Escherichia coli (E. coli) are commonly found bacteria that normally live in the intestines of humans and animals. While most E. coli strains are harmless, some can cause illness such as infant diarrhea, urinary tract infections, and foodborne illness. E. coli have a highly plastic genome which allows different pathotypes to emerge, including the deadly E. coli O104:H4 outbreak linked to sprouts. Some commensal E. coli strains produce a toxin called colibactin that can cause DNA damage in host cells and may promote colon cancer. Further research is needed to better understand the factors that allow some E. coli to switch between commensalism and pathogenicity.

1. 1 Escherichia coli : the enemy within Eric Oswald UMR 1043 - INSERM - CNRS – Univ Toulouse III USC INRA CHU Toulouse-ENVT

2. 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

3. 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?

4. 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

5. An emerging hybrid E. coli pathotype + = EHEC O104:H4 EaggEC Virulence plasmid Stx2 EAEC Hemolytic-uremic syndrome Colonization of the gut Toxin production

6. 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

7. Colibactin induces double-strand breaks in host DNA  Colibactin exacerbates lymphopenia during sepsis But…  Colibactin is a virulence factor 7

8. 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

9. 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

10. A link between colorectal cancer and commensal E. coli producing colibactin ? 10

11. Breaking the Barrier Between Commensalism and Pathogenicity I am not a cucumber « commensal » E. coli can be also very bad guy…

12. 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…

13. Thank you for your attention