kiny
Well-known member
- Joined
- Apr 28, 2011
- Messages
- 3,463
Full http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0056964
High Prevalence of Mucosa-Associated E. coli Producing Cyclomodulin and Genotoxin in Colon Cancer
Emmanuel Buc equal contributor,Damien Dubois equal contributor,Pierre Sauvanet,Jennifer Raisch,Julien Delmas,Arlette Darfeuille-Michaud equal contributor,Denis Pezet equal contributor,Richard Bonnet equal contributor
Clermont Université, Clermont-Ferrand, France
February 14, 2013
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.
A higher level of colonization with B2 E. coli has also been observed in inflammatory bowel disease (IBD) [44]. In Crohn's disease patients, such colonization was accompanied by increased ileal expression of the glycoprotein CEACAM6, which acts as a receptor for type 1 pili produced by E. coli [45], [46]. Interestingly, Crohn's disease-associated B2 E. coli strains can induce the expression of CEACAM6 in intestinal epithelial cells, and yet CEACAM6 is a human tumor maker, whose overexpression has been observed in colonic tumors [47], [48].
High Prevalence of Mucosa-Associated E. coli Producing Cyclomodulin and Genotoxin in Colon Cancer
Emmanuel Buc equal contributor,Damien Dubois equal contributor,Pierre Sauvanet,Jennifer Raisch,Julien Delmas,Arlette Darfeuille-Michaud equal contributor,Denis Pezet equal contributor,Richard Bonnet equal contributor
Clermont Université, Clermont-Ferrand, France
February 14, 2013
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.
A higher level of colonization with B2 E. coli has also been observed in inflammatory bowel disease (IBD) [44]. In Crohn's disease patients, such colonization was accompanied by increased ileal expression of the glycoprotein CEACAM6, which acts as a receptor for type 1 pili produced by E. coli [45], [46]. Interestingly, Crohn's disease-associated B2 E. coli strains can induce the expression of CEACAM6 in intestinal epithelial cells, and yet CEACAM6 is a human tumor maker, whose overexpression has been observed in colonic tumors [47], [48].
