Genomes of Escherichia coli bacteraemia isolates originating from urinary tract foci contain more virulence-associated genes than those from non-urinary foci and neutropaenic hosts

J Infect. 2018 Dec;77(6):534-543. doi: 10.1016/j.jinf.2018.10.011. Epub 2018 Nov 2.

Abstract

Objectives: Escherichia coli is the leading cause of bacteraemia. In an era of emerging multi-drug-resistant strains, development of effective preventative strategies will be informed by knowledge of strain diversity associated with specific infective syndromes/patient groups. We hypothesised that the number of virulence factor (VF) genes amongst bacteraemia isolates from neutropaenic patients would be lower than isolates from immunocompetent patients.

Methods: Immunocompetent and neutropaenic adults with E. coli bacteraemia were recruited prospectively and the source of bacteraemia determined. VF gene profiles were established in silico following whole genome sequencing.

Results: Isolates from individual patients were monoclonal. Strains from immunocompetent patients with urinary tract infective foci (UTIF) harboured more VF genes (median number of VF genes 16, range 8-24) than isolates from both immunocompetent patients with non-UTIF (10, 2-22, p = 0.0058) and neutropaenic patients with unknown focus of infection (NPUFI) (8, 3-13, p < 0.0001). Number of VF genes (OR 1.21, 95% CIs 1.01-1.46, p = 0.039) and urinary catheter/recurrent urinary tract infection (OR 12.82, 95% CIs 1.24-132.65, p = 0.032) were independent predictors of bacteraemia secondary to UTIF vs. non-UTIF in immunocompetent patients. papA, papC, papE/F, papG, agn43, tia, iut, fyuA, kpsM and sat were significantly more prevalent amongst UTIF- vs non-UTIF-originating isolates amongst immunocompetent patients, while papC, papE/F, papG, agn43, tia, fyuA, hlyA, usp and clb were significantly more prevalent amongst UTIF- vs NPUFI-associated isolates.

Conclusions: Bacteraemia-associated E. coli strains originating from UTIF have distinct VF gene profiles from strains associated with non-UTIF- and NPUFI. This diversity must be addressed in the design of future vaccines to ensure adequate coverage of strains responsible for site-specific disease.

Keywords: Antimicrobial resistance; Bacteraemia; Escherichia coli; ExPEC; Neutropaenia; Virulence factor; Whole genome sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bacteremia / microbiology
  • Escherichia coli / genetics*
  • Escherichia coli / isolation & purification
  • Escherichia coli / pathogenicity
  • Escherichia coli Infections / blood
  • Escherichia coli Infections / urine*
  • Female
  • Genome, Bacterial*
  • Humans
  • Immunocompetence
  • Male
  • Middle Aged
  • Neutropenia / microbiology
  • Phylogeny
  • Prospective Studies
  • Sequence Analysis, DNA
  • United Kingdom
  • Urinary Tract Infections / microbiology*
  • Virulence
  • Virulence Factors / genetics*
  • Whole Genome Sequencing
  • Young Adult

Substances

  • Virulence Factors