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細菌感染とメンブレントラフィック

Research Project

Project/Area Number 19041045
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionIwate Medical University

Principal Investigator

津田 香代子  Iwate Medical University, 薬学部, 助手 (30444524)

Co-Investigator(Kenkyū-buntansha) 吉森 保  大阪大学, 微生物病研究所, 教授 (60191649)
古田 信道  大阪大学, 歯学研究科, 助教 (50452446)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥8,100,000 (Direct Cost: ¥8,100,000)
Fiscal Year 2008: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2007: ¥4,000,000 (Direct Cost: ¥4,000,000)
Keywords菌感染 / オートファジー / 細胞内輸送 / SNARE / 感染防御 / Porphyromonas gingivalis / 脂質ラフト / α5β1 integrin / Rab7
Research Abstract

メンブレントラフィック(エンドサイトーシス及びオートファジー)の菌感染に与える影響について歯周病菌Porphyromonas finfivalis(Pg)及びA群レンサ球菌を用いた解析を行った。1.菌感染とエンドサイトーシス ; Pgによって恒常的に細胞外に放出されたmembrane vesicles(MVs)細胞はLPS、線毛等の菌表層成分を保持しており、菌自体の侵入と同様にPg-MVsの宿主細胞内への侵入も歯周病の発症、進行に深く寄与すると考えられている。そこで、Pg-MVsの細胞内侵入機構及び宿主細胞に与える毒性について解析を行った。まず、Pg-MVsのHeLa細胞への取り込みには宿主のPI3キナーゼ、small GTPase Racが介在するアクチン機能及び、細胞膜ドメインである脂質ラフトが必須であり、エンドサイトーシス制御因子であるクラスリンやダイナミンの機能は関与しない事を見出した。また、細胞内においてPg-MVsがもつプロテアーゼが宿主細胞のトランスフェリン受容体や接着班複合体タンパク質(FACP ; paxilin and focal adhesion kinase)が分解し、細胞運動と増殖の阻害といった細胞毒性を発揮する事も明らかにした。
2. 菌感染とオートファジー ; 細胞内に侵入したA群レンサ球菌(group A Streptoccus, GAS)のオートファジーによる捕獲分解システムについての解析を続行した。共焦点レーザー顕微鏡を利用したスクリーニングから、細胞内GASを包むオートファゴソームであるGcAV(GAS containing LC3 posltiveautophagosome like vacuole)が最終的に分解オルガネラであるリソソームと融合し、オートリソソームに変化する過程に必須なSNARE蛋白質の同定に成功した。

Report

(2 results)
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • Research Products

    (30 results)

All 2009 2008 2007 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results) Presentation (19 results) Book (2 results) Remarks (3 results)

  • [Journal Article] Effect of Helicobacter pylori's vacuolating cytotoxin on the autophagy pathway in gastric epithelial cells.2009

    • Author(s)
      Terebiznik MR, et.al.
    • Journal Title

      Autophagy Apr 19 : 5 (3)(Epub ahead of print)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Functional Analysis of a5i31 Integrin and Lipid Rafts in Invasion of Epithelial Cells by Porphyromonas gingivalis using Fluorescent Beads Coated with Bacterial Membrane Vesicle.2008

    • Author(s)
      Tsuda K, et.al.
    • Journal Title

      Cell Struct Funct. 33

      Pages: 109-122

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Relationship of Porphyromonas gingivalis with glycemic level in patients with type 2 diabetes following periodontal treatment.2008

    • Author(s)
      Makiura N, et.al.
    • Journal Title

      Oral Microbiology and Immunology 23(4)

      Pages: 348-351

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Autophagic control of listeria through intracellular innate immune recogni Lion in drosophila.2008

    • Author(s)
      Yano T, et.al.
    • Journal Title

      Nat Immunol. 9

      Pages: 908-916

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Maturation of fimbria precursor protein by exogenous gingipains in Porphyromonas gingivalis gingipain-null mutant.2007

    • Author(s)
      Kato T, Tsuda T, Omori H, Kato T, Yoshimori T, Amano A.
    • Journal Title

