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Development of a new method for prevention of colorectal cancer by eliminating colibactin-producing bacteria

Research Project

Project/Area Number 21K19666
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 58:Society medicine, nursing, and related fields
Research InstitutionNational Institute of Infectious Diseases

Principal Investigator

Kiga Kotaro  国立感染症研究所, 治療薬・ワクチン開発研究センター, 室長 (90738246)

Co-Investigator(Kenkyū-buntansha) 佐藤 祐介  麻布大学, 獣医学部, 講師 (20757265)
崔 龍洙  自治医科大学, 医学部, 教授 (50306932)
小野 久弥  北里大学, 獣医学部, 准教授 (80704569)
Project Period (FY) 2021-07-09 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2023: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2022: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2021: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsバクテリオファージ / 大腸がん / コリバクチン産生大腸菌 / コリバクチン / 大腸菌 / 細菌感染症 / 下痢 / 腸内細菌叢 / マーモセット
Outline of Research at the Start

大腸がんはわが国で最も罹患率の高いがんである。近年、大腸がん発症の一因が、大腸菌由来の『コリバクチン(毒素ペプチド)』にあるという報告が相次いだ。しかし、コリバクチン由来の大腸がんを防ぐ手法は未だ開発されていない。このような背景の中、我々は、特定の遺伝子を有する細菌を選択的に殺菌する抗菌ファージ技術を発表した(Kiga K. et al., Nat Commun. 2020)。本技術を用いれば、腸内細菌叢からコリバクチン産生性大腸菌を選択的に除去できる。本研究では、独自に開発した抗菌ファージ製剤を用い、大腸がん発症のリスクファクターであるコリバクチン産生性大腸菌の駆除を目指す。

Outline of Final Research Achievements

We identified and evaluated the efficacy of phages that specifically target and kill colibactin-producing Escherichia coli. From 200 screened phages, we selected three phages that exhibited high lytic activity against colibactin-producing E. coli isolated from common marmosets. Of the 20 marmoset fecal samples, four were found to harbor colibactin-producing bacteria. Colibactin-producing E. coli was colonized in four marmosets, and then they were administered with antimicrobial phages. As a result, the bacterial count decreased in three marmosets. Further research toward practical application is expected to establish a new method for the prevention and treatment of colorectal cancer.

Academic Significance and Societal Importance of the Research Achievements

本研究は、特定の細菌に感染するファージを用いた革新的な治療法の確立に寄与するものである。特に、コリバクチン産生性大腸菌を標的とすることで、大腸がんの発症メカニズム解明とその予防・治療の新たな道を開く可能性がある。また、ファージ療法の効果を霊長類で確認することにより、ヒトへの応用に向けた重要な知見を提供した。大腸がんは世界中で高い罹患率と死亡率を誇る深刻な疾患であり、効果的な予防および治療法の開発が急務である。本研究で得られた成果は、コリバクチン産生性大腸菌を除去する新たな方法として、将来的に大腸がんの予防に大きく貢献する可能性がある。

Report

(2 results)
  • 2023 Final Research Report ( PDF )
  • 2021 Research-status Report
  • Research Products

    (25 results)

All 2022 2021

All Journal Article (15 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 10 results,  Open Access: 10 results) Presentation (9 results) (of which Invited: 4 results) Book (1 results)

  • [Journal Article] Interspecies Regulation Between Staphylococcus caprae and Staphylococcus aureus Colonized on Healed Skin After Injury2022

    • Author(s)
      Ogura Kohei、Furuya Hiroka、Takahashi Natsuki、Shibata Kana、Endo Maho、Watanabe Shinya、Cui Longzhu、Miyoshi-Akiyama Tohru、Okamoto Shigefumi、Ogai Kazuhiro、Sugama Junko
    • Journal Title

      Frontiers in Microbiology

      Volume: 13 Pages: 999-999

    • DOI

      10.3389/fmicb.2022.818398

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Distribution of Extended-Spectrum β-Lactamase Genes and Antimicrobial Susceptibility among Residents in Geriatric Long-Term Care Facilities in Japan2021

    • Author(s)
      Akine Dai、Sasahara Teppei、Kiga Kotaro、Ae Ryusuke、Kosami Koki、Yoshimura Akio、Kubota Yoshinari、Sasaki Kazumasa、Kimura Yumiko、Ogawa Masanori、Watanabe Shinya、Morisawa Yuji、Cui Longzhu
    • Journal Title

      Antibiotics

      Volume: 11 Issue: 1 Pages: 36-36

    • DOI

      10.3390/antibiotics11010036

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bacteriophages as Solid Tumor Theragnostic Agents2021

    • Author(s)
      Veeranarayanan Srivani、Azam Aa Haeruman、Kiga Kotaro、Watanabe Shinya、Cui Longzhu
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23 Issue: 1 Pages: 402-402

