The resistomes of six carbapenem-resistant pathogens - a critical genotype-phenotype analysis

Research output: Contribution to journalArticle

Abstract

Carbapenem resistance is a rapidly growing threat to our ability to treat refractory bacterial infections. To understand how carbapenem resistance is mobilized and spread between pathogens, it is important to study the genetic context of the underlying resistance mechanisms. In this study, the resistomes of six clinical carbapenem-resistant isolates of five different species - Acinetobacter baumannii, Escherichia coli, two Klebsiella pneumoniae, Proteus mirabilis and Pseudomonas aeruginosa - were characterized using whole genome sequencing. All Enterobacteriaceae isolates and the A. baumannii isolate had acquired a large number of antimicrobial resistance genes (7-18 different genes per isolate), including the following encoding carbapenemases: blaKPC-2, blaOXA-48, blaOXA-72, blaNDM-1, blaNDM-7 and blaVIM-1. In addition, a novel version of blaSHV was discovered. Four new resistance plasmids were identified and their fully assembled sequences were verified using optical DNA mapping. Most of the resistance genes were co-localized on these and other plasmids, suggesting a risk for co-selection. In contrast, five out of six carbapenemase genes were present on plasmids with no or few other resistance genes. The expected level of resistance - based on acquired resistance determinants - was concordant with measured levels in most cases. There were, however, several important discrepancies for four of the six isolates concerning multiple classes of antibiotics. In conclusion, our results further elucidate the diversity of carbapenemases, their mechanisms of horizontal transfer and possible patterns of co-selection. The study also emphasizes the difficulty of using whole genome sequencing for antimicrobial susceptibility testing of pathogens with complex genotypes.

Details

Authors
  • Anna Johnning
  • Nahid Karami
  • Erika Tång Hallbäck
  • Vilhelm Müller
  • Lena Nyberg
  • Mariana Buongermino Pereira
  • Callum Stewart
  • Tobias Ambjörnsson
  • Fredrik Westerlund
  • Ingegerd Adlerberth
  • Erik Kristiansson
Organisations
External organisations
  • University of Gothenburg
  • Chalmers University of Technology
  • Lund University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Microbiology

Keywords

  • carbapenem resistance, genotype–phenotype association, human pathogens, whole-genome sequencing
Original languageEnglish
JournalMicrobial Genomics
Volume4
Issue number11
Publication statusPublished - 2018 Nov
Publication categoryResearch
Peer-reviewedYes