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Salmonella effector GogA induces caspase-8 activation, leading to modulation of proinfallamatory response in macrophages

Research Project

Project/Area Number 23689026
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Bacteriology (including Mycology)
Research InstitutionChiba University

Principal Investigator

TAKAYA Akiko  千葉大学, 薬学研究科(研究院), 准教授 (80334217)

Co-Investigator(Renkei-kenkyūsha) YAMAMOTO Tomoko  千葉大学, 大学院薬学研究院, 教授 (60110342)
SATO Yoshiharu  千葉大学, 大学院薬学研究院, 助教 (00554586)
Project Period (FY) 2011-11-18 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Fiscal Year 2013: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2012: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Keywordsサルモネラ / カスパーゼ-8 / 炎症反応 / 細胞死 / エフェクター / SPI1エフェクター / 骨髄細胞 / GogA / カスパーゼ-8 / RNAヘリカーゼ / カスパーゼー8 / SPI1 / SPI2
Research Abstract

Caspase-8 activation requires tight regulation owing to its two opposing functions, namely as an initiator of apoptosis and in a non-apoptotic role including induction of the pro-inflammatory response. We have demonstrated that a novel Salmonella effector GogA induces caspase-8 activation. The limited caspase-8 activation by GogA is involved in NFkB activation, leading to modulation of proinflammatory cytokines at the early stage of Salmonella infection. However, caspase-8 activation is not involved in induction of pyroptosis. Furthermore, caspase-8 activation by GogA may be required for interaction with LSm8, U6 snRNA-associated Sm-like protein. On the other hand, Salmonella has another effector involving in caspase-8 activation in addition of GogA. These finding together, it is suggested that induction of NFkB activation by the activated-caspase-8 are regulated through translocation of some effectors including GogA, leading to proliferation of Salmonella within host cells.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (42 results)

All 2014 2013 2012 2011 Other

All Journal Article (13 results) (of which Peer Reviewed: 8 results) Presentation (27 results) (of which Invited: 6 results) Remarks (2 results)

  • [Journal Article] サルモネラ感染症のメカニズム2014

    • Author(s)
      高屋明子、山本友子
    • Journal Title

      感染症内科

      Volume: (2頁未定)

    • Related Report
      2013 Final Research Report
  • [Journal Article] サルモネラ感染症の発症メカニズム2014

    • Author(s)
      高屋明子、山本友子
    • Journal Title

      感染症内科

      Volume: 2

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Regulation of Salmonella pathogenesis by effectors of Salmonella pathogenicity island 1 and 22013

    • Author(s)
      Takaya, A
    • Journal Title

      Antibiotics and Chemotherapy

      Volume: 29 Pages: 62-71

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Studies on the molecular mechanism of Salmonella infection2013

    • Author(s)
      Yamamoto T
    • Journal Title

      Antibiotics and Chemotherapy

      Volume: 29 Pages: 473-483

    • Related Report
      2013 Final Research Report
  • [Journal Article] Methylation of 23S rRNA nucleotide G748 by RlmA^<II> methyltransferase renders Streptococcus pneumoniae telithromycin susceptible2013

    • Author(s)
      Takaya A, Sato Y, Shoji T, Yamamoto T
    • Journal Title

      Antimicoriol agents Chemother

      Volume: 57 Pages: 3789-3796

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Methylation of 23S rRNA Nucleotide G748 by RlmAII Methyltransferase Renders Streptococcus pneumoniae Telithromycin Susceptible.2013

    • Author(s)
      Takaya A, Sato Y, Shoji T, Yamamoto T
    • Journal Title

      Antimicrob Agents Chemother

      Volume: 57 Issue: 8 Pages: 3789-3796

    • DOI

      10.1128/aac.00164-13

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of Salmonella pathogenesis by effectors of Salmonella pathogenicity island 1 and 2.2013

    • Author(s)
      Takaya, A.
    • Journal Title

      Antibiotics & Chemotherapy

      Volume: 29 Pages: 62-71

    • Related Report
      2012 Annual Research Report
  • [Journal Article] Studies on the molecular mechanism of Salmonella infection.2013

    • Author(s)
      Yamamoto, T.
    • Journal Title

      Antibiotics & Chemotherapy

      Volume: 29 Pages: 473-483

    • Related Report
      2012 Annual Research Report
  • [Journal Article] Hughes KT : "YdiV : a dual function protein that targets FlhDC for ClpXP-dependent degradation by promoting release of DNA-bound FlhDC complex"2012

    • Author(s)
      Takaya A, Erhardt M, Karata K, Winterberg K, Yamamoto T
    • Journal Title

      Mol Microbiol

      Volume: 83(6) Pages: 1268-84

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] YdiV : a dual function protein that targets FlhDC for ClpXP-dependent degradation by promoting release of DNA-bound FlhDC complex2012

