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CEA CHRU CNRS CPU INR A INRI A INSER M INSTITUT PASTEUR IR D 1 CEA CHRU CNRS CPU INR A INRI A INSER M INSTITUT PASTEUR IR D Escherichia coli : the enemy within Eric Oswald UMR 1043 - INSERM - CNRS – Univ Toulouse III USC INRA CHU Toulouse-ENVT
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Page 1: 1.5 eric oswald

CEA CHRU

CNRS

CPU INRA

INRIA INSERM

INSTITUT PASTEUR

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1CEA CHRU

CNRS

CPU INRA

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Escherichia coli : the enemy within

Eric Oswald

UMR 1043 - INSERM - CNRS – Univ Toulouse IIIUSC INRA

CHU Toulouse-ENVT

Eric Oswald
visuelle de TOULOUSECarte de Francevisuelle bât
Eric Oswald
visuelle de TOULOUSECarte de Francevisuelle bât
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E. coli is the predominant facultative anaerobe in the gut

Escherichia coli are commensal bacteria of the gastrointestinal

tract of healthy humans and animals

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E. coli belongs to the initial microflora colonizing the gut of newborns

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E. coli is also a highly versatile bacterial species with considerable pathogenic potential

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E. coli O104:H4 Outbreak

Caused by Sprouts?

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

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Croxen & Finlay, 2010, Nat Rev Microbiol

High number of very different pathotypes E. coli due to genome

plasticity

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Only 40% of the genome of E. coli (the 'core' genome) is highly conserved between strains

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An emerging hybrid E. coli pathotype

+

EAEC

= EHEC O104:H4

Stx2EaggEC Virulence plasmid

Colonization of the gut

Toxin productionHemolytic-

uremic syndrome

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R1 NH

O

OH

HN

OOH

O

NH

OHN

OSH

O

N

S HN

OCONH2

O

COOR2

Colibactin in silico predicted struture

This gene cluster encodes a complex polyketide-nonribosomal peptide hybrids compound : Colibactin

pks cluster: 52 kb

5,1 Mb DNA

pks : a pathogenicity island present in the genome of E. coli responsable of sepsis and urinary tract infections

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Nougayrede et al Science 2006

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Colibactin induces double-strand breaks in host DNA

Colibactin is a virulence factor But…

Colibactin exacerbates lymphopenia during sepsis

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Pks-island

…present in ExPEC and commensal E. coli

Distribution of the pks-island among E. colipopulation

E. coli phylogenetic group B2 strains have increased in proportion among commensal intestinal E. coli in Western countries in the last decades.

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E. coli pks+

g-H2AXMutant clbAIR 2 Gy

Control

Colon loop assay

Commensal E. coli pks+ induces DNA double strand breaks in

colonocytes in vivoDNA double strand breaks can give rise to genomic instability and may induce or promote cancer

Chromatid break

Chromosomal aberrationsCuevas et al PNAS 2010

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A link between colorectal cancer and commensal E. coli producing

colibactin ?

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« commensal » E. coli can be also very bad guy…

Breaking the Barrier Between Commensalism and Pathogenicity

I am not a cucumber

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Perspectives

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Get started in life with the good E. coli…

Understand the « commensal » life of opportunistic pathogen

Virulence factors (genes and products) as targets for new anti-infective drugs

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Thank you for your attention