Group 2 and 3 ABC-transporter-dependent capsular K-loci contribute significantly to variation in the estimated invasive potential of Escherichia coli

The major opportunistic pathogen Escherichia coli is the largest cause of antimicrobial resistance (AMR) associated infections and deaths globally. Considerable antigenic diversity has been documented in Extra-intestinal pathogenic E. coli (ExPEC), however, phenotypic capsular (K) typing has fallen out of use. We assembled and curated an in silico capsular locus typing database for group 2 and group 3 K-loci from >20,000 genomes and applied it to carriage and disease cohorts to investigate capsule epidemiology and evolution. Several widely circulating K-loci have estimated odds ratios of >7 for being found in bloodstream infections compared with carriage. The relative invasive potential differed between lineages, and notably, even between subclades of the multidrug-resistant ST131 clone. Our investigation highlights several capsules and lineages that contribute disproportionately to invasive ExPEC disease, some of which are also associated with high levels of AMR. These results have generated new insights into capsule epidemiology and evolution and have significant translational potential, including improved ExPEC diagnostics, personalised therapy options, and the ability to build predictive regional risk maps by combining genomic surveys with demographic and patient frailty data.