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

• Published in: Japanese Journal of Infectious Diseases Vol. 73; no. 6; pp. 437 - 442
• Main Authors: Yoshikawa, Yuko, Tsunematsu, Yuta, Matsuzaki, Nobuo, Hirayama, Yuichiro, Higashiguchi, Fumi, Sato, Michio, Iwashita, Yuji, Miyoshi, Noriyuki, Mutoh, Michihiro, Ishikawa, Hideki, Sugimura, Haruhiko, Wakabayashi, Keiji, Watanabe, Kenji
• Format: Journal Article
• Language: English
• Published: National Institute of Infectious Diseases, Japanese Journal of Infectious Diseases Editorial Committee 30.11.2020
• Subjects: colibactin; colorectal cancer; commensal Escherichia coli; hemolytic activity
• ISSN: 1344-6304; 1884-2836
• DOI: 10.7883/yoken.JJID.2020.066

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.