title: Colon cancer-associated B2 Escherichia coli colonize gut mucosa and promote cell proliferation.
abstract: OBJECTIVE
  To provide further insight into the characterization of mucosa-associated Escherichia coli (E. coli) isolated from the colonic mucosa of cancer patients.
  
  
  METHODS
  Phylogroups and the presence of cyclomodulin-encoding genes of mucosa-associated E. coli from colon cancer and diverticulosis specimens were determined by PCR. Adhesion and invasion experiments were performed with I-407 intestinal epithelial cells using gentamicin protection assay. Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) expression in T84 intestinal epithelial cells was measured by enzyme-linked immunosorbent assay and by Western Blot. Gut colonization, inflammation and pro-carcinogenic potential were assessed in a chronic infection model using CEABAC10 transgenic mice. Cell proliferation was analyzed by real-time mRNA quantification of PCNA and immunohistochemistry staining of Ki67.
  
  
  RESULTS
  Analysis of mucosa-associated E. coli from colon cancer and diverticulosis specimens showed that whatever the origin of the E. coli strains, 86% of cyclomodulin-positive E. coli belonged to B2 phylogroup and most harbored polyketide synthase (pks) island, which encodes colibactin, and/or cytotoxic necrotizing factor (cnf) genes. In vitro assays using I-407 intestinal epithelial cells revealed that mucosa-associated B2 E. coli strains were poorly adherent and invasive. However, mucosa-associated B2 E. coli similarly to Crohn's disease-associated E. coli are able to induce CEACAM6 expression in T84 intestinal epithelial cells. In addition, in vivo experiments using a chronic infection model of CEACAM6 expressing mice showed that B2 E. coli strain 11G5 isolated from colon cancer is able to highly persist in the gut, and to induce colon inflammation, epithelial damages and cell proliferation.
  
