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

Johnning, Anna; Karami, Nahid; Tång Hallbäck, Erika; Müller, Vilhelm; Nyberg, Lena; Buongermino Pereira, Mariana; Stewart, Callum; Ambjörnsson, Tobias LU ; Westerlund, Fredrik and Adlerberth, Ingegerd, et al. (2018) In Microbial Genomics 4(11).
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... (More)

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.

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carbapenem resistance, genotype–phenotype association, human pathogens, whole-genome sequencing
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Microbial Genomics
volume
4
issue
11
publisher
Microbiology Society
external identifiers
  • scopus:85057558677
DOI
10.1099/mgen.0.000233
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English
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yes
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97eab286-1f93-4660-b055-49edeb6216ed
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2018-12-21 10:08:09
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2019-07-16 04:02:27
@article{97eab286-1f93-4660-b055-49edeb6216ed,
  abstract     = {<p>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.</p>},
  author       = {Johnning, Anna and Karami, Nahid and Tång Hallbäck, Erika and Müller, Vilhelm and Nyberg, Lena and Buongermino Pereira, Mariana and Stewart, Callum and Ambjörnsson, Tobias and Westerlund, Fredrik and Adlerberth, Ingegerd and Kristiansson, Erik},
  keyword      = {carbapenem resistance,genotype–phenotype association,human pathogens,whole-genome sequencing},
  language     = {eng},
  number       = {11},
  publisher    = {Microbiology Society},
  series       = {Microbial Genomics},
  title        = {The resistomes of six carbapenem-resistant pathogens - a critical genotype-phenotype analysis},
  url          = {http://dx.doi.org/10.1099/mgen.0.000233},
  volume       = {4},
  year         = {2018},
}