Ten-year longitudinal molecular epidemiology study of Escherichia coli and Klebsiella species bloodstream infections in Oxfordshire, UK

Samuel Lipworth*, Karina Doris Vihta, Kevin Chau, Leanne Barker, Sophie George, James Kavanagh, Timothy Davies, Alison Vaughan, Monique Andersson, Katie Jeffery, Sarah Oakley, Marcus Morgan, Susan Hopkins, Timothy E.A. Peto, Derrick W. Crook, Ann Sarah Walker, Nicole Stoesser

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: 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. 

Methods: In 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. 

Results: We 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). 

Conclusions: 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. 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.

Original languageEnglish
Article number144
JournalGenome Medicine
Volume13
Issue number1
DOIs
Publication statusPublished - 3 Sep 2021

Bibliographical note

Funding Information:
The research was supported by the National Institute for Health Research (NIHR) Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance (NIHR200915) at the University of Oxford in partnership with Public Health England (PHE) and by Oxford NIHR Biomedical Research Centre. T Peto and AS Walker are NIHR Senior Investigators. The report presents independent research funded by NIHR. The views expressed in this publication are those of the authors and not necessarily those of the NHS, NIHR, the Department of Health or Public Health England. The computational aspects of this research were funded from the NIHR Oxford BRC with additional support from the Wellcome Trust Core Award Grant Number 203141/Z/16/Z. SL is supported by a Medical Research Council Clinical Research Training Fellowship. KC is Medical Research Foundation-funded.

Open Access: s This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Publisher Copyright: © 2021, The Author(s).

Citation: Lipworth, S., Vihta, KD., Chau, K. et al. Ten-year longitudinal molecular epidemiology study of Escherichia coli and Klebsiella species bloodstream infections in Oxfordshire, UK. Genome Med 13, 144 (2021).

DOI: https://doi.org/10.1186/s13073-021-00947-2

Keywords

  • Antimicrobial resistance
  • Bacteraemia
  • Gram-negative bloodstream infections
  • Virulence
  • Whole genome sequencing, Klebsiella pneumoniae

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