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2011 Fiscal Year Final Research Report

Elucidation of Shiga-toxigenic Escherichia coli produced Subtilase cytotoxin-induced cell damage mechanism.

Research Project

  • PDF
Project/Area Number 21390127
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Bacteriology (including Mycology)
Research InstitutionChiba University

Principal Investigator

NODA Masatoshi  千葉大学, 大学院・医学研究院, 教授 (60164703)

Co-Investigator(Kenkyū-buntansha) MORINAGA Naoko  千葉大学, 大学院・医学研究院, 准教授 (20092108)
SHIMIZU Takeshi  千葉大学, 大学院・医学研究院, 准教授 (70312840)
YAHIRO Kinnosuke  千葉大学, 大学院・医学研究院, 特任准教授 (80345024)
TSUTSUKI Hiroyasu  千葉大学, 大学院・医学研究院, 助教 (40586608)
Co-Investigator(Renkei-kenkyūsha) KUWABARA Satoshi  千葉大学, 大学院・医学研究院, 教授 (70282481)
MORI Masahiro  千葉大学, 大学院・医学研究院, 助教 (70345023)
Project Period (FY) 2009 – 2011
Keywords毒素 / ER ストレス / アポトーシス / 受容体
Research Abstract

Subtilase cytotoxin (SubAB) is an AB5 cytotoxin produced by some strains of Shiga-toxigenic Escherichia coli. The A subunit is a subtilase-like serine protease and cleaves an endoplasmic reticulum (ER) chaperone, BiP, leading to ER stress, which induces transient inhibition of protein synthesis and cell cycle arrest at G1 phase, and PERK-mediated Bax/Bak conformational change, cytochrome c release from mitochondria, followed by caspase-dependent apoptosis in mammalian cells. In addition, we showed in mice that SubAB induced small bowel hemorrhage and a coagulopathy characterized by thrombocytopenia, prolonged prothrombin time and activated partial thromboplastin time.

  • Research Products

    (32 results)

All 2012 2011 2010 2009 Other

All Journal Article (7 results) (of which Peer Reviewed: 5 results) Presentation (25 results)

  • [Journal Article] Regulation of Subtilase cytotoxin (SubAB)-induced cell death by a PKR-like endoplasmic reticulum kinase (PERK)-dependent proteasome pathway in HeLa cells2012

    • Author(s)
      Yahiro, K., H. Tsutsuki, K. Ogura, S. Nagasawa, J. Moss, M. Noda
    • Journal Title

      Infect Immun. In press

    • Peer Reviewed
  • [Journal Article] Moss, and M. Noda. 2011. Identification of Subtilase cytotoxin (SubAB) receptors whose signaling, in association with SubAB-induced BiP cleavage, is responsible for apoptosis in HeLa cells2011

    • Author(s)
      Yahiro, K., M. Satoh, N. Morinaga, H. Tsutsuki, K. Ogura, S. Nagasawa, F. Nomura, J
    • Journal Title

      Infect Immun

      Volume: 79 Pages: 617-627

    • Peer Reviewed
  • [Journal Article] Fatal hemorrhage induced by subtilase cytotoxin from Shiga-toxigenic Escherichia coli2011

    • Author(s)
      Furukawa, T., K. Yahiro, A. B. Tsuji, Y. Terasaki, N. Morinaga, M. Miyazaki, Y. Fukuda, T. Saga, J. Moss, M. Noda
    • Journal Title

      Microb Pathog

      Volume: 50 Pages: 159-167

    • Peer Reviewed
  • [Journal Article] Subtilase cytotoxin induces apoptosis in HeLa cells by mitochondrial permeabilization via activation of Bax/Bak, independent of C/EBF-homologue protein (CHOP), Ire1alpha or JNK signaling2010

    • Author(s)
      Yahiro, K., N. Morinaga, J. Moss, M. Noda
    • Journal Title

      Microb Pathog

      Volume: 49 Pages: 153-163

    • Peer Reviewed
  • [Journal Article] Purification and characterization of bacterial cytotoxin receptors2010

    • Author(s)
      Yahiro, K
    • Journal Title

      Nippon Saikingaku Zasshi

      Volume: 65 Pages: 325-31

  • [Journal Article] Novel subtilase cytotoxin produced by Shiga-toxigenic Escherichia coli induces apoptosis in Vero cells via mitochondrial membrane damage2009

