The resistomes of six carbapenem-resistant pathogens - a critical genotype-phenotype analysis
Journal article, 2018

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.

human pathogens

whole-genome sequencing

genotype–phenotype association

carbapenem resistance

Author

Anna Johnning

University of Gothenburg

Chalmers, Mathematical Sciences, Applied Mathematics and Statistics

N. Karami

University of Gothenburg

Erika Tång Hallbäck

University of Gothenburg

Vilhelm Müller

Chalmers, Biology and Biological Engineering, Chemical Biology

Lena Nyberg

Chalmers, Biology and Biological Engineering, Chemical Biology

Mariana Buongermino Pereira

University of Gothenburg

Chalmers, Mathematical Sciences, Applied Mathematics and Statistics

Callum L. Stewart

Lund University

Tobias Ambjörnsson

Lund University

Fredrik Westerlund

Chalmers, Biology and Biological Engineering, Chemical Biology

Ingegerd Adlerberth

University of Gothenburg

Erik Kristiansson

University of Gothenburg

Chalmers, Mathematical Sciences, Applied Mathematics and Statistics

Microbial Genomics

2057-5858 (eISSN)

Vol. 4 11

Subject Categories

Infectious Medicine

Microbiology

Microbiology in the medical area

DOI

10.1099/mgen.0.000233

PubMed

30461373

More information

Latest update

11/22/2019