Genomic epidemiology of a complex, multi-species plasmid-borne bla KPC carbapenemase outbreak in Enterobacterales in the UK, 2009-2014
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Le résumé fourni par la source
ABSTRACT Carbapenem resistance in Enterobacterales is a public health threat. Klebsiella pneumoniae carbapenemase (encoded by alleles of the bla KPC family) is one of the commonest transmissible carbapenem resistance mechanisms worldwide. The dissemination of bla KPC has historically been associated with distinct K. pneumoniae lineages (clonal group 258 [CG258]), a particular plasmid family (pKpQIL), and a composite transposon (Tn 4401) . In the UK, bla KPC has caused a large-scale, persistent outbreak focused on hospitals in North-West England. This outbreak has evolved to be polyclonal and poly-species, but the genetic mechanisms underpinning this evolution have not been elucidated in detail; this study used short-read whole genome sequencing of 604 bla KPC -positive isolates (Illumina) and long-read assembly (PacBio)/polishing (Illumina) of 21 isolates for characterisation. We observed the dissemination of bla KPC (predominantly bla KPC-2 ; 573/604 [95%] isolates) across eight species and more than 100 known sequence types. Although there was some variation at the transposon level (mostly Tn 4401 a, 584/604 (97%) isolates; predominantly with ATTGA-ATTGA target site duplications, 465/604 [77%] isolates), bla KPC spread appears to have been supported by highly fluid, modular exchange of larger genetic segments amongst plasmid populations dominated by IncFIB (580/604 isolates), IncFII (545/604 isolates) and IncR replicons (252/604 isolates). The subset of reconstructed plasmid sequences also highlighted modular exchange amongst non- bla KPC and bla KPC plasmids, and the common presence of multiple replicons within bla KPC plasmid structures (>60%). The substantial genomic plasticity observed has important implications for our understanding of the epidemiology of transmissible carbapenem resistance in Enterobacterales, for the implementation of adequate surveillance approaches, and for control. IMPORTANCE Antimicrobial resistance is a major threat to the management of infections, and resistance to carbapenems, one of the “last line” antibiotics available for managing drug-resistant infections, is a significant problem. This study used large-scale whole genome sequencing over a five-year period in the UK to highlight the complexity of genetic structures facilitating the spread of an important carbapenem resistance gene ( bla KPC ) amongst a number of bacterial species that cause disease in humans. In contrast to a recent pan-European study from 2012-2013(1), which demonstrated the major role of spread of clonal bla KPC - Klebsiella pneumoniae lineages in continental Europe, our study highlights the substantial plasticity in genetic mechanisms underpinning the dissemination of bla KPC . This genetic flux has important implications for: the surveillance of drug resistance (i.e. making surveillance more difficult); detection of outbreaks and tracking hospital transmission; generalizability of surveillance findings over time and for different regions; and for the implementation and evaluation of control interventions.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé, mais le titre doit être comparé manuellement.
- Titre Crossref
- Genomic epidemiology of a complex, multi-species plasmid-borne <i>bla</i> <sub>KPC</sub> carbapenemase outbreak in Enterobacterales in the UK, 2009-2014
- Date Crossref
- 03/10/2019
- Éditeur
- openRxiv
- Type
- posted-content
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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University of Oxford NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance pays non établi dans la noticeUniversité ou école supérieure
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University of Southampton pays non établi dans la noticeUniversité ou école supérieure
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London School of Hygiene & Tropical Medicine pays non établi dans la noticeUniversité ou école supérieure
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Manchester University NHS Foundation Trust pays non établi dans la noticeÉtablissement de santé
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Icahn School of Medicine at Mount Sinai Icahn Institute and Department of Genetics and Genomic Sciences pays non établi dans la noticeUniversité ou école supérieure
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University of Virginia Health System Clinical Microbiology Laboratory pays non établi dans la noticeÉtablissement de santé
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Oxford BioMedica (United Kingdom) pays non établi dans la noticeEntreprise
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Public Health England pays non établi dans la noticeOrganisme public
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Health Education North West pays non établi dans la noticeÉtablissement de santé
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Faculty of Medicine pays non établi dans la noticeUniversité ou école supérieure
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London School of Hygiene and Tropical Medicine Department of Infectious Disease Epidemiology pays non établi dans la noticeUniversité ou école supérieure
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Antimicrobial Resistance and Healthcare Associated Infections (AMRHAI) Reference Unit pays non établi dans la noticeInstitution
NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance — University of Oxford, University of Southampton et London School of Hygiene & Tropical Medicine, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.