    • Author(s)
      Matsuura, G., N. Morinaga, K. Yahiro, R. Komine, J. Moss, H. Yoshida, M. Noda
    • Journal Title

      Infect Immun

      Volume: 77 Pages: 2919-2924

  • [Journal Article] Characterization of cholix toxin-induced apoptosis in hela cells

    • Author(s)
      Ogura, K., K. Yahiro, H. Tsutsuki, S. Nagasawa, S. Yamasaki, J. Moss, M. Noda
    • Journal Title

      J Biol Chem

      Volume: 286 Pages: 37207-37215

    • Peer Reviewed
  • [Presentation] Fetal hemorrhage in mice induced by Subtilase cytotoxin of Shiga-toxigenic Escherichia coli2012

    • Author(s)
      野田公俊
    • Organizer
      第85回日本細菌学会総会
    • Place of Presentation
      長崎
    • Year and Date
      2012-03-27
  • [Presentation] NO biosensor plasmid for investigating2012

    • Author(s)
      清水健, 津々木博康, 野田公俊
    • Organizer
      NO levels within macrophages during bacterial infection
    • Place of Presentation
      長崎
    • Year and Date
      2012-03-27
  • [Presentation] Molecular mechanism of inhibitory effect of2012

    • Author(s)
      津々木博康, 八尋錦之助, 清水健, 野田公俊
    • Organizer
      SubAB on nitric oxide production by macrophages
    • Place of Presentation
      長崎
    • Year and Date
      2012-03-27
  • [Presentation] SubAB-induced apoptosis is regulated by a PERK-dependent proteasome pathway in HeLa cells2012

    • Author(s)
      八尋錦之助, 津々木博康, 小倉康平, 永澤明佳, 盛永直子, 野田公俊
    • Place of Presentation
      長崎
    • Year and Date
      2012-03-27
  • [Presentation] Diversity in the mechanism of human cell death caused by ADP-ribosyltransferase Cholix toxin2012

    • Author(s)
      小倉康平, 八尋錦之助, 山崎伸二, 野田公俊
    • Organizer
      第85回日本細菌学会総会
    • Place of Presentation
      長崎
    • Year and Date
      2012-03-27
  • [Presentation] 腸管出血性大腸菌が産生するSubtilase cytotoxinはマクロファージのNO産生を抑制する2011

    • Author(s)
      津々木博康, 八尋錦之助, 清水健, 野田公俊
    • Organizer
      第96回日本細菌学会関東支部総会
    • Place of Presentation
      東京
    • Year and Date
      2011-10-06
  • [Presentation] Characterization of Subtilase cytotoxin-induced apoptotic signaling pathway in HeLa cells2011

    • Author(s)
      八尋錦之助, 盛永直子, 野田公俊
    • Organizer
      International Union of Microbiological Societies
    • Place of Presentation
      北海道
    • Year and Date
      2011-09-10
  • [Presentation] The nitric oxide reductase of Enterohemorrahgicreductase of Enterohemorrahgic2011

    • Author(s)
      清水健, 津々木博康, 野田公俊
    • Organizer
      Escherichia coli plays an important role for the survival within macrophages
    • Place of Presentation
      北海道
    • Year and Date
      2011-09-10
  • [Presentation] Subtilase cytotoxin inhibits the production of nitric oxide from macrophage2011

    • Author(s)
      津々木博康, 八尋錦之助, 清水健, 野田公俊
    • Place of Presentation
      北海道
    • Year and Date
      2011-09-10
  • [Presentation] Apoptotic signaling pathways in HeLa cells induced by Cholix toxin of Vibrio cholerae2011

    • Author(s)
      小倉康平, 八尋錦之助, 山崎伸二, 野田公俊
    • Organizer
      nternational Union of Microbiological Societies 2011 Congress
    • Place of Presentation
      北海道
    • Year and Date
      2011-09-10
  • [Presentation] コレラ菌由来のADP-リボシルトランスフェラーゼ活性を有するCholix toxinが引き起こすアポトーシスシグナル伝達機構の解析2011

    • Author(s)
      小倉康平, 八尋錦之助, 山崎伸二, 野田公俊
    • Organizer
      第58回トキシンシンポジウム
    • Year and Date
      2011-07-06
  • [Presentation] 腸管出血性大腸菌の産生するSubtilase cytotoxin(SubAB)の細胞内侵入機序の解析2011

