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Development of antibiotics specific for periodontopathogens using inhibitors of a metabolic protein

Research Project

Project/Area Number 20K09930
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57020:Oral pathobiological science-related
Research InstitutionAichi Gakuin University

Principal Investigator

Yoshida Yasuo  愛知学院大学, 歯学部, 准教授 (10315096)

Co-Investigator(Kenkyū-buntansha) 加藤 悦子  東洋大学, 食環境科学部, 教授 (00355752)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords歯周病 / 歯科 / 抗菌薬 / Porphyromonas gingivalis / 薬物
Outline of Research at the Start

本研究課題では、P. gingivalisの代謝酵素を不活化することによって、同菌に特異的に作用する抗菌薬の開発を試みる。具体的には、①ターゲットタンパク質を特異的に阻害する化合物のスクリーニング(製薬企業提供および農研機構所有フッ化物ライブラリーの利用)と②スクリーニングされた候補化合物の臨床応用への検討 (P. gingivalisに対する抗菌効果の検討、他の口腔細菌に対する効果の検討、ヒト細胞への毒性の検討、X線結晶構造解析法を用いた必須タンパク質に対する結合部位の検討)を行い、臨床応用を前提として研究を遂行する。

Outline of Final Research Achievements

With the support of the drug discovery and other advanced technology support platform (BIND) and the Faculty of Food and Environmental Sciences, Toyo University, we focused on the enzymes essential for the growth of the periodontal pathogen Porphyromonas gingivalis, and investigated two types of enzyme-inhibiting compounds. A library (company and fluoride libraries) was used to obtain candidate compounds. The inhibitory effect on the growth of P. gingivalis and oral streptococcus Streptococcus gordonii was examined for multiple enzyme inhibitory compounds. In addition, as a result of biochemical studies using the purified enzyme, one candidate compound suitable as a candidate compound was obtained from a corporate library. In addition, several low-molecular-weight candidate compounds were obtained from the fluoride library. We believe that these results will greatly contribute to the development of periodontal pathogen-specific drugs.

Academic Significance and Societal Importance of the Research Achievements

歯科内科という言葉が使用されて久しい。歯の切削と充填、抜歯や補綴などを行わない内科的治療は理想的であるが、検査法の確立と治療薬の開発とが不可欠である。一般開業医院においてもリアルタイムPCR法を用いた歯周病細菌の検査法が可能になり、診断法は開発されてきたが、歯周病細菌に特異的に作用する抗菌薬は皆無である。本研究では、歯周病原細菌を不活化する薬物を開発し、歯周病の新規予防法や治療法を提起する。

Report

(3 results)
  • 2022 Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (4 results)

All 2021

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 1 results)

  • [Journal Article] Gut bacteria identified in colorectal cancer patients promote tumourigenesis via butyrate secretion2021

    • Author(s)
      Okumura Shintaro、Konishi Yusuke、Narukawa Megumi、Sugiura Yuki、Yoshimoto Shin、Arai Yuriko、Sato Shintaro、Yoshida Yasuo、Tsuji Shunya、Uemura Ken、Wakita Masahiro、Matsudaira Tatsuyuki、Matsumoto Tomonori、Kawamoto Shimpei、Takahashi Akiko、Itatani Yoshiro、Miki Hiroaki ら
    • Journal Title

      Nature Communications

      Volume: 12 Issue: 1 Pages: 5674-5674

    • DOI

      10.1038/s41467-021-25965-x

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of antimicrobial photodynamic therapy on periodontopathogenic bacteria: Evaluation of Rose Bengal and riboflavin as photosensitizers2021

    • Author(s)
      M. Hirose, Y. Yoshida, K. Horii, Y. Hasegawa and Y. Shibuya
    • Journal Title

      The Japanese J. Oral Infec. Dis.

      Volume: 28 Pages: 69-77

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Analysis of the butyrate-producing pathway in Porphyromonas gingivalis.2021

    • Author(s)
      Yoshida Y.
    • Journal Title

      In: Nagano K, Hasegawa Y (eds). Periodontal Pathogens: Methods in Molecular Biology.

      Volume: 2210 Pages: 167-172

    • DOI

      10.1007/978-1-0716-0939-2_16

    • ISBN
      9781071609385, 9781071609392
    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Efficacy of antimicrobial photodynamic therapy with Rose Bengal and blue light against cariogenic bacteria2021

    • Author(s)
      Hirose Marina、Yoshida Yasuo、Horii Kouichiro、Hasegawa Yoshiaki、Shibuya Yasuyuki
    • Journal Title

      Archives of Oral Biology

      Volume: 122 Pages: 105024-105024

    • DOI

      10.1016/j.archoralbio.2020.105024

    • Related Report
      2020 Research-status Report
    • Peer Reviewed

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Published: 2020-04-28   Modified: 2024-01-30  

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