Genome wide association study of Escherichia coli bloodstream infection isolates identifies genetic determinants for the portal of entry but not fatal outcome

PLoS Genet. 2022 Mar 24;18(3):e1010112. doi: 10.1371/journal.pgen.1010112. eCollection 2022 Mar.

Abstract

Escherichia coli is an important cause of bloodstream infections (BSI), which is of concern given its high mortality and increasing worldwide prevalence. Finding bacterial genetic variants that might contribute to patient death is of interest to better understand infection progression and implement diagnostic methods that specifically look for those factors. E. coli samples isolated from patients with BSI are an ideal dataset to systematically search for those variants, as long as the influence of host factors such as comorbidities are taken into account. Here we performed a genome-wide association study (GWAS) using data from 912 patients with E. coli BSI from hospitals in Paris, France. We looked for associations between bacterial genetic variants and three patient outcomes (death at 28 days, septic shock and admission to intensive care unit), as well as two portals of entry (urinary and digestive tract), using various clinical variables from each patient to account for host factors. We did not find any association between genetic variants and patient outcomes, potentially confirming the strong influence of host factors in influencing the course of BSI; we however found a strong association between the papGII operon and entrance of E. coli through the urinary tract, which demonstrates the power of bacterial GWAS when applied to actual clinical data. Despite the lack of associations between E. coli genetic variants and patient outcomes, we estimate that increasing the sample size by one order of magnitude could lead to the discovery of some putative causal variants. Given the wide adoption of bacterial genome sequencing of clinical isolates, such sample sizes may be soon available.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacteremia* / epidemiology
  • Bacteremia* / genetics
  • Bacteremia* / microbiology
  • Bacteria
  • Escherichia coli / genetics
  • Escherichia coli Infections* / genetics
  • Escherichia coli Infections* / microbiology
  • Genome-Wide Association Study
  • Humans
  • Sepsis*

Grants and funding

This work was partially funded by a Translational Research Grant from the "Agence Nationale de la Recherche" (ANR, https://anr.fr), Ministry of Higher Education and Research, France 2015 (grant n°ANR-15-CE-17-0019-01). ED was partially supported by the "Fondation pour la Recherche Médicale" (Equipe FRM 2016, grant number DEQ20161136698, https://www.frm.org/). GR was supported by a "Poste d’accueil" funded by the "Assistance Publique-Hôpitaux de Paris" (AP-HP,https://www.aphp.fr/) and the "Commissariat à l'énergie atomique et aux énergies alternatives" (CEA, https://www.cea.fr/) personal grant for his PhD. MG was supported by the "Deutsche Forschungsgemeinschaft" (DFG, German Research Foundation, https://www.dfg.de/) under Germany's Excellence Strategy - EXC 2155 - project number 390874280. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.