      FEMS Microbiol Lett. 3

      Pages: 452-460

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dissection of the autophagosome maturation process by a novel reporter protein, tandem fluorescent-tagged LC3.2007

    • Author(s)
      Kimura S, Noda T, Yoshimori T.
    • Journal Title

      Autophagy. 3

      Pages: 452-460

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] 細胞内自己消化システム・オマトファジーによる生体防御2008

    • Author(s)
      吉森保
    • Organizer
      日本細菌学会関東支部総会特別講演
    • Place of Presentation
      生命の森リゾート(千葉)
    • Year and Date
      2008-10-24
    • Related Report
      2008 Annual Research Report
  • [Presentation] porphuromonas gingibalis病原性膜小胞の細胞侵入と細胞傷害性の解析2008

    • Author(s)
      古田信道
    • Organizer
      第50回歯科基礎医学会学術大会・総会
    • Place of Presentation
      東京
    • Year and Date
      2008-09-23
    • Related Report
      2008 Annual Research Report
  • [Presentation] Invasion of host cells by membrane vesicles of Porphyromonas gingivalis2008

    • Author(s)
      津田香代子
    • Organizer
      第7回あわじしま感染症、免疫フォーラム
    • Place of Presentation
      兵庫県立淡路夢舞台国際会議場
    • Related Report
      2008 Annual Research Report
  • [Presentation] Autophagy : Molecular Machinery and Role in Cellular Defense2008

    • Author(s)
      Tamotsu Yoshimori
    • Organizer
      Korean Society of Medical Biochemistry and Molecular Biology Annual International Conference : In Commemoration of the 60th KSMBMB Anniversary, Symposium SY17 : Autophagy and Human Diseases
    • Place of Presentation
      Seoul, Korea
    • Related Report
      2008 Annual Research Report
  • [Presentation] Mechanistic Insight into Membrane Dynamics in Mammalian Autophagy2008

    • Author(s)
      Tamotsu Yoshimori
    • Organizer
      Center for the Study of InflaMmatory Bowel Disease 18th Annual Workshop on Autophagy in Immunity
    • Place of Presentation
      Boston, USA
    • Related Report
      2008 Annual Research Report
  • [Presentation] Molecular Machinery of Autophagy and Its Role in Diseases2008

    • Author(s)
      Tamotsu Yoshimori
    • Organizer
      11th Western Pacific Cingress on Chemotherapy and Infectious Diseases, Symposium 9 : Invasive Gro up A Streptococcal Infections
    • Place of Presentation
      Taipei, Taiwan
    • Related Report
      2008 Annual Research Report
  • [Presentation] Autophagy as a Cellular Defense System against Pathogens and Unfolding Proteins2008

    • Author(s)
      Tamotsu YoshiMori
    • Organizer
      BMB2008(第31回日本分子生物学会年会・第81回日本生化学会大会合同大会)Sympos ium 3S3 : Intracellular Logistics : APProach to Pathophy siology of Membrane Traffic
    • Place of Presentation
      神戸ホーピアホテル
    • Related Report
      2008 Annual Research Report
  • [Presentation] Autophagy as A Cellular Defense System2007

    • Author(s)
      Tamotsu Yoshimori
    • Organizer
      2007 International RIMD-CVRDC Joint Symposium
    • Place of Presentation
      Osaka, Japan
    • Year and Date
      2007-12-18
    • Related Report
      2007 Annual Research Report
  • [Presentation] オートファジー:分子機構と疾患における役割2007

    • Author(s)
      吉森 保
    • Organizer
      大阪大学21世紀COE「疾患関連糖鎖・タンパク質の統合的機能解析」若手セミナー
    • Place of Presentation
      大阪大学医学部
    • Year and Date
      2007-10-24
    • Related Report
      2007 Annual Research Report
  • [Presentation] オートファジー:生体防御にも働く細胞内自己消化システム2007

    • Author(s)
      吉森 保
    • Organizer
      家畜DNA西郷シンポジウム
    • Place of Presentation
      福島県西白河郡
    • Year and Date
      2007-10-02
    • Related Report
      2007 Annual Research Report
  • [Presentation] 生体防御機構としてのオートファジー:細菌感染とフォールディング病2007