    • Author(s)
      Takaya A, Erhardt M, Karata K, Winterberg K, Yamamoto T, Hughes KT
    • Journal Title

      Mol Microbiol

      Volume: 83(6) Issue: 6 Pages: 1268-84

    • DOI

      10.1111/j.1365-2958.2012.08007.x

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Meta-analytic approach to the accurate prediction of secreted virulence effectors in gram-negative bacteria2011

    • Author(s)
      Sato Y, Takaya A, Yamamoto T
    • Journal Title

      BMC Bioinformatics

      Volume: 14 Pages: 442-442

    • Related Report
      2013 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dual regulatory pathways of flagellar gene expression by ClpXP protease in enterohaemorrhagic2011

    • Author(s)
      Kitagawa R, Takaya A, Yamamoto T
    • Journal Title

      Escherichia coli. Microbiology

      Volume: 157 Pages: 3094-103

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Dual regulatory pathways of flagellar gene expression by ClpXP protease in enterohaemorrhagic Escherchia coli2011

    • Author(s)
      Kitagawa R, Takaya A, Yamamoto T
    • Journal Title

      Microbiology

      Volume: 157 Issue: 11 Pages: 3094-3103

    • DOI

      10.1099/mic.0.051151-0

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] The function and regulation of Salmonella pathogenicity islands 1and 2 in host cells2014

    • Author(s)
      高屋明子
    • Organizer
      第87回日本細菌学会総会
    • Place of Presentation
      東京
    • Related Report
      2013 Final Research Report
    • Invited
  • [Presentation] FliT enhances the ClpXP-catalyzed degradation of masterregulator FlhD_4C_2 in Salmonella2014

    • Author(s)
      佐藤慶治
    • Organizer
      第87回日本細菌学会総会
    • Place of Presentation
      東京
    • Related Report
      2013 Final Research Report
  • [Presentation] 肺炎球菌のテリスロマイシン感受性に寄与するrRNA段階的修飾2014

    • Author(s)
      庄司竜麻
    • Organizer
      第87回日本細菌学会総会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] The function and regulation of Salmonella pathogenicity islands1 and 2 in host cells.2014

    • Author(s)
      高屋明子、佐藤慶治、山本友子
    • Organizer
      第87回日本細菌学会総会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] FliT enhances the ClpXP-catalyzed degradation of masterregulator FlhD4C2 in Salmonella.2014

    • Author(s)
      佐藤慶治、高屋明子、山本友子
    • Organizer
      第87回日本細菌学会総会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] リネゾリド長期投与におけるリネゾリド耐性Coagulase-negative Staphylococccusの出現と耐性化機構2013

    • Author(s)
      木村旭
    • Organizer
      第96回日本細菌学会関東支部総会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] サルモネラFliTによるClpXPプロテアーゼ依存的FlhC分解促進機構2013

    • Author(s)
      小田倉香織
    • Organizer
      第96回日本細菌学会関東支部総会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] サルモネラ新規エフェクターSTM1239の同定2013

    • Author(s)
      松井優里
    • Organizer
      第96回日本細菌学会関東支部総会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] FliT fine-tunes the flagellar biogenesis by enhancing the ClpXP-catalyzed degradation of master regulator2013

    • Author(s)
      Takaya A
    • Organizer
      FlhD_4C_2.EMBO workshop on AAA+ proteins : from mechanism and disease to targets
    • Place of Presentation
      Neuss, Germany
    • Related Report
      2013 Final Research Report
  • [Presentation] 肺炎球菌リボソームとTELの相互作用におけるリボソーム内因性修飾酵素の影響2013

    • Author(s)
      庄司竜麻
    • Organizer
      第7回細菌学若手コロッセウム
    • Place of Presentation
      広島
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] CspC/CspEによるサルモネラの病原性発現制御2013

    • Author(s)
      前田侑也
    • Organizer
      第7回細菌学若手コロッセウム
    • Place of Presentation
      広島
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] 協調的認識により調節されるAAA+プロテアーゼClpXPの基質特異性2013

    • Author(s)
      佐藤慶治
    • Organizer
      第86回日本細菌学会総会
    • Place of Presentation
      千葉
    • Related Report
      2013 Final Research Report
  • [Presentation] ClpXPプロテアーゼによるアダプタータンパク質を介したFlhD_4C_2認識・分解機構2013

    • Author(s)
      高屋明子
    • Organizer
      第86回日本細菌学会総会
    • Place of Presentation
      千葉
    • Related Report
      2013 Final Research Report
  • [Presentation] 協調的認識により調節されるAAA^+プロテアーゼClpXPの基質特異性2013

    • Author(s)
      佐藤慶治
    • Organizer
      第86回日本細菌学会総会
    • Place of Presentation
      千葉
    • Related Report
      2013 Final Research Report
  • [Presentation] CspC/CspEによるサルモネラの感染初期マクロファージ殺菌回避機構2013

