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Chromosomal Integration of the Klebsiella pneumoniae carbapenemase gene (blaKPC) in Klebsiella Species: Elusive but not Rare

Mathers, A; Stoesser, N; Chai, W; Carroll, J; Barry, K; Cheruvanky, A; Sebra, R; ... Sheppard, A; + view all (2017) Chromosomal Integration of the Klebsiella pneumoniae carbapenemase gene (blaKPC) in Klebsiella Species: Elusive but not Rare. Antimicrobial Agents and Chemotherapy , 61 (3) , Article e01823-16. 10.1128/AAC.01823-16. Green open access

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Abstract

Carbapenemase genes in Enterobacteriaceae are mostly described as being plasmid-associated. However, the genetic context of carbapenemase genes is not always confirmed in epidemiological surveys, and the frequency of their chromosomal integration is therefore unknown. A previously sequenced collection of blaKPC-positive Enterobacteriaceae from a single US institution (2007 2012; n=281 isolates, 182 patients) was analyzed to identify chromosomal insertions of Tn4401, the transposon most frequently harboring blaKPC. Using a combination of short- and long-read sequencing, we confirmed five independent chromosomal integration events from 6/182 (3%) patients, corresponding to 15/281 (5%) isolates. Three patients had isolates identified by peri-rectal screening and three had infections which were all successfully treated. When a single copy of blaKPC was in the chromosome one or both of the phenotypic carbapenemase tests were negative. All chromosomally integrated blaKPC were from Klebsiella spp., predominantly K. pneumoniae clonal group (CG)258, even though these represented only a small proportion of the isolates. Integration occurred via IS15-ΔI mediated transposition of a larger, composite region encompassing Tn4401 at one locus of chromosomal integration, seen in the same strain (K. pneumoniae ST340) in two patients. In summary, we identified five independent chromosomal integrations of blaKPC in a large outbreak, demonstrating that this is not a rare event. blaKPC was more frequently integrated into the chromosome of epidemic CG258 K. pneumoniae lineages (ST11, ST258, ST340), and was more difficult to detect by routine phenotypic methods in this context. The presence of chromosomally integrated blaKPC within successful, globally disseminated K. pneumoniae strains is therefore likely underestimated.

Type: Article
Title: Chromosomal Integration of the Klebsiella pneumoniae carbapenemase gene (blaKPC) in Klebsiella Species: Elusive but not Rare
Open access status: An open access version is available from UCL Discovery
DOI: 10.1128/AAC.01823-16
Publisher version: http://dx.doi.org/10.1128/AAC.01823-16
Language: English
Additional information: Copyright © 2017 Mathers et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
Keywords: carbapenemase, KPC, Klebsiella, Klebsiella pneumoniae carbapenemase, antibiotic resistance, chromosomal, plasmid analysis, plasmids, transposons, whole-genome sequencing
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL
URI: https://discovery.ucl.ac.uk/id/eprint/1532009
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