1<br />Escherichia coli : the enemy within<br />Eric Oswald<br />UMR 1043 - INSERM - CNRS – Univ Toulouse III<br />USC INR...
Escherichia coli are commensal bacteria of the gastrointestinal tract of healthy humans and animals<br />E. coliis the pre...
E. coli is also a highly versatile bacterial species with considerable pathogenic potential<br />3<br />E. coli is a leadi...
High number of very different pathotypes E. coli due to genome plasticity<br />Croxen & Finlay, 2010, Nat Rev Microbiol<br...
An emerging hybrid E. coli pathotype<br />+<br />=<br />EHEC O104:H4<br />EaggEC Virulence plasmid<br />Stx2<br />EAEC<br ...
5,1 Mb<br />DNA<br />This gene cluster encodes a complex polyketide-nonribosomal peptide hybrids compound : Colibactin<br ...
Colibactin induces double-strand breaks in host DNA<br /> Colibactin exacerbates lymphopenia during sepsis<br />But…<br /...
Distribution of the pks-island among E. coli<br />population<br />E. coli phylogenetic group B2 strains have increased in ...
Chromatid break<br />Chromosomal aberrations<br />Control<br />E. coli pks+<br />g-H2AX<br />IR 2 Gy<br />Mutant clbA<br /...
A link between colorectal cancer and commensal E. coli producing colibactin ?<br />10<br />
Breaking the Barrier Between Commensalism and Pathogenicity<br />I am not a <br />cucumber<br />« commensal » E. coli can ...
Perspectives<br />12<br />Virulence factors (genes and products) as targets for new anti-infective drugs<br />Understand t...
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1.5 eric oswald

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

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