  
  CONCLUSIONS
  In conclusion, these data bring new insights into the ability of E. coli isolated from patients with colon cancer to establish persistent colonization, exacerbate inflammation and trigger carcinogenesis.
authors.affiliation: Jennifer Raisch, Emmanuel Buc, Mathilde Bonnet, Pierre Sauvanet, Emilie Vazeille, Amélie de Vallée, Denis Pezet, Richard Bonnet, Marie-Agnès Bringer, Arlette Darfeuille-Michaud, Clermont Université, UMR1071 Inserm/Université d'Auvergne and INRA USC2018, 63000 Clermont-Ferrand, France.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Raisch
authors.affiliation: Jennifer Raisch, Emmanuel Buc, Mathilde Bonnet, Pierre Sauvanet, Emilie Vazeille, Amélie de Vallée, Denis Pezet, Richard Bonnet, Marie-Agnès Bringer, Arlette Darfeuille-Michaud, Clermont Université, UMR1071 Inserm/Université d'Auvergne and INRA USC2018, 63000 Clermont-Ferrand, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Buc
authors.affiliation: Jennifer Raisch, Emmanuel Buc, Mathilde Bonnet, Pierre Sauvanet, Emilie Vazeille, Amélie de Vallée, Denis Pezet, Richard Bonnet, Marie-Agnès Bringer, Arlette Darfeuille-Michaud, Clermont Université, UMR1071 Inserm/Université d'Auvergne and INRA USC2018, 63000 Clermont-Ferrand, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Bonnet
authors.affiliation: Jennifer Raisch, Emmanuel Buc, Mathilde Bonnet, Pierre Sauvanet, Emilie Vazeille, Amélie de Vallée, Denis Pezet, Richard Bonnet, Marie-Agnès Bringer, Arlette Darfeuille-Michaud, Clermont Université, UMR1071 Inserm/Université d'Auvergne and INRA USC2018, 63000 Clermont-Ferrand, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Sauvanet
authors.affiliation: Jennifer Raisch, Emmanuel Buc, Mathilde Bonnet, Pierre Sauvanet, Emilie Vazeille, Amélie de Vallée, Denis Pezet, Richard Bonnet, Marie-Agnès Bringer, Arlette Darfeuille-Michaud, Clermont Université, UMR1071 Inserm/Université d'Auvergne and INRA USC2018, 63000 Clermont-Ferrand, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Vazeille
authors.affiliation: Jennifer Raisch, Emmanuel Buc, Mathilde Bonnet, Pierre Sauvanet, Emilie Vazeille, Amélie de Vallée, Denis Pezet, Richard Bonnet, Marie-Agnès Bringer, Arlette Darfeuille-Michaud, Clermont Université, UMR1071 Inserm/Université d'Auvergne and INRA USC2018, 63000 Clermont-Ferrand, France.
authors.forename: Amélie
authors.initials: A
authors.lastname: de Vallée
authors.affiliation: Jennifer Raisch, Emmanuel Buc, Mathilde Bonnet, Pierre Sauvanet, Emilie Vazeille, Amélie de Vallée, Denis Pezet, Richard Bonnet, Marie-Agnès Bringer, Arlette Darfeuille-Michaud, Clermont Université, UMR1071 Inserm/Université d'Auvergne and INRA USC2018, 63000 Clermont-Ferrand, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Déchelotte
authors.affiliation: Jennifer Raisch, Emmanuel Buc, Mathilde Bonnet, Pierre Sauvanet, Emilie Vazeille, Amélie de Vallée, Denis Pezet, Richard Bonnet, Marie-Agnès Bringer, Arlette Darfeuille-Michaud, Clermont Université, UMR1071 Inserm/Université d'Auvergne and INRA USC2018, 63000 Clermont-Ferrand, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Darcha
authors.affiliation: Jennifer Raisch, Emmanuel Buc, Mathilde Bonnet, Pierre Sauvanet, Emilie Vazeille, Amélie de Vallée, Denis Pezet, Richard Bonnet, Marie-Agnès Bringer, Arlette Darfeuille-Michaud, Clermont Université, UMR1071 Inserm/Université d'Auvergne and INRA USC2018, 63000 Clermont-Ferrand, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Pezet
authors.affiliation: Jennifer Raisch, Emmanuel Buc, Mathilde Bonnet, Pierre Sauvanet, Emilie Vazeille, Amélie de Vallée, Denis Pezet, Richard Bonnet, Marie-Agnès Bringer, Arlette Darfeuille-Michaud, Clermont Université, UMR1071 Inserm/Université d'Auvergne and INRA USC2018, 63000 Clermont-Ferrand, France.
authors.forename: Richard
authors.initials: R
authors.lastname: Bonnet
authors.affiliation: Jennifer Raisch, Emmanuel Buc, Mathilde Bonnet, Pierre Sauvanet, Emilie Vazeille, Amélie de Vallée, Denis Pezet, Richard Bonnet, Marie-Agnès Bringer, Arlette Darfeuille-Michaud, Clermont Université, UMR1071 Inserm/Université d'Auvergne and INRA USC2018, 63000 Clermont-Ferrand, France.
authors.forename: Marie-Agnès
authors.initials: MA
authors.lastname: Bringer
authors.affiliation: Jennifer Raisch, Emmanuel Buc, Mathilde Bonnet, Pierre Sauvanet, Emilie Vazeille, Amélie de Vallée, Denis Pezet, Richard Bonnet, Marie-Agnès Bringer, Arlette Darfeuille-Michaud, Clermont Université, UMR1071 Inserm/Université d'Auvergne and INRA USC2018, 63000 Clermont-Ferrand, France.
authors.forename: Arlette
authors.initials: A
authors.lastname: Darfeuille-Michaud
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D018441:Biofilms; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000382:microbiology*; D004240:Diverticulum / Q000382:microbiology; D004926:Escherichia coli / Q000472:pathogenicity*; D005260:Female; D058851:GPI-Linked Proteins / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D007413:Intestinal Mucosa / Q000382:microbiology*; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C504117:CEACAM6 protein, human; C470556:Ceacam10 protein, mouse; D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; D019394:Ki-67 Antigen; D018809:Proliferating Cell Nuclear Antigen
keywords: B2 Escherichia coli; Carcinoembryonic antigen-related cell adhesion molecule 6; Cell proliferation; Colon cancer; Polyketide synthase genomic island