Genomic epidemiology of global Klebsiella pneumoniae carbapenemase (KPC)-producing Escherichia coli

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