Genomic Epidemiology of Complex, Multispecies, Plasmid-Borne Carbapenemase in in the United Kingdom from 2009 to 2014.

Carbapenem resistance in is a public health threat. carbapenemase (encoded by alleles of the family) is one of the most common transmissible carbapenem resistance mechanisms worldwide. The dissemination of historically has been associated with distinct lineages (clonal group 258 [CG258]), a particular plasmid family (pKpQIL), and a composite transposon (Tn). In the United Kingdom, has represented a large-scale, persistent management challenge for some hospitals, particularly in North West England. The dissemination of 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 -positive isolates (Illumina) and long-read assembly (PacBio)/polishing (Illumina) of 21 isolates for characterization. We observed the dissemination of (predominantly ; 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, 584/604 [97%] isolates; predominantly with ATTGA-ATTGA target site duplications, 465/604 [77%] isolates), 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- and plasmids and the common presence of multiple replicons within plasmid structures (>60%). The substantial genomic plasticity observed has important implications for our understanding of the epidemiology of transmissible carbapenem resistance in for the implementation of adequate surveillance approaches and for control.