    • DOI

      10.3390/ijms23010402

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bacteriophage Technology and Modern Medicine2021

    • Author(s)
      Azam Aa Haeruman、Tan Xin-Ee、Veeranarayanan Srivani、Kiga Kotaro、Cui Longzhu
    • Journal Title

      Antibiotics

      Volume: 10 Issue: 8 Pages: 999-999

    • DOI

      10.3390/antibiotics10080999

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A bacterial small RNA regulates the adaptation of Helicobacter pylori to the host environment2021

    • Author(s)
      Kinoshita-Daitoku, R., Kiga, K., Miyakoshi, M. et al.
    • Journal Title

      Nature Communications

      Volume: 12 Issue: 1 Pages: 2085-2085

    • DOI

      10.1038/s41467-021-22317-7

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Investigation of <i>Staphylococcus aureus</i> positive for Staphylococcal enterotoxin S and T genes2021

    • Author(s)
      SATO’O Yusuke、OMOE Katsuhiko、AIKAWA Yasuko、KANO Mayuko、ONO Hisaya K.、HU Dong-Liang、NAKANE Akio、SUGAI Motoyuki
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: 83 Issue: 7 Pages: 1120-1127

    • DOI

      10.1292/jvms.20-0662

    • NAID

      130008064538

    • ISSN
      0916-7250, 1347-7439
    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Influenza Outbreak and a Group Meal in a Geriatric Long-term Care Facility in Japan2021

    • Author(s)
      YOSHIMURA AKIO、SASAHARA TEPPEI、AE RYUSUKE、KOSAMI KOKI、AKINE DAI、OGAWA MASANORI、HAMABATA KENJI、HATAKEYAMA SHUJI、MORISAWA YUJI、CUI LONGZHU
    • Journal Title

      Biocontrol Science

      Volume: 26 Issue: 4 Pages: 207-210

    • DOI

      10.4265/bio.26.207

    • NAID

      130008140118

    • ISSN
      1342-4815, 1884-0205
    • Related Report
      2021 Research-status Report
  • [Journal Article] Prolonged carriage of ESBL-producing enterobacterales and potential cross-transmission among residents in geriatric long-term care facilities2021

    • Author(s)
      Ae Ryusuke、Sasahara Teppei、Yoshimura Akio、Kosami Koki、Hatakeyama Shuji、Sasaki Kazumasa、Kimura Yumiko、Akine Dai、Ogawa Masanori、Hamabata Kenji、Cui Longzhu
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1

    • DOI

      10.1038/s41598-021-01190-w

    • Related Report
      2021 Research-status Report
  • [Journal Article] Role of CRISPR-Cas system on antibiotic resistance patterns of Enterococcus faecalis2021

    • Author(s)
      Gholizadeh Pourya、Aghazadeh Mohammad、Ghotaslou Reza、Rezaee Mohammad Ahangarzadeh、Pirzadeh Tahereh、Cui Longzhu、Watanabe Shinya、Feizi Hadi、Kadkhoda Hiva、Kafil Hossein Samadi
    • Journal Title

      Annals of Clinical Microbiology and Antimicrobials

      Volume: 20 Issue: 1 Pages: 999-999

    • DOI

      10.1186/s12941-021-00455-6

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Complete Genome Sequencing of Mycobacterium heckeshornense Strain JMUB5695, Isolated from Necrotizing Granulomatous Lesions2021

    • Author(s)
      Katahira Katsuyuki、Watanabe Shinya、Wakamatsu Kentaro、Nagasawa Zenzo、Kawasaki Masayuki、Cui Longzhu
    • Journal Title

      Microbiology Resource Announcements

      Volume: 10 Issue: 27

    • DOI

      10.1128/mra.00141-21

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Retention, Bacterial Adhesion, and Biofilm Formation between Anionic and Zwitterionic Bandage Contact Lenses in Healthy Dogs: A Pilot Study2021

    • Author(s)
      Kita Mizuki、Kanai Kazutaka、Ono Hisaya K.、Otaka Yuya、Okada Daiki、Nagai Noriaki、Kudo Rina、Yamashita Yohei、Hino Shiori、Matsunaga Toru、Tajima Kazuki
    • Journal Title

      Veterinary Sciences

      Volume: 8 Issue: 10 Pages: 238-238

    • DOI

      10.3390/vetsci8100238

    • Related Report
      2021 Research-status Report
  • [Journal Article] High production of egc2-related staphylococcal enterotoxins caused a food poisoning outbreak2021

    • Author(s)
      Umeda Kaoru、Ono Hisaya K.、Wada Takayuki、Motooka Daisuke、Nakamura Shota、Nakamura Hiromi、Hu Dong-Liang
    • Journal Title

