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1.5 eric oswald 1.5 eric oswald Presentation Transcript

  • 1
    Escherichia coli : the enemy within
    Eric Oswald
    UMR 1043 - INSERM - CNRS – Univ Toulouse III
    USC INRA
    CHU Toulouse-ENVT
  • Escherichia coli are commensal bacteria of the gastrointestinal tract of healthy humans and animals
    E. coliis the predominant facultative anaerobe in the gut
    2
    E. coli belongs to the initial microflora colonizing the gut of newborns
  • E. coli is also a highly versatile bacterial species with considerable pathogenic potential
    3
    E. coli is a leading cause for infant acute diarrhea and the primary cause of travelers' diarrhea.
    About 10 to 20 percent of women have had at least one episode of urinary tract infection due to E. coli in their lifetime.
    E. coli causes 10-50% of nosocomial infections.
    E. coli is an emerging foodborne pathogen
    E. coli O104:H4 Outbreak Caused by Sprouts?
  • High number of very different pathotypes E. coli due to genome plasticity
    Croxen & Finlay, 2010, Nat Rev Microbiol
    4
    Only 40% of the genome of E. coli (the 'core' genome) is highly conserved between strains
  • An emerging hybrid E. coli pathotype
    +
    =
    EHEC O104:H4
    EaggEC Virulence plasmid
    Stx2
    EAEC
    Hemolytic-uremic syndrome
    Colonization of the gut
    Toxin production
  • 5,1 Mb
    DNA
    This gene cluster encodes a complex polyketide-nonribosomal peptide hybrids compound : Colibactin
    Colibactin in silico predicted struture
    pks : a pathogenicity island present in the genome of E. coli responsable of sepsis and urinary tract infections
    pks cluster: 52 kb
    Nougayrede et al Science 2006
    6
  • Colibactin induces double-strand breaks in host DNA
     Colibactin exacerbates lymphopenia during sepsis
    But…
     Colibactin is a virulence factor
    7
  • Distribution of the pks-island among E. coli
    population
    E. coli phylogenetic group B2 strains have increased in proportion among commensal intestinal E. coli in Western countries in the last decades.
    Pks-island
    …present in ExPEC and commensal E. coli
    8
  • Chromatid break
    Chromosomal aberrations
    Control
    E. coli pks+
    g-H2AX
    IR 2 Gy
    Mutant clbA
    Commensal E. coli pks+ induces DNA double strand breaks in colonocytes in vivo
    DNA double strand breaks can give rise to genomic instability and may induce or promote cancer
    Colon loop assay
    Cuevas et al PNAS 2010
  • A link between colorectal cancer and commensal E. coli producing colibactin ?
    10
  • Breaking the Barrier Between Commensalism and Pathogenicity
    I am not a
    cucumber
    « commensal » E. coli can be also very bad guy…
  • Perspectives
    12
    Virulence factors (genes and products) as targets for new anti-infective drugs
    Understand the « commensal » life of opportunistic pathogen
    Get started in life with the good E. coli…
  • Thank you for your attention