Characterization of commensal colibactin-producing Escherichia coli isolated from colorectal cancer patients

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K08841
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Bacteriology (including mycology)
• Research Institution: Nippon Veterinary and Life Science University
• Principal Investigator: Yoshikawa Yuko 日本獣医生命科学大学, 獣医学部, 講師 (00580523)
• Co-Investigator(Kenkyū-buntansha): 三好 規之 静岡県立大学, 食品栄養科学部, 准教授 (70438191)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: コリバクチン / 大腸菌 / 腸内細菌

Outline of Final Research Achievements

Colibactin is a genotoxin produced by a part of Escherichia coli is often isolated as an intestinal commensal. In this study, to clarify the relationship between commensal E. coli and colibactin production in Japanese colorectal adenocarcinoma, we investigated 729 E. coli strains isolated from tumor and its surrounding non-tumor regions of 34 Japanese colorectal adenocarcinoma patients. A total of 450 clb genes-positive (clb+) strains were isolated from 11 patients. The prevalence of clb+ strains in tumor regions was significantly higher than that in non-tumor regions. In addition, we demonstrated that hemolytic (hemolysin+) clb+ strains were dominant in tumor regions, and these bacteria accelerated the production of N-myristoyl-D-asparagine (N-myr-Asn), a by-product of colibactin biosynthesis. These results suggested that E. coli, equipped with both hemolysin and colibactin, possess an advantage in colorectal colonization and subsequent carcinogenesis.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

ここ数年、大腸がんの罹患率は部位別の上位を占め、さらに他のがんと比較すると増加が著しい。腫瘍部位におけるコリバクチン産生菌の優占化および大腸がんや炎症性腸疾患の患者におけるコリバクチン産生菌の高い検出率から、大腸におけるコリバクチンの産生増加が、大腸がんの発生に関連するリスクファクターの1つであることが推測される。それゆえ、本研究の成果はコリバクチン産生菌の大腸粘膜上皮への局所的な集積を防ぐ腸内環境の是正方法やコリバクチン産生の制御法の開発へとつながり、さらにはコリバクチンを精度の高い大腸がんのリスクマーカーとして確立できれば、優れたがんの一次予防戦略と成り得る。