The bacterial genetic determinants ofEscherichia colicapacity to cause bloodstream infections in humans

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, diagnostics, prevention and treatment is still lacking. We used a collection of 1282 BSI and commensal E. coli isolates collected in France over a 17-year period (2000-2017) and 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 increased steadily from 23% in 1980 to 46% in 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.

Strain intrinsic properties and environmental constraints together shape Escherichia coli dynamics and diversity over a twenty-year human gut time series

“…We inferred the posterior distribution of the residence time for each observed clone (Table S4). Most of the clones (30) out of 35) were seen only once and consequently had very wide inferred posterior residence times distributions (with a mode at 2.1 days), reflecting the poor information on the true residence times of these clones in our data. Long term intestinal residence of colonizing E. coli has been associated with the presence of specific clones belonging mainly to B2/D/F phylogroups, iron capture systems (17,55), and fluoroquinolone resistance (56).…”

“…We inferred the posterior distribution of the residence time for each observed clone (Table S4). Most of the clones (30) out of 35) were seen only once and consequently had very wide inferred posterior residence times distributions (with a mode at 2.1 days), reflecting the poor information on the true residence times of these clones in our data. The remaining five clones classified as resident have a posterior mode of residence time ranging from 10.1 to 437.1 days.…”

“…Commensal E. coli strains were gathered from stools of 359 healthy adults living in the Paris area or Brittany (both locations in the Northern part of France) between 2000 to 2017. One strain per individual was sequenced as above (30). The 1,777 RefSeq E. coli genomes of high quality were downloaded from NCBI (July 2022).…”