The bacterial genetic determinants of Escherichia coli capacity to cause bloodstream infections in humans - Université Paris-Est-Créteil-Val-de-Marne Access content directly
Journal Articles PLoS Genetics Year : 2023

The bacterial genetic determinants of Escherichia coli capacity to cause bloodstream infections in humans

Judit Burgaya
  • Function : Author
Julie Marin
Guilhem Royer
Bénédicte Condamine
  • Function : Author
Benoit Gachet
  • Function : Author
Olivier Clermont
  • Function : Author
Françoise Jaureguy
  • Function : Author
Charles Burdet
  • Function : Author
Agnès Lefort
  • Function : Author
Victoire de Lastours
Erick Denamur
Marco Galardini
François Blanquart
  • Function : Author

Abstract

Escherichia coli is both a highly prevalent commensal and a major opportunistic pathogen causing bloodstream infections (BSI). A systematic analysis characterizing the genomic determinants of extra-intestinal pathogenic vs. commensal isolates in human populations, which could inform mechanisms of pathogenesis, diagnostic, prevention and treatment is still lacking. We used a collection of 912 BSI and 370 commensal E . coli isolates collected in France over a 17-year period (2000–2017). We compared their pangenomes, genetic backgrounds (phylogroups, STs, O groups), presence of virulence-associated genes (VAGs) and antimicrobial resistance genes, finding significant differences in all comparisons between commensal and BSI isolates. A machine learning linear model trained on all the genetic variants derived from the pangenome and controlling for population structure reveals similar differences in VAGs, discovers new variants associated with pathogenicity (capacity to cause BSI), and accurately classifies BSI vs. commensal strains. Pathogenicity is a highly heritable trait, with up to 69% of the variance explained by bacterial genetic variants. Lastly, complementing our commensal collection with an older collection from 1980, we predict that pathogenicity continuously increased through 1980, 2000, to 2010. Together our findings imply that E . coli exhibit substantial genetic variation contributing to the transition between commensalism and pathogenicity and that this species evolved towards higher pathogenicity.

Dates and versions

hal-04305277 , version 1 (24-11-2023)

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Judit Burgaya, Julie Marin, Guilhem Royer, Bénédicte Condamine, Benoit Gachet, et al.. The bacterial genetic determinants of Escherichia coli capacity to cause bloodstream infections in humans. PLoS Genetics, 2023, 19 (8), pp.e1010842. ⟨10.1371/journal.pgen.1010842⟩. ⟨hal-04305277⟩
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