Characterization of Colibactin-Producing Escherichia coli Isolated from Japanese Patients with Colorectal Cancer.

We investigated the relationship between colibactin-producing (clb ⁺ ) Escherichia coli and colorectal adenocarcinoma. In total, 729 E. coli colonies were isolated from tumor and surrounding non-tumor regions in resected specimens from 34 Japanese patients; 450 colonies were from the tumor regions and 279 from the non-tumor regions. clb ⁺ bacteria were found in tumor regions of 11 patients (11/34, 32.4%) and they were also detected in the non-tumor regions of 7 out of these 11 patients (7/34, 20.6%). The prevalence of clb ⁺ isolates was 72.7% (327/450) and 44.1% (123/279) in tumor and non-tumor regions, respectively. All the recovered clb ⁺ isolates belonged to the phylogenetic group B2 and were the most predominant type in tumor regions. Hemolytic (α-hemolysin-positive, hlyA ⁺ ) and non-hemolytic (α-hemolysin-negative, hlyA ^- ) clb ⁺ isolates were obtained from patient #19; however, the prevalence of hlyA ⁺ clb ⁺ isolates was significantly higher in tumor regions (35/43, 81.4%) than in non-tumor regions (3/19, 15.8%). Moreover, a significantly higher production of N-myristoyl-D-asparagine, a by-product of colibactin biosynthesis, was observed in hlyA ⁺ clb ⁺ isolates than in hlyA ^- clb ⁺ isolates. Our results suggest that hlyA ⁺ clb ⁺ E. coli may have a selective advantage in colorectal colonization and, consequently, might play a role in carcinogenesis. The presence of hlyA ⁺ clb ⁺ bacteria in healthy individuals is a potential risk marker of colorectal cancer.