Cross-species convergence of surface polysaccharides shapes the virulence of an atypical carbapenem resistant uropathogenic Escherichia coli clone

Abstract Carbapenem-resistant Escherichia coli (CREC) is an emerging global health threat associated with limited treatment options and increased mortality. Here, analysis of 20,331 E. coli genomes from urinary tract infection (UTI) and urine samples identifies phylogroup A sequence type 361 (ST361) as an emerging CREC clone associated with UTI. Phylogenetic and phylodynamic analyses reveal two dominant ST361 clades that emerged in Asia around 2006 and subsequently disseminated intercontinentally. ST361 exhibits near pan-drug resistance, with bla NDM-5 conferring carbapenem resistance. In silico capsule and O-antigen typing reveals a highly conserved Klebsiella -like surface polysaccharide serotype in 95.9% of ST361 genomes, which we show contributes to virulence in UTI and catheter-associated UTI mouse models. Analysis of the mobile genetic elements harbouring bla NDM-5 in ST361 and other CREC further reveals a dynamic interplay between plasmid transfer and insertion elements that contributes to bla NDM-5 dissemination. Together, these findings identify ST361 as an emerging UTI-associated CREC clone and reveal the convergence of clonal expansion, virulence-associated surface architecture and mobile genetic elements in its spread.