      International Journal of Food Microbiology

      Volume: 357 Pages: 109366-109366

    • DOI

      10.1016/j.ijfoodmicro.2021.109366

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Vaginal mucus in mice: developmental and gene expression features of epithelial mucous cells during pregnancy2021

    • Author(s)
      Sugiyama Makoto、Machida Nao、Yasunaga Arata、Terai Nanako、Fukasawa Hanae、Ono Hisaya K、Kobayashi Ryosuke、Nishiyama Keita、Hashimoto Osamu、Kurusu Shiro、Yoshioka Kazuki
    • Journal Title

      Biology of Reproduction

      Volume: 105 Issue: 5 Pages: 1272-1282

    • DOI

      10.1093/biolre/ioab157

    • Related Report
      2021 Research-status Report
  • [Journal Article] Characteristics of systemic infection and host responses in chickens experimentally infected with <i>Salmonella enterica</i> serovar Gallinarum biovar Gallinarum2021

    • Author(s)
      OJIMA Shinjiro、OKAMURA Masashi、OSAWA Nana、TAMURA Akiko、YOSHIOKA Kazuki、KASHIMOTO Takashige、HANEDA Takeshi、ONO Hisaya K.、HU Dong-Liang
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: 83 Issue: 7 Pages: 1147-1154

    • DOI

      10.1292/jvms.21-0227

    • NAID

      130008068193

    • ISSN
      0916-7250, 1347-7439
    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Studies on the biological activities and emetic mechanism of staphylococcal enterotoxins2021

    • Author(s)
      ONO Hisaya
    • Journal Title

      Nippon Saikingaku Zasshi

      Volume: 76 Issue: 2 Pages: 139-148

    • DOI

      10.3412/jsb.76.139

    • NAID

      130008042878

    • ISSN
      0021-4930, 1882-4110
    • Related Report
      2021 Research-status Report
  • [Presentation] バクテリオファージを利用した細菌感染症の治療2021

    • Author(s)
      氣駕 恒太朗
    • Organizer
      第461回 北里大学獣医学科セミナー<Cutting Edge>
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] クロストーク法によるKlebsiella pneumoniaeに対する広感染宿主域ファージの分離2021

    • Author(s)
      佐藤祐介、氣駕恒太朗、渡邉真弥、Tanit Boonsiri、李峰宇、相羽由詞、李俊傑、Azam Haeruman、笹原鉄平、崔龍洙
    • Organizer
      日本ファージセラピー研究会 第1回研究集会
    • Related Report
      2021 Research-status Report
  • [Presentation] 抗菌カプシドの殺菌活性向上に向けたCRISPR-Cas13aの最適化2021

    • Author(s)
      西川裕太郎、氣駕恒太朗、渡邉真弥、鈴木貴子、下條誉幸、崔龍洙
    • Organizer
      日本ファージセラピー研究会 第1回研究集会
    • Related Report
      2021 Research-status Report
  • [Presentation] バクテリオファージを利用した次世代創薬研究2021

    • Author(s)
      氣駕 恒太朗
    • Organizer
      iSeminar
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] バクテリオファージを用いた疾患治療法の開発2021

    • Author(s)
      氣駕 恒太朗
    • Organizer
      千里ライフサイエンスセミナー
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 細菌遺伝子検査用CRISPR-Cas13抗菌カプシドの作製条件の最適化2021

    • Author(s)
      西川 裕太郎, 氣駕 恒太朗, 渡邊 真弥, 須藤 貴子, 下條 誉幸, 崔 龍洙
    • Organizer
      第69回 日本化学療法学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] メチシリン耐性黄色ブドウ球菌(MRSA)のmprF変異はダプトマイシンとバンコマイシンの交差耐性に寄与する2021

    • Author(s)
      ティティアナンパコーン カネート, 渡邊 真弥, 笹原 鉄平, 氣駕 恒太朗, 相羽 由詞, 崔 龍洙
    • Organizer
      第69回 日本化学療法学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] オキサシリン感性mecA陽性黄色ブドウ球菌のオキサシリン耐性化に関わる変異遺伝子の同定と評価2021

    • Author(s)
      渡邊 真弥, Kanate Thitiananpakorn, 相羽 由詞, 氣駕 恒太朗, 笹原 鉄平, 崔 龍洙
    • Organizer
      第69回 日本化学療法学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] ファージを創る:次世代抗菌治療法の開発2021

    • Author(s)
      氣駕 恒太朗
    • Organizer
      早稲田大学 学術講演
    • Related Report
      2021 Research-status Report
    • Invited
  • [Book] 創薬研究者・アカデミア研究者が知っておくべき最新の免疫学とその応用技術2021

    • Author(s)
      執筆者:101名、技術情報協会
    • Total Pages
      598
    • Publisher
      技術情報協会
    • ISBN
      4861048567
    • Related Report
      2021 Research-status Report

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Published: 2021-07-13   Modified: 2025-01-30  

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