    • Author(s)
      前田侑也
    • Organizer
      第86回日本細菌学会総会
    • Place of Presentation
      千葉
    • Related Report
      2013 Final Research Report
  • [Presentation] RlmA^<II>不活化に夜肺炎球菌のテリスロマイシン耐性化機構2013

    • Author(s)
      庄司竜麻
    • Organizer
      第86回日本細菌学会総会
    • Place of Presentation
      千葉
    • Related Report
      2013 Final Research Report
  • [Presentation] FliT fine-tunes the flagellar biogenesis by enhancing the ClpXP-catalyzed degradation of master regulator FlhD4C22013

    • Author(s)
      Yoshiharu Sato, Akiko Takaya, Tomoko Yamamoto
    • Organizer
      EMBO workshop on AAA+ proteins: from mechanism and disease to targets.
    • Place of Presentation
      Neuss, Germany
    • Related Report
      2013 Annual Research Report
  • [Presentation] Control of inflammatory response and macrophage cell death by Salmonella2012

    • Author(s)
      Takaya A
    • Organizer
      Rudbeck Life Science Symposium 2nd Chiba-Uppsala Meeting
    • Place of Presentation
      Uppsala University, Sweden
    • Year and Date
      2012-02-16
    • Related Report
      2013 Final Research Report
    • Invited
  • [Presentation] Control of inflammatory response and macrophage cell death by Salmonella2012

    • Author(s)
      Takaya A
    • Organizer
      Rudbeck Life Science Symposium '2^<nd> Chiba-Uppsala Meeting'
    • Place of Presentation
      Uppsala University, Sweden(招待講演)
    • Year and Date
      2012-02-16
    • Related Report
      2011 Annual Research Report
  • [Presentation] サルモネラYdiVの2つの機能によるべん毛マスターレギュレーターFlhD_4C_2活性制御2012

    • Author(s)
      高屋明子
    • Organizer
      第95回日本細菌学会関東支部総会
    • Place of Presentation
      東京
    • Related Report
      2013 Final Research Report
  • [Presentation] Identification of Salmonella novel effectors by bioinformatic approach2012

    • Author(s)
      Takaya A
    • Organizer
      The 11th Korea-Japan International Symposium on Mcrobiology
    • Place of Presentation
      Korea
    • Related Report
      2013 Final Research Report
    • Invited
  • [Presentation] Identification of Salmonella novel effectors by bioinformatic approach2012

    • Author(s)
      Akiko Takaya
    • Organizer
      The 11th Korea-Japan International Symposium on Microbiology
    • Place of Presentation
      Buyeo, Korea
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] サルモネラYdiVの2つの機能によるべん毛マスターレギュレーターFlhD4C2活性制御2012

    • Author(s)
      高屋明子
    • Organizer
      第95回日本細菌学会関東支部総会
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
  • [Presentation] Control of functions mediated by Salmonella Pathogenicity Island 1 by AAA^+ proteases2011

    • Author(s)
      Takaya A
    • Organizer
      Singapore-Japan Joint Forum 'Emerging Conceptsin Microbiology
    • Place of Presentation
      Notional University of Singapore, Singapore
    • Year and Date
      2011-11-15
    • Related Report
      2013 Final Research Report
    • Invited
  • [Presentation] Control of functions mediated by Salmonella Pathogenicity Island 1 by AAA^+ proteases2011

    • Author(s)
      Takaya A., Sato Y., Yamamoto T
    • Organizer
      Singapore-Japan Joint Forum 'Emerging Conceptsin Microbiology'
    • Place of Presentation
      Notional University of Singapore, Singapore(招待講演)
    • Year and Date
      2011-11-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] YdiV is a novel adaptor protein for ClpXP protease2011

    • Author(s)
      Takaya A
    • Organizer
      9th International Conference on AAA proteins
    • Place of Presentation
      Kumamoto City International Center, Japan
    • Year and Date
      2011-11-08
    • Related Report
      2013 Final Research Report
  • [Presentation] YdiV is a novel adaptor protein for ClpXP protease2011

    • Author(s)
      Takaya A., Sato Y., Yamamoto T
    • Organizer
      9^<th> International Conference on AAA proteins
    • Place of Presentation
      Kumamoto City International Center, Japan
    • Year and Date
      2011-11-08
    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.p.chiba-u.ac.jp/lab/bisei/

    • Related Report
      2013 Final Research Report
  • [Remarks] 千葉大院薬・微生物薬品化学研究室ホームページ

    • URL

      http://www.p.chiba-u.ac.jp/lab/bisei/

    • Related Report
      2013 Annual Research Report

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Published: 2013-05-15   Modified: 2019-07-29  

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