Abstract
BackgroundThe 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.MethodsIn this study, we sequenced 3468 unselected isolates over a decade in Oxfordshire (UK) and linked this data to routinely collected electronic healthcare records and mandatory surveillance reports. We annotated genomes for clinically relevant genes, contrasting the distribution of these within and between species, and compared incidence trends over time using stacked negative binomial regression.ResultsWe demonstrate that the observed increases in E. coli incidence were not driven by the success of one or more sequence types (STs); instead, four 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).ConclusionsOur 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 (e.g. AMR/virulence genes/sequence type) 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.
Highlights
The incidence of Gram-negative bloodstream infections (BSIs), predominantly caused by Escherichia coli and Klebsiella species, continues to increase; the causes of this are unclear and effective interventions are hard to design
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 (e.g. antimicrobial resistance (AMR)/virulence genes/sequence type) 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 mobile genetic elements (MGEs) to try and understand horizontal gene transfer networks
Escherichia coli bloodstream infections are stably dominated by major lineages across community and healthcare-associated settings, but with diverse sporadic lineages accounting for almost half of cases, and evidence of sub-lineage replacement in major sequence types (STs) From September 2008 to December 2018, 3461 E. coli isolates from 3196 patients were sequenced
Summary
The incidence of Gram-negative bloodstream infections (BSIs), predominantly caused by Escherichia coli and Klebsiella species, continues to increase; the causes of this are unclear and effective interventions are hard to design. Gram-negative bloodstream infections (GNBSI), predominantly caused by Escherichia coli and Klebsiella spp., are a significant and increasing threat to public health. They are the leading cause of bloodstream infection (BSI) in the UK with a substantial associated burden of morbidity and mortality [1, 2]. Whilst infections caused by relatively susceptible isolates still represent the majority of cases, the potential for rapid proliferation of AMRassociated clones and the dissemination of AMR genes on mobile genetic elements between lineages and species is a major concern [9]
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