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ABSTRACT The dissemination of carbapenem resistance in Escherichia coli has major implications for the management of common human infections. bla KPC , encoding a transmissible carbapenemase (KPC), has historically largely been associated with Klebsiella pneumoniae, a predominant plasmid (pKpQIL), and a specific transposable element (Tn 4401, ~10kb). Here we characterize the genetic features of the emergence of bla KPC in global E. coli, 2008-2013, using both long-and short-read whole genome sequencing. Amongst 43/45 successfully sequenced bla KPC - E. coli strains, we identified high strain (n=21 sequence types, 18% of annotated genes in the core genome); plasmid (≥9 replicon types); and bla KPC -associated, mobile genetic element (MGE) diversity (50% not within complete Tn 4401 elements). We also found evidence of interspecies, regional and international plasmid spread. In several cases bla KPC 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 bla KPC with a range of MGEs previously linked to the successful spread of widely endemic resistance mechanisms (e.g. bla T EM , bla CTX-M ) suggests that it is likely to become similarly prevalent.

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