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Exploring the factors of Mycobacterium tuberculosis that function in the dissociation of Rab GTPases from mycobacterial phagosomes

Research Project

Project/Area Number 21790415
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Bacteriology (including Mycology)
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

SETO Shintaro  Hamamatsu University School of Medicine, 医学部, 助教 (50383203)

Project Period (FY) 2009 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2009: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords結核菌 / ファゴソーム / プロテオミクス解析 / 二次元電気泳動 / LC-MS/MS / Mycobacterium tuberculosis / Rab CTPase / マクロファージ / ファゴソーム熟成
Research Abstract

As the candidate of mycobacterial factor that function in the dissociation of Rab GTPases from mycobacterial phagosomes, we focused on the gene Rv3377c. It is reported that Rv3377c product has the cyclase activity for geranylgeranyl moieties. We found that the attenuated strains Mycobacterium tuberculosis H37Ra and Mycobacterium bovis BCG do not express Rv3377c in infected macrophages. Next, we explored the host factors that support the proliferation of M. tuberculosis in the phagosomes in infected macrophages. we carried out the proteomic analysis of mycobacterial phagosomes isolated from infected macrophages. Raw264.7 macrophages were infected with M.tuberculosis, and phagosomal fraction was isolated by sucrose gradient centrifugation. Proteins extracted from mycobacterial phagosomes were subjected to two-dimensional gel electrophoresis and liquid chromatography-tandem mass spectromety. The prominent proteins in the fraction of mycobacterial phagosome were those associated with the endoplasmic reticulum (ER), suggesting that the vesicles derived from ER interact with mycobacterial phagosomes during the inhibition of phagosome maturation.

Report

(3 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report

Research Products

(12 results)

All 2011 2010 2009 Other

All Journal Article (9 results) (of which Peer Reviewed: 4 results) Presentation (3 results)

  • [Journal Article] A novel vaccine strategy to induce mycobacterial antigen-specific Th1 responses by utilizing the C-terminal domain of heat shock protein 70.2011

    • Author(s)
      Uto T, Tsujimura K, Uchijima M, Seto S, Nagata T, Suda T, Chida K, Nakamura H, Koide Y.
    • Journal Title

      FEMS Immunol Med Microbiol 61

      Pages: 189-196

    • Related Report
      2010 Final Research Report
  • [Journal Article] A novel vaccine strategy to induce mycobacterial antigen-specific Th1 responses by utilizing the C-terminal domain of heat shock protein 70.2011

    • Author(s)
      Uto T, Tsujimura K, Uchijima M, Seto S, Nagata T, Suda T, Chida K, Nakamura H, Koide Y.
    • Journal Title

      FEMS Immunol Med Microbiol

      Volume: 61 Pages: 189-196

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rab GTPases regulating phagosome maturation are differentially recruited to mycobacterial phagosomes.2011

    • Author(s)
      Seto S, Tsujimura K, Koide Y.
    • Journal Title

      Traffic

      Volume: (印刷中)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of HLA-DR4-restricted T-cell epitope on MPT51 protein, a major secreted protein derived from Mycobacterium tuberculosis using MPT51 overlapping peptides screening and DNA vaccination.2010

    • Author(s)
      Wang LX, Nagata T, Tsujimura K, Uchijima M, Seto S, Koide Y
    • Journal Title

      Vaccine 23

      Pages: 2026-2031

    • Related Report
      2010 Final Research Report
  • [Journal Article] Differential recruitment of CD63 and Rab7-interacting-lysosomal-protein to phagosomes containing Mycobacterium tuberculosis in macrophages.2010

    • Author(s)
      Seto S, Matsumoto S, Tsujimura K, Koide Y.
    • Journal Title

      Microbiol Immunol. 54

      Pages: 170-174

    • NAID

      10029544344

    • Related Report
      2010 Final Research Report
  • [Journal Article] Identification of HLA-DR4-restricted T-cell epitope on MPT51 protein, a major secreted protein derived from Mycobacterium tuberculosis using MPT51 overlapping peptides screening and DNA vaccination.2010

    • Author(s)
      Wang LX, Nagata T, Tsujimura K, Uchijima M, Seto S, Koide Y.
    • Journal Title

      Vaccine 23

      Pages: 2026-2031

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Differential recruitment of CD63 and Rab7-interacting-lysosomal-protein to phago somes containing Mycobacterium tuberculosis in macrophages.2010

    • Author(s)
      Seto S, Matsumoto S, Tsujimura K, Koide Y.
    • Journal Title

      Microbiol Immunol. 54

      Pages: 170-174

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dissection of Rab7 localization on Mycobacterium tuberculosis phagosome2009

    • Author(s)
      Seto S, Matsumoto S, Ohta I, Tsujimura K, Koide Y.
    • Journal Title

      Biochem Biophys Res Commun 387

      Pages: 272-277

    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Journal Article] Rab GTPases regulating phagosome maturation are differentially recruited to mycobacterial phagosomes.

    • Author(s)
      Seto S, Tsujimura K, Koide Y.
    • Journal Title

      Traffic in press

    • Related Report
      2010 Final Research Report
  • [Presentation] イメージ解析とプロテオミクスによる結核菌ファゴソームの分子解剖2010

    • Author(s)
      瀬戸真太郎、辻村邦夫、小出幸夫
    • Organizer
      第85回日本結核病学会
    • Year and Date
      2010-05-20
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] Proteomic analysis revealed the interaction of Mycobacterium tuberculosis phagosome with endoplasmic reticulum.2010

    • Author(s)
      瀬戸真太郎、辻村邦夫、小出幸夫
    • Organizer
      第83回日本細菌学会総会
    • Year and Date
      2010-03-27
    • Related Report
      2010 Final Research Report
  • [Presentation] Proteomic analysis revealed the interaction of Mycobacterium tuberculosis phagosome with endoplasmic reticulum2010

    • Author(s)
      瀬戸真太郎、辻村邦夫、小出幸夫
    • Organizer
      第83回日本細菌学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2010-03-27
    • Related Report
      2009 Annual Research Report

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Published: 2009-03-31   Modified: 2016-04-21  

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