Abstract
Carbapenem resistance in Enterobacterales is a public health threat. Klebsiella pneumoniae carbapenemase (encoded by alleles of the blaKPC family) is one of the most common transmissible carbapenem resistance mechanisms worldwide. The dissemination of blaKPC historically has been associated with distinct K. pneumoniae lineages (clonal group 258 [CG258]), a particular plasmid family (pKpQIL), and a composite transposon (Tn4401). In the United Kingdom, blaKPC has represented a large-scale, persistent management challenge for some hospitals, particularly in North West England. The dissemination of blaKPC has evolved to be polyclonal and polyspecies, but the genetic mechanisms underpinning this evolution have not been elucidated in detail; this study used short-read whole-genome sequencing of 604 blaKPC-positive isolates (Illumina) and long-read assembly (PacBio)/polishing (Illumina) of 21 isolates for characterization. We observed the dissemination of blaKPC (predominantly blaKPC-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 Tn4401a, 584/604 [97%] isolates; predominantly with ATTGA-ATTGA target site duplications, 465/604 [77%] isolates), blaKPC spread appears to have been supported by highly fluid, modular exchange of larger genetic segments among plasmid populations dominated by IncFIB (580/604 isolates), IncFII (545/604 isolates), and IncR (252/ 604 isolates) replicons. The subset of reconstructed plasmid sequences (21 isolates, 77 plasmids) also highlighted modular exchange among non-blaKPC and blaKPC plasmids and the common presence of multiple replicons within blaKPC 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.
| Original language | English |
|---|---|
| Article number | e02244-19 |
| Journal | Antimicrobial Agents and Chemotherapy |
| Volume | 64 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 1 May 2020 |
Bibliographical note
Funding Information:We are grateful to and acknowledge the sharing of isolates by microbiology and clinical teams from contributing UK hospitals and from Martin Cormican, the National Reference Laboratory in Galway, Ireland, and the contributing laboratories in Ireland. We are also grateful to the microbiology laboratory staff and infection control teams at Manchester University NHS Foundation Trust (formerly CMFT and UHSM); the staff of the Manchester Medical Microbiology Partnership; and the research laboratory, informatics, and project management teams working as part of the Modernizing Medical Microbiology Consortium, Oxford. Contemporaneous investigation by CMFT, UHSM, and PHE was undertaken as part of routine activity. The retrospective investigation was funded by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Healthcare-Associated Infections and Antimicrobial Resistance at Oxford University in partnership with Public Health England (PHE) (grant HPRU-2012-10041) and supported by the NIHR Biomedical Research Centre, Oxford. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research, the Department of Health, or Public Health England. N.S. is funded by a PHE/University of Oxford Academic Clinical Lectureship. T.E.A.P., D.W.C., and A.S.W. are NIHR Senior Investigators. The Transmission of Carbapenemase-Producing Enterobacteriaceae (TRACE) study investigators are listed alphabetically and include several of the authors also listed by name in the main author list: Zoie Aiken, Oluwafemi Akinremi, Aiysha Ali, Julie Caw-thorne, Paul Cleary, Derrick W. Crook, Valerie Decraene, Andrew Dodgson, Michel Doumith, Matthew J. Ellington, Ryan George, John Grimshaw, Malcolm Guiver, Robert Hill, Katie L. Hopkins, Rachel Jones, Cheryl Lenney, Amy J. Mathers, Ashley McEwan, Ginny Moore, Mark Neilson, Sarah Neilson, Timothy E. A. Peto, Hang T. T. Phan, Mark Regan, Anna C. Seale, Nicole Stoesser, Jay Turner-Gardner, Vicky Watts, A. Sarah Walker, Jimmy Walker, David Wyllie, William Welfare, and Neil Woodford. None of the authors has any conflicts of interest to declare.
Funding Information:
Contemporaneous investigation by CMFT, UHSM, and PHE was undertaken as part of routine activity. The retrospective investigation was funded by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Healthcare- Associated Infections and Antimicrobial Resistance at Oxford University in partnership with Public Health England (PHE) (grant HPRU-2012-10041) and supported by the NIHR Biomedical Research Centre, Oxford. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research, the Department of Health, or Public Health England. N.S. is funded by a PHE/University of Oxford Academic Clinical Lectureship. T.E.A.P., D.W.C., and A.S.W. are NIHR Senior Investigators.*%blankline%*
Publisher Copyright:
Copyright © 2020 American Society for Microbiology. All Rights Reserved.
Keywords
- Carbapenemase
- Enterobacterales
- Genomic epidemiology
- KPC
- Long-read sequencing
- Outbreak analysis
- Short-read sequencing
- Whole-genome sequencing
