mcr-1 gene was plasmid borne in all isolates but two E. coli isolates which harbored it on the chromosome. Conjugation of mcr-1 was successful in 8 of 10 isolates (8.2 × 10-5 to 2.07 × 10-1 cell per recipient). Plasmid sequences showed that the mcr-1 plasmids belonged to four different Inc groups (a new IncP-1 variant and the IncFII, IncHI1, and IncH families). Our results indicate that mcr-1 is circulating in clinical isolates of colistin-resistant Enterobacteriaceae in Colombia and is mainly harbored in transferable plasmids.

Keywords: Colombia; Enterobacteriaceae; genomic; mcr-1.

MeSH terms

  • Anti-Bacterial Agents / therapeutic use*
  • Carbapenems / therapeutic use*
  • Colombia
  • Drug Resistance, Bacterial / genetics*
  • Enterobacteriaceae / drug effects*
  • Enterobacteriaceae / genetics*
  • Enterobacteriaceae / isolation & purification
  • Escherichia coli / drug effects
  • Escherichia coli / genetics
  • Escherichia coli / isolation & purification
  • Escherichia coli Proteins / genetics*
  • Humans
  • Klebsiella pneumoniae / drug effects
  • Klebsiella pneumoniae / genetics
  • Klebsiella pneumoniae / isolation & purification
  • Plasmids / genetics
  • Polymyxins / therapeutic use*
  • Retrospective Studies
  • Salmonella typhimurium / drug effects
  • Salmonella typhimurium / genetics
  • Salmonella typhimurium / isolation & purification

Substances

  • Anti-Bacterial Agents
  • Carbapenems
  • Escherichia coli Proteins
  • MCR-1 protein, E coli
  • Polymyxins