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Protective immunity against group Astreptococcus infection following immunization with fibronectin-binding proteins

Research Project

Project/Area Number 18390489
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Morphological basic dentistry
Research InstitutionOsaka University

Principal Investigator

KAWABATA Shigetada  Osaka University, Department of Oral and Molecular Microbiology, Professor (50273694)

Co-Investigator(Kenkyū-buntansha) TERAO Yutaