The resistomes of six carbapenem-resistant pathogens - a critical genotype-phenotype analysis
Artikel i vetenskaplig tidskrift, 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.

genotype–phenotype association

carbapenem resistance

human pathogens

whole-genome sequencing

Författare

Anna Johnning

Chalmers, Matematiska vetenskaper, Tillämpad matematik och statistik

Göteborgs universitet

N. Karami

Sahlgrenska akademin

Göteborgs universitet

Erika Tång Hallbäck

Sahlgrenska akademin

Vilhelm Müller

Chalmers, Biologi och bioteknik, Kemisk biologi

Lena Nyberg

Chalmers, Biologi och bioteknik, Kemisk biologi

Mariana Buongermino Pereira

Göteborgs universitet

Chalmers, Matematiska vetenskaper, Tillämpad matematik och statistik

Callum L. Stewart

Lunds universitet

Tobias Ambjörnsson

Lunds universitet

Fredrik Westerlund

Chalmers, Biologi och bioteknik, Kemisk biologi

Ingegerd Adlerberth

Sahlgrenska akademin

Göteborgs universitet

Erik Kristiansson

Chalmers, Matematiska vetenskaper, Tillämpad matematik och statistik

Göteborgs universitet

Microbial Genomics

2057-5858 (eISSN)

Vol. 4 11

Ämneskategorier

Infektionsmedicin

Mikrobiologi

Mikrobiologi inom det medicinska området

DOI

10.1099/mgen.0.000233

PubMed

30461373

Mer information

Senast uppdaterat

2019-03-19