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

Journal article
Authors Anna Johnning
Nahid Karami
Erika Tång Hallbäck
V. Muller
L. Nyberg
Mariana Buongermino Pereira
C. Stewart
T. Ambjornsson
F. Westerlund
Ingegerd Adlerberth
Erik Kristiansson
Published in Microbial Genomics
Volume 4
Issue 11
ISSN 2057-5858
Publication year 2018
Published at Department of Mathematical Sciences
Centre for antibiotic resistance research, CARe
Institute of Biomedicine, Department of Infectious Medicine
Language en
Keywords whole-genome sequencing, carbapenem resistance, genotype-phenotype association, human, metallo-beta-lactamase, complete nucleotide-sequence, pseudomonas-aeruginosa, antibiotic-resistance, escherichia-coli, antimicrobial resistance, klebsiella-pneumoniae, topoisomerase-iv, quinolone-resistance, bacterial-resistance
Subject categories Microbiology in the medical area


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 colt, 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: bla(KPC-2), bla(OXA-48), bla(OXA-72), bla(NDM-1), bla(NDm-7) and bla(VIM-1). In addition, a novel version of bla(SHv) 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 colocalized on these and other plasmids, suggesting a risk for coselection. 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.

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