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細菌の情報伝達機構をターゲットとした新しい感染症治療法に関する研究

Research Project

Project/Area Number 16017297
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionToho University

Principal Investigator

舘田 一博  東邦大学, 医学部, 助教授 (20236558)

Co-Investigator(Kenkyū-buntansha) 石井 良和  東邦大学, 医学部, 助手 (90246695)
宮入 伸一  日本大学, 薬学部, 教授 (50209855)
堀川 学  サントリー生物有機科学研究所, 研究員 (70270569)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥5,600,000 (Direct Cost: ¥5,600,000)
Fiscal Year 2005: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2004: ¥2,800,000 (Direct Cost: ¥2,800,000)
Keywords緑膿菌 / Quorum-sensing / Autoinducer / マクロライド
Research Abstract

本研究3年計画の3年目を実施し、以下の項目において研究の成果が得られた。
(1)マクロライド誘導体のQuorum-sensing阻害活性について検討し、いくつかの化合物が強いQuorum-sensing阻害活性を有していることを確認した。(2)Antoinducer分子の誘導体を多数合成してその阻害活性を検討したところ、ある種の化合物が緑膿菌Quorum-sensing機構に対して強い抑制効果を有することを見出した。(3)緑膿菌Quorum-sensing機構に関与する遺伝子(lasI,lasR,rhlI, rhlRなど)のreal time PCR発現評価系により、それぞれの遺伝子発現について検討を加えた。その結果、マクロライド剤によるQuorum-sensing機構の抑制はこれら関連遺伝子の抑制では説明できないことが明らかとなった。これらの知見をもとに、現在マクロライド剤の標的蛋白の探索を行っている。(4)緑膿菌Quorum-sensing機構に関わる蛋白の精製と抗体作成を行い、autoinducer分子C_<12>-HSLのELISAによる定量評価系を確立するとともに、C_<12>-HSLに対するワクチン療法の可能性について検討を加えた。(5)autoinducer分子の生体細胞へ及ぼす影響について検討し、C12-HSLがマクロファージ・好中球に対して強いアポトーシス誘導能があることを確認し、さらにautoinducer分子に対する生体側受容体の探索、およびその細胞内シグナル伝達系への影響について検討を加えた。C12-HSLに対する生体側ターゲット分子の探索に関してはプロテイン・アレイ法およびDNAアレイ法を用いた検討も同時に実施しており、いくつかの候補蛋白が推定されている。

Report

(2 results)
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (12 results)

All 2006 2005 2004

All Journal Article (11 results) Book (1 results)

  • [Journal Article] Synthesis of Pseudomonas quorum-sensing autoinducer analogs and structural entities required for induction of apoptosis in macrophages.2006

    • Author(s)
      Horikawa M. et al.
    • Journal Title

      Bioorg Med Chem Lett.2006 Feb 3 [Epub ahead of print]

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Semi-quantitative analysis of Streptococcus pneumoniae urinary antigen : Kinetics of antigen titers and severity of diseases.2006

    • Author(s)
      Tateda K. et al.
    • Journal Title

      Scand J Infect Dis 38

      Pages: 166-171

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Compensatory response of IL-1 gene knockout mice after pulmonary infection with Klebsiella pneumoniae.2005

    • Author(s)
      Tanabe M. et al.
    • Journal Title

      J Med Microbiol 54

      Pages: 7-13

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Interleukin-1-deficient mice exhibit high sensitivity to gut-derived sepsis caused by Pseudomonas aeruginosa.2005

    • Author(s)
      Horino T. et al.
    • Journal Title

      Cytokine 30

      Pages: 339-349

    • Related Report
      2005 Annual Research Report
  • [Journal Article] An outbreak of Legionella pneumonia originating from a cooling tower.2005

    • Author(s)
      Isozumi R. et al.
    • Journal Title

      Scand J Infect Dis 37

      Pages: 709-711

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Legionella pneumophila evades gamma interferon-mediated growth suppression through interleukin-10 induction in bone marrow-derived macrophages.2005

    • Author(s)
      Yoshizawa S. et al.
    • Journal Title

      Infect Immun 73

      Pages: 2709-2717

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Regulatory effects of macrolides on bacterial virulence : Potential role as quorum-sencing inhibitors.2004

    • Author(s)
      Tateda K, Standiford TJ, Pechere JC, Yamaguchi K.
    • Journal Title

      Current Pharmaceutical Design 10

      Pages: 3055-3065

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Azithromycin Blocks Neutrophil Recruitment in Pseudomonas Endobronchial Infection.2004

    • Author(s)
      Tsai WC, Rodriguez ML, Tateda K.et al.
    • Journal Title

      Am J Respir Crit Care Med 170

      Pages: 1331-1339

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Legionella-induced acute lung injury in the setting of hyperoxia : prcitective role of tumour necrosis factor-alpha.2004

    • Author(s)
      Nara C, Tateda K, et al.
    • Journal Title

      J Med Microbiol 53

      Pages: 727-733

    • Related Report
      2004 Annual Research Report
  • [Journal Article] In vitro Antibacterial Activities of New Fluoroquinolones against Clinical Isolates of Haemophilus influenzae with Ciprofloxacin-Resistance-Associated Alterations in GyrA and ParC.2004

    • Author(s)
      Yoshizumi S, Takahashi Y, Tateda K.et al.
    • Journal Title

      Chemotherapy 50

      Pages: 265-275

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Evaluation of a rapid antigen detection test for Neisseria gonorrhoeae in urine sediment for diagnosis of gonococcal urethritis in males.2004

    • Author(s)
      Suzuki K, Matsumoto T, Murakami H, Tateda K, et al.
    • Journal Title

      J Infect Chemother 10

      Pages: 208-211

    • NAID

      10013505240

    • Related Report
      2004 Annual Research Report
  • [Book] Antibiotics as Anti-Inflammatory and Immunomodulatory Agents.2004

    • Author(s)
      Tateda K, Standiford T.J, Yamaguchi K.
    • Publisher
      Birkhauser
    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2018-03-28  

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