Induction of DNA Damage in Mouse Colorectum by Administration of Colibactin-producing Escherichia coli, Isolated from a Patient With Colorectal Cancer

Abstract

Background/aim: Among colorectal cancer-associated intestinal microbiota, colibactin-producing (clb⁺) bacteria are attracting attention. We aimed to clarify the interaction between clb⁺ Escherichia coli and normal colorectal epithelial cells in vivo and in vitro.

Materials and methods: Five-week-old female Balb/c mice were divided in an untreated group, a group treated with clb⁺ E. coli isolated from a Japanese patient with colorectal cancer (E. coli-50), and a group treated with non colibactin-producing E. coli (E. coli-50/ΔclbP). Mice were sacrificed at 18 weeks of treatment.

Results: Treatment with clb⁺ E. coli increased positivity for H2A histone family member X phosphorylated at Ser-139 (γH2AX) in epithelial cells of the luminal surface of the mouse rectum but this did not occur in the E. coli-50/ΔclbP and untreated groups. In an in vitro setting, the ratio of apoptotic cells was increased and cell counts were reduced by treatment with clb⁺ E. coli more than in untreated cells and normal rat colorectal epithelial cells.

Conclusion: E. coli-50 induced DNA damage in the mouse rectum, possibly by direct interaction between clb⁺ E. coli and normal colorectal epithelial cells. Our findings imply that regulation of clb⁺ E. coli infection may be a useful strategy for colorectal cancer control.

Keywords: Colibactin; DNA damage; colorectal cancer; mouse; γH2AX-positive cells.