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Exploitation of proton pumping ATPase inhibitors in oral cavity pathogenic bacteria

Research Project

Project/Area Number 16K18877
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Biological pharmacy
Research InstitutionIwate Medical University

Principal Investigator

Sekiya Mizuki  岩手医科大学, 薬学部, 助教 (70509033)

Research Collaborator 岩本 昌子  長浜バイオ大学, バイオサイエンス学部, 准教授
佐々木 実  岩手医科大学, 歯学部, 教授
阪本 泰光  岩手医科大学, 薬学部, 准教授
Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsプロトン輸送ATPase / F-ATPase / A-ATPase / ポリフェノール / Curcumin / 虫歯 / 歯周病 / う蝕 / プロトン輸送 ATPase / ATP合成酵素 / 薬学 / 感染症 / 酵素 / 細菌 / 生物物理
Outline of Final Research Achievements

In this study, we investigated the roles of proton pump ATPases in the principal causative agent of human dental deseases, S. mutans and P. gingivalis.
We suggested that F-ATPase is an essential role in acid tolerance in S. mutans, and proton gradient and A-ATPase are important for the growth of P. gingivalis. We also found various inhibitors of bacterial proton pump ATPase and suggested their inhibitory mechanism and binding sites.
Furthermore, we analyze the function of lysosomal proton pump V-ATPase in mammalian osteoclast, which associates with bone resorption in periodontal diseases. We found a novel role for the V-ATPase in secretory lysosome trafficking and an unexpected mechanistic link with Rab GTPases.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (9 results)

All 2018 2017 2016 Other

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (5 results) Remarks (1 results)

  • [Journal Article] Porphyromonas gingivalis is highly sensitive to inhibitors of a proton-pumping ATPase.2018

    • Author(s)
      Mizuki Sekiya, Yu Shimoyama, Taichi Ishikawa, Minoru Sasaki, Masamitsu Futai, Mayumi Nakanishi-Matsui.
    • Journal Title

      Biochem. Biophys. Res. Commun

      Volume: 498 Issue: 4 Pages: 837-841

    • DOI

      10.1016/j.bbrc.2018.03.066

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Essential Role of the a3 Isoform of V-ATPase in Secretory Lysosome Trafficking via Rab7 Recruitment2018

    • Author(s)
      Matsumoto N, Sekiya M, Tohyama K, Ishiyama-Matsuura E, Sun-Wada GH, Wada Y, Futai M, Nakanishi-Matsui M.
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 6701-6701

    • DOI

      10.1038/s41598-018-24918-7

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of α/β interface in F1 ATPase rotational catalysis probed by inhibitors and mutation.2017

    • Author(s)
      Sekiya, M., Sakamoto, Y., Futai, M., Nakanishi-Matsui, M.
    • Journal Title

      Int. J. Biol. Macromol.

      Volume: 99 Pages: 615-621

    • DOI

      10.1016/j.ijbiomac.2017.02.089

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] プロトン輸送ATPase阻害剤は虫歯菌Streptococcus mutansの耐酸性を低下させる2018

    • Author(s)
      關谷瑞樹、泉澤信太郎、櫛桁安生、芳賀雅人、下山佑、佐々木実、木村重信、佐々木由香、岩本昌子、中西(松井)真弓
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 破骨細胞における分泌リソソームの局在に対するV-ATPase阻害剤(バフィロマイシンA1)の影響2018

    • Author(s)
      松元奈緒美、關谷瑞樹、中西(松井)真弓
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] プロトン輸送ATPaseを標的とした抗う蝕化合物の探索2017

    • Author(s)
      泉澤信太郎、關谷瑞樹、櫛桁安生、芳賀雅人、下山佑、木村重信、佐々木由香、岩本昌子、中西(松井)真弓
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-26
    • Related Report
      2016 Research-status Report
  • [Presentation] Streptococcus mutansの耐酸性におけるF-ATPaseの重要性2017

    • Author(s)
      關谷瑞樹、泉澤信太郎、櫛桁安生、芳賀雅人、下山佑、佐々木実、木村重信、佐々木由香、岩本昌子、中西(松井)真弓
    • Organizer
      ConBio2017
    • Related Report
      2017 Annual Research Report
  • [Presentation] クルクミン類による ATP 合成酵素阻害作用2016

    • Author(s)
      關谷瑞樹、山野辺春香、千葉瑛子、佐藤桃恵、河野富一、大橋暁香、小川智、山越博幸、岩渕俊治、二井將光、中西(松井)真弓
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台
    • Year and Date
      2016-09-26
    • Related Report
      2016 Research-status Report
  • [Remarks] 骨粗鬆症など骨代謝異常症の治療に つながる骨吸収のメカニズムを解明

    • URL

      http://www.iwate-med.ac.jp/news/n5-research/kikaku-180501/

    • Related Report
      2017 Annual Research Report

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Published: 2016-04-21   Modified: 2019-03-29  

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