Molecular epidemiology of Escherichia coli and Klebsiella species bloodstream infections in Oxfordshire (UK) 2008-2018

The incidence of Gram-negative bloodstream infections (BSIs), predominantly caused by Escherichia coli and Klebsiella species, continues to increase; however the causes of this are unclear and effective interventions are therefore hard to design. In this study we sequenced 3468 sequential, unselected isolates over a decade in Oxfordshire, UK. We demonstrate that the observed increases in E. coli incidence were not driven by clonal expansion; instead, four major sequence types (STs) continue to dominate a stable population structure, with no evidence of adaptation to hospital/community settings. Conversely in Klebsiella spp. most infections are caused by sporadic STs with the exception of a local drug-resistant outbreak strain (ST490). Virulence elements are highly structured by ST in E. coli but not Klebsiella spp. where they occur in a diverse spectrum of STs and equally across healthcare and community settings. Most clinically hypervirulent (i.e. community-onset) Klebsiella BSIs have no known acquired virulence loci. Finally we demonstrate a diverse but largely genus-restricted mobilome with close associations between antimicrobial resistance (AMR) genes and insertion sequences but not typically specific plasmid replicon types; consistent with the dissemination of AMR genes being highly contingent on smaller mobile genetic elements (MGEs). Our large genomic study highlights distinct differences in the molecular epidemiology of E. coli and Klebsiella BSIs, and suggests that no single specific pathogen genetic factors are likely contributing to the increasing incidence of BSI overall, that association with AMR genes in E. coli is a contributor to the increasing number of E. coli BSIs, and that more attention should be given to AMR gene associations with non-plasmid MGEs to try and understand horizontal gene transfer networks.