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Face of Tobias Ambjörnsson. Photo.

Tobias Ambjörnsson

Senior lecturer

Face of Tobias Ambjörnsson. Photo.

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

Author

  • Anna Johnning
  • Nahid Karami
  • Erika Tång Hallbäck
  • Vilhelm Müller
  • Lena Nyberg
  • Mariana Buongermino Pereira
  • Callum Stewart
  • Tobias Ambjörnsson
  • Fredrik Westerlund
  • Ingegerd Adlerberth
  • Erik Kristiansson

Summary, in English

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.

Department/s

  • Computational Biology and Biological Physics

Publishing year

2018-11

Language

English

Publication/Series

Microbial Genomics

Volume

4

Issue

11

Document type

Journal article

Publisher

Microbiology Society

Topic

  • Microbiology

Keywords

  • carbapenem resistance
  • genotype–phenotype association
  • human pathogens
  • whole-genome sequencing

Status

Published

ISBN/ISSN/Other

  • ISSN: 2057-5858