TY - JOUR T1 - Genomic epidemiology of global <em>Klebsiella pneumoniae</em> carbapenemase (KPC)-producing <em>Escherichia coli</em> JF - bioRxiv DO - 10.1101/111914 SP - 111914 AU - N Stoesser AU - AE Sheppard AU - G Peirano AU - LW Anson AU - L Pankhurst AU - R Sebra AU - HTT Phan AU - A Kasarskis AU - AJ Mathers AU - TEA Peto AU - P Brandford AU - MR Motyl AU - AS Walker AU - DW Crook AU - JD Pitout Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/02/27/111914.abstract N2 - The dissemination of carbapenem resistance in Escherichia coli has major implications for the management of common human infections. blaKPC, encoding a transmissible carbapenemase (KPC), has historically largely been associated with Klebsiella pneumoniae, a predominant plasmid (pKpQIL), and a specific transposable element (Tn4401, ~10kb). Here we characterize the genetic features of the emergence of blaKPC in global E. coli, 2008-2013, using both long-and short-read whole genome sequencing.Amongst 43/45 successfully sequenced blaKPC-E. coli strains, we identified high strain (n=21 sequence types, 18% of annotated genes in the core genome); plasmid (≥9 replicon types); and blaKPC-associated, mobile genetic element (MGE) diversity (50% not within complete Tn4401 elements). We also found evidence of interspecies, regional and international plasmid spread. In several cases blaKPC was found on high copy number, small Col-like plasmids, previously associated with horizontal transmission of resistance genes in the absence of antimicrobial selection pressures.E. coli is a common human pathogen, but also a commensal in a multiple environmental and animal reservoirs, and easily transmissible. The association of blaKPC with a range of MGEs previously linked to the successful spread of widely endemic resistance mechanisms (e.g. blaTEM, blaCTX-M) suggests that it is likely to become similarly prevalent. ER -