    • Author(s)
      吉森 保
    • Organizer
      文科省科研費特定領域研究「タンパク質分解による細胞・個体機能の制御」公開シンポジウム「オートファジー:病態に迫る!」
    • Place of Presentation
      東京
    • Year and Date
      2007-09-22
    • Related Report
      2007 Annual Research Report
  • [Presentation] Autophagy: new insights into its molecular machinery and functions2007

    • Author(s)
      Tamotsu Yoshimori
    • Organizer
      The invited seminar in Institute of Molecular and Cell Biology
    • Place of Presentation
      Singapore
    • Year and Date
      2007-09-12
    • Related Report
      2007 Annual Research Report
  • [Presentation] 生体防御とオートファジー2007

    • Author(s)
      吉森 保
    • Organizer
      第18回日本生体防御学会学術総会特別講演
    • Place of Presentation
      福岡
    • Year and Date
      2007-07-26
    • Related Report
      2007 Annual Research Report
  • [Presentation] ベールを脱ぐオートファジー:生体防御にも働く細胞内自己消化システム2007

    • Author(s)
      吉森 保
    • Organizer
      熊本大学大学院医学教育部セミナー
    • Place of Presentation
      熊本大学大学院医学教育部
    • Year and Date
      2007-07-04
    • Related Report
      2007 Annual Research Report
  • [Presentation] Molecular analysis of internalization of Porphyromonas gingivalis by cells using fluorescent beads coated with bacterial membrane vesicle2007

    • Author(s)
      津田 香代子
    • Organizer
      第7回あわじしま感染症、免疫フォーラム
    • Place of Presentation
      兵庫県立淡路夢舞台国際会議場
    • Related Report
      2007 Annual Research Report
  • [Presentation] New insight into Molecular Mechanisms of the Canonical and Specialized Autophagy2007

    • Author(s)
      Tamotsu Yoshimori
    • Organizer
      Keystone Symposia on "Autophagy in Health and Disease"
    • Place of Presentation
      Monterey, California, U.S.A.
    • Related Report
      2007 Annual Research Report
  • [Presentation] Autophagy as a cellular guardian against bacteria and aggregate-prone proteins2007

    • Author(s)
      Tamotsu Yoshimori
    • Organizer
      ELSO conference 2007, Subgroup meeting one-Autophagy
    • Place of Presentation
      Dresden, Germany
    • Related Report
      2007 Annual Research Report
  • [Presentation] Autophagy: Molecular Machinery and Role in Cellular Defense2007

    • Author(s)
      Tamotsu Yoshimori
    • Organizer
      The 20th Naito Conference on "Innate Immunity in Medicine and Biology III"
    • Place of Presentation
      Kanagawa, Japan
    • Related Report
      2007 Annual Research Report
  • [Presentation] Membrane Dynamics and Cellular Defense Function of Autophagy2007

    • Author(s)
      Tamotsu Yoshimori
    • Organizer
      Internatinal Symposium on Membrane Traffic
    • Place of Presentation
      Awajishima, Japan
    • Related Report
      2007 Annual Research Report
  • [Book] 分子細胞生物学辞典(第2版)2008

    • Author(s)
      吉森保
    • Publisher
      (株)東京化学同人
    • Related Report
      2008 Annual Research Report
  • [Book] 生化学辞典(第4版)リソソームへの輸送2007

    • Author(s)
      吉森 保
    • Total Pages
      1616
    • Publisher
      (株)東京化学同人
    • Related Report
      2007 Annual Research Report
  • [Remarks]

    • URL

      http://www.biken.osaka-u.ac.jp/act/act_yoshimori.php

    • Related Report
      2008 Annual Research Report
  • [Remarks]

    • URL

      http://www.dent.osaka-u.ac.jp/~methodol

    • Related Report
      2008 Annual Research Report
  • [Remarks]

    • URL

      http://www.biken.osaka-u.ac.jp/act_yoshimori.php

    • Related Report
      2007 Annual Research Report

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Published: 2007-04-01   Modified: 2018-03-28  

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