title: Interactions between microsatellite instability and human gut colonization byEscherichia coliin colorectal cancer.
abstract: Recent studies suggest that colonization of colonic mucosa by pathogenicEscherichia colicould be involved in the development of colorectal cancer (CRC), especially through the production of genotoxins such as colibactin and/or by interfering with the DNA mismatch repair (MMR) pathway that leads to microsatellite instability (MSI). The present study, performed on 88 CRC patients, revealed a significant increase inE. colicolonization in the MSI CRC phenotype. In the same way,E. colipersistence and internalization were increasedin vitroin MMR-deficient cells. Moreover, we demonstrated that colibactin-producingE. coliinduce inhibition of the mutL homologue 1 (MLH1) MMR proteins, which could lead to genomic instability. However, colibactin-producingE. coliwere more frequently identified in microsatellite stable (MSS) CRC. The present study suggests differences in the involvement of colibactin-producingE. coliin colorectal carcinogenesis according to the CRC phenotype. Further host-pathogen interactions studies should take into account CRC phenotypes.
authors.affiliation: UMR 1071 Inserm/Université Clermont Auvergne, 63000 Clermont-Ferrand, France.|INRA USC-2018, 63000 Clermont-Ferrand, France.|Department of Digestive Surgery, CHU Clermont-Ferrand, 63000 Clermont-Ferrand, France.
authors.forename: Johan
authors.initials: J
authors.lastname: Gagnière
authors.affiliation: UMR 1071 Inserm/Université Clermont Auvergne, 63000 Clermont-Ferrand, France.|INRA USC-2018, 63000 Clermont-Ferrand, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Bonnin
authors.affiliation: Department of Pathology, CHU Clermont-Ferrand, 63000 Clermont-Ferrand, France.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Jarrousse
authors.affiliation: UMR 1071 Inserm/Université Clermont Auvergne, 63000 Clermont-Ferrand, France.|INRA USC-2018, 63000 Clermont-Ferrand, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Cardamone
authors.affiliation: UMR 1071 Inserm/Université Clermont Auvergne, 63000 Clermont-Ferrand, France.|INRA USC-2018, 63000 Clermont-Ferrand, France.|Department of Oncogenetic, Centre Jean Perrin, 63000 Clermont-Ferrand, France.
authors.forename: Allison
authors.initials: A
authors.lastname: Agus
authors.affiliation: Department of Oncogenetic, Centre Jean Perrin, 63000 Clermont-Ferrand, France.
authors.forename: Nancy
authors.initials: N
authors.lastname: Uhrhammer
authors.affiliation: UMR 1071 Inserm/Université Clermont Auvergne, 63000 Clermont-Ferrand, France.|INRA USC-2018, 63000 Clermont-Ferrand, France.|Department of Digestive Surgery, CHU Clermont-Ferrand, 63000 Clermont-Ferrand, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Sauvanet
authors.affiliation: Department of Pathology, CHU Clermont-Ferrand, 63000 Clermont-Ferrand, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Déchelotte
authors.affiliation: UMR 1071 Inserm/Université Clermont Auvergne, 63000 Clermont-Ferrand, France.|INRA USC-2018, 63000 Clermont-Ferrand, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Barnich
authors.affiliation: UMR 1071 Inserm/Université Clermont Auvergne, 63000 Clermont-Ferrand, France.|INRA USC-2018, 63000 Clermont-Ferrand, France.|Department of Bacteriology, CHU Clermont-Ferrand, 63000 Clermont-Ferrand, France.
authors.forename: Richard
authors.initials: R
authors.lastname: Bonnet
authors.affiliation: UMR 1071 Inserm/Université Clermont Auvergne, 63000 Clermont-Ferrand, France.|INRA USC-2018, 63000 Clermont-Ferrand, France.|Department of Digestive Surgery, CHU Clermont-Ferrand, 63000 Clermont-Ferrand, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Pezet
authors.affiliation: UMR 1071 Inserm/Université Clermont Auvergne, 63000 Clermont-Ferrand, France mathilde.bonnet@udamail.fr.|INRA USC-2018, 63000 Clermont-Ferrand, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Bonnet
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000382:microbiology* / Q000601:surgery; D053843:DNA Mismatch Repair / Q000235:genetics; D045643:DNA Repair Enzymes / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics; D004926:Escherichia coli / Q000302:isolation & purification* / Q000378:metabolism; D005260:Female; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D007413:Intestinal Mucosa / Q000382:microbiology; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D061065:Polyketides / Q000378:metabolism; D011446:Prospective Studies
chemical_list: D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D010455:Peptides; D061065:Polyketides; C569566:colibactin; D045643:DNA Repair Enzymes
keywords: Escherichia coli; colibactin; colorectal cancer; microsatellite instability; mutL homologue 1 (MLH1); oxidative stress