    • Author(s)
      永澤明佳, 八尋錦之助, 茂谷久子, 岩瀬博太郎, 野田公俊
    • Organizer
      第58回トキシンシンポジウム
    • Place of Presentation
      順天堂大学(東京)
    • Year and Date
      2011-07-06
  • [Presentation] 腸管出血性大腸菌の産生する新規SubABトキシンによるNO産生抑制機構の解明2011

    • Author(s)
      津々木博康, 八尋錦之助, 清水健, 野田公俊
    • Organizer
      第58回トキシンシンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2011-07-06
  • [Presentation] 腸管出血性大腸菌の産生するSubABのマウスにおける病態発現解析2011

    • Author(s)
      八尋錦之助, 古川健, 寺崎泰弘, 辻厚至, 盛永直子, 野田公俊
    • Organizer
      第58回トキシンシンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2011-07-06
  • [Presentation] 腸管出血性大腸菌 NO reductaseは志賀毒素2の産生を増加させる2011

    • Author(s)
      清水健, 津々木博康, 野田公俊
    • Organizer
      第58回トキシンシンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2011-07-06
  • [Presentation] Identification of SubAB receptor and its signaling pathway associated with BiP cleavage leading to apoptosis2010

    • Author(s)
      八尋錦之助, 盛永直子, 野田公俊
    • Organizer
      45th US-Japan Cholera and Other Baceterial Enteric Infections Joint Panel Meeting
    • Place of Presentation
      京都
    • Year and Date
      20101206-08
  • [Presentation] 腸管出血性大腸菌の産生する Subtilase cytotoxin (SubAB)の毒性発現機序の解析2010

    • Author(s)
      八尋錦之助, 盛永直子, 野田公俊
    • Organizer
      第57回トキシンシンポジウム
    • Place of Presentation
      滋賀
    • Year and Date
      20100714-16
  • [Presentation] Subtilase cytotoxin induces activation of Bax/Bak, leading to cytochrome c release and apoptosis2010

    • Author(s)
      盛永直子, 八尋錦之助, 野田公俊
    • Organizer
      第83回日本細菌学会
    • Place of Presentation
      横浜
    • Year and Date
      20100327-29
  • [Presentation] Identification of Subtilase cytotoxin receptors in HeLa cells2010

    • Author(s)
      八尋錦之助, 盛永直子, 野田公俊
    • Organizer
      第83回日本細菌学会
    • Place of Presentation
      横浜
    • Year and Date
      20100327-29
  • [Presentation] Adherence of EHEC to Caco-2 cells induces the increase of Stx1 production2010

    • Author(s)
      清水健, 野田公俊
    • Organizer
      第83回日本細菌学会
    • Place of Presentation
      横浜
    • Year and Date
      20100327-29
  • [Presentation] コレラ菌由来の新規外毒素が示す標的細胞致死活性2010

    • Author(s)
      小倉康平, 八尋錦之助, 野田公俊
    • Organizer
      インターラボセミナー
    • Place of Presentation
      千葉
    • Year and Date
      2010-12-11
  • [Presentation] 腸管出血性大腸菌の産生する新規SubABトキシンによるNO産生抑制機構の解明2010

    • Author(s)
      津々木博康, 八尋錦之助, 清水健, 野田公俊
    • Organizer
      インターラボセミナー
    • Place of Presentation
      千葉
    • Year and Date
      2010-12-11
  • [Presentation] ubtilase cytotoxin induced apoptosis in HeLa cells via mitochondrial membrane damage2009

    • Author(s)
      八尋錦之助, 盛永直子, 野田公俊
    • Organizer
      44th US-Japan Cholera and Other Bacterial Enteric Infections Joint Panel Meeting
    • Place of Presentation
      サンディエゴ、USA
    • Year and Date
      20091012-14
  • [Presentation] Effect of phage-inducing agent on the number of Stx2-expressed cells in Shiga toxin-producing Escherichia coli2009

    • Author(s)
      清水健, 野田公俊
    • Organizer
      44th US-Japan Cholera and Other Bacterial Enteric Infections Joint Panel Meeting
    • Place of Presentation
      サンディエゴ、USA
    • Year and Date
      20091012-14
  • [Presentation] プロテオーム解析による細菌毒素宿主受容体の同定と性状解析2009

    • Author(s)
      八尋錦之助, 盛永直子, 野田公俊
    • Organizer
      第6回千葉疾患プロテオミクス研究会
    • Place of Presentation
      千葉県
    • Year and Date
      2009-12-06

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Published: 2013-07-31  

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