Colon cancer-associated B2 Escherichia coli colonize gut mucosa and promote cell proliferation

• Published in: World journal of gastroenterology : WJG Vol. 20; no. 21; pp. 6560 - 6572
• Main Author: Raisch, Jennifer
• Format: Journal Article
• Language: English
• Published: United States Baishideng Publishing Group Co. Limited 07.06.2014; Baishideng Publishing Group Inc
• Subjects: Adult; Aged; Aged, 80 and over; Animals; antigen-relat; Antigens, CD - metabolism; Biofilms; Carcinoembryonic; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; Cell Proliferation; coli; Colonic Neoplasms - microbiology; Diverticulum - microbiology; Escherichia; Escherichia coli - pathogenicity; Evidence-Based Medicine; Female; GPI-Linked Proteins - metabolism; Human health and pathology; Humans; Hépatology and Gastroenterology; Inflammation; Intestinal Mucosa - microbiology; Ki-67 Antigen - metabolism; Life Sciences; Male; Mice; Mice, Transgenic; Middle Aged; Polymerase Chain Reaction; Proliferating Cell Nuclear Antigen - metabolism; Cell proliferation; Polyketide synthase genomic island; Colon cancer; Carcinoembryonic antigen-related cell adhesion molecule 6; B2 Escherichia coli; Carcinoembryonic anti-gen-related cell adhesion molecule 6; EVIDENCE-BASED MEDICINE
• ISSN: 1007-9327; 2219-2840; 2219-2840
• DOI: 10.3748/wjg.v20.i21.6560

AIM: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 weredetermined 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 procarcinogenic 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 CEACAM6expression in T84 intestinal epithelial cells.In addition,in vivo experiments using a chronic infection model of CEACAM6 expressing mice showed that B2 E.coli strain11G5 isolated from colon cancer is able to highly persist in the gut,and to induce colon inflammation,epithelial damages and cell proliferation.CONCLUSION: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.