Published online Jun 7, 2014. doi: 10.3748/wjg.v20.i21.6560
Revised: February 10, 2014
Accepted: March 8, 2014
Published online: June 7, 2014
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 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.
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.
Core tip: Tumors and mucosa of patients with colon cancer are abnormally colonized by Escherichia coli (E. coli) belonging to B2 phylogroup. The aim of the present study was to provide further insight into the characterization of colon cancer-associated E. coli. Despite their poor ability to adhere to and to invade intestinal epithelial cells in vitro, we showed that colon cancer-associated E. coli induce carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) expression, a receptor involved in adhesion of pathogenic E. coli. These bacteria were also able to persist and promote low grade inflammation and cell proliferation, in a chronic infection model of CEACAM6 expressing mice, highlighting their oncogenic potential.