High prevalence of mucosa-associated E. coli producing cyclomodulin and genotoxin in colon cancer

PLoS One. 2013;8(2):e56964. doi: 10.1371/journal.pone.0056964. Epub 2013 Feb 14.


Some Escherichia coli strains produce toxins designated cyclomodulins (CMs) which interfere with the eukaryotic cell cycle of host cells, suggesting a possible link between these bacteria and cancers. There are relatively few data available concerning the colonization of colon tumors by cyclomodulin- and genotoxic-producing E. coli. We did a qualitative and phylogenetic analysis of mucosa-associated E. coli harboring cyclomodulin-encoding genes from 38 patients with colorectal cancer (CRC) and 31 with diverticulosis. The functionality of these genes was investigated on cell cultures and the genotoxic activity of strains devoid of known CM-encoding gene was investigated. Results showed a higher prevalence of B2 phylogroup E. coli harboring the colibatin-producing genes in biopsies of patients with CRC (55.3%) than in those of patients with diverticulosis (19.3%), (p<0.01). Likewise, a higher prevalence of B2 E. coli harboring the CNF1-encoding genes in biopsies of patients with CRC (39.5%) than in those of patients with diverticulosis (12.9%), (p = 0.01). Functional analysis revealed that the majority of these genes were functional. Analysis of the ability of E. coli to adhere to intestinal epithelial cells Int-407 indicated that highly adherent E. coli strains mostly belonged to A and D phylogroups, whatever the origin of the strains (CRC or diverticulosis), and that most E. coli strains belonging to B2 phylogroup displayed very low levels of adhesion. In addition, 27.6% (n = 21/76) E. coli strains devoid of known cyclomodulin-encoding genes induced DNA damage in vitro, as assessed by the comet assay. In contrast to cyclomodulin-producing E. coli, these strains mainly belonged to A or D E. coli phylogroups, and exhibited a non significant difference in the distribution of CRC and diverticulosis specimens (22% versus 32.5%, p = 0.91). In conclusion, cyclomodulin-producing E. coli belonging mostly to B2 phylogroup colonize the colonic mucosa of patients with CRC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bacterial Adhesion
  • Bacterial Toxins / biosynthesis*
  • Bacterial Toxins / genetics
  • Colonic Neoplasms / microbiology*
  • Colonic Neoplasms / pathology
  • Escherichia coli / genetics
  • Escherichia coli / metabolism*
  • Escherichia coli / physiology
  • Humans
  • Intestinal Mucosa / microbiology*
  • Intestinal Mucosa / pathology
  • Middle Aged
  • Mutagens / metabolism*
  • Phenotype
  • Prevalence


  • Bacterial Toxins
  • Mutagens

Grants and funding

This work was supported by the Ministère Français de l'Education Nationale, de la Recherche et de la Technologie, l'Institut national de la santé et de la recherche médicale (Inserm U1071), l'Institut National de la Recherche Agronomique (USC-2018) and la Ligue contre le cancer. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.