<i>In vitro</i> genotoxicity analyses of colibactin-producing <i>E. coli</i> isolated from a Japanese colorectal cancer patient

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  • Kawanishi Masanobu
    Graduate School of Science and Radiation Research Center, Osaka Prefecture University
  • Hisatomi Yuuta
    Graduate School of Science and Radiation Research Center, Osaka Prefecture University
  • Oda Yoshimitsu
    Graduate School of Science and Radiation Research Center, Osaka Prefecture University
  • Shimohara Chiaki
    Graduate School of Science and Radiation Research Center, Osaka Prefecture University
  • Tsunematsu Yuta
    Department of Pharmaceutical Sciences, University of Shizuoka
  • Sato Michio
    Department of Pharmaceutical Sciences, University of Shizuoka
  • Hirayama Yuichiro
    Department of Pharmaceutical Sciences, University of Shizuoka
  • Miyoshi Noriyuki
    Graduate School of Nutritional and Environmental Sciences, University of Shizuoka
  • Iwashita Yuji
    Department of Tumor Pathology, Hamamatsu University School of Medicine
  • Yoshikawa Yuko
    Graduate School of Nutritional and Environmental Sciences, University of Shizuoka School of Veterinary Medicine, Faculty of Veterinary Science, Nippon Veterinary and Life Science University
  • Sugimura Haruhiko
    Department of Tumor Pathology, Hamamatsu University School of Medicine
  • Mutoh Michihiro
    Division of Prevention, Center for Public Health Sciences, National Cancer Center
  • Ishikawa Hideki
    Department of Molecular-Targeting Cancer Prevention, Kyoto Prefectural University of Medicine
  • Wakabayashi Keiji
    Graduate Division of Nutritional and Environmental Sciences, University of Shizuoka
  • Yagi Takashi
    Graduate School of Science and Radiation Research Center, Osaka Prefecture University
  • Watanabe Kenji
    Department of Pharmaceutical Sciences, University of Shizuoka

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  • In vitro genotoxicity analyses of colibactin-producing E. coli isolated from a Japanese colorectal cancer patient

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Abstract

<p>Colibactin is a polyketide-peptide genotoxin produced by enteric bacteria such as E. coli, and is considered to contribute to the development of colorectal cancer. We previously isolated E. coli strains from Japanese colorectal cancer patients, and in the present study we investigated the genotoxic potency of the colibactin-producing (clb+) E. coli strains that carry the polyketide synthases “pks” gene cluster (pks+) and an isogenic clb- mutant in which the colibactin-producing ability is impaired. Measurement of phosphorylated histone H2AX indicated that DNA double strand breaks were induced in mammalian CHO AA8 cells infected with the clb+ E. coli strains. Induction of DNA damage response (SOS response) by crude extract of the clb+ strains was 1.7 times higher than that of the clb- E. coli in an umu assay with a Salmonella typhimurium TA1535/pSK1002 tester strain. Micronucleus test with CHO AA8 cells revealed that infection with the clb+ strains induced genotoxicity, i.e., the frequencies of micronucleated cells infected with clb+ strain were 4-6 times higher than with the clb- strain. Since the intestinal flora are affected by dietary habits that are strongly associated with ethnicity, these data may contribute to both risk evaluation and prevention of colorectal cancer in the Japanese population.</p>

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