The dissemination of carbapenem resistance in Escherichia coli has major implications for the
management of common 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, ~10 kb). Here we characterize the genetic features of blaKPC
emergence 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 substantial strain diversity
(n = 21 sequence types, 18% of annotated genes in the core genome); substantial plasmid diversity (≥9
replicon types); and substantial blaKPC-associated, mobile genetic element (MGE) diversity (50% not
within complete Tn4401 elements). We also found evidence of inter-species, 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 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 may become similarly prevalent.