Open AccessGenomic Epidemiology of Complex, Multispecies, Plasmid-Borne bla KPC Carbapenemase in Enterobacterales in the United Kingdom from 2009 to 2014
Author(s) -
Nicole Stoesser,
Hang Phan,
Anna C. Seale,
Zoie Aiken,
Stéphanie Thomas,
Matthew Smith,
David Wyllie,
Ryan George,
Robert Sebra,
Amy J Mathers,
Alison Vaughan,
Timothy Peto,
Matthew J. Ellington,
Katie L. Hopkins,
Derrick Crook,
Alex Orlek,
William Welfare,
Julie Cawthorne,
Cheryl Lenney,
Andrew Dodgson,
Neil Woodford,
A. Sarah Walker
Publication year - 2020
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.02244-19
Subject(s) - klebsiella pneumoniae , plasmid , biology , transposable element , microbiology and biotechnology , molecular epidemiology , genetics , carbapenem , virology , genotype , gene , genome , escherichia coli , antibiotics
Carbapenem resistance in Enterobacterales is a public health threat. Klebsiella pneumoniae carbapenemase (encoded by alleles of the bla KPC family) is one of the most common transmissible carbapenem resistance mechanisms worldwide. The dissemination of bla KPC historically has been associated with distinct K. pneumoniae lineages (clonal group 258 [CG258]), a particular plasmid family (pKpQIL), and a composite transposon (Tn 4401 ). In the United Kingdom, bla KPC has represented a large-scale, persistent management challenge for some hospitals, particularly in North West England. The dissemination of bla KPC 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 bla KPC -positive isolates (Illumina) and long-read assembly (PacBio)/polishing (Illumina) of 21 isolates for characterization. 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 4401a , 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 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- 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.