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 nontumor regions, respectively. All the recovered clb(+) isolates belonged to the phylogenetic group B2 and were the most predominant type in tumor regions. Hemolytic (a-hemolysin-positive, hlyA(+)) and nonhemolytic (alpha-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 nontumor regions (3/19, 15.8%). Moreover, a significantly higher production of N-myristoyl-D-as+paragine, a by-product of colibactin biosynthesis, was observed in hlyA(+) clb(+) isolates than in hlyA(-) clb(+) isolates. Our results suggest that hlyA(+) clb(+) E. colt 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.