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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Escherichia coli : the enemy within
Eric Oswald
UMR 1043 - INSERM - CNRS – Univ Toulouse IIIUSC INRA
CHU Toulouse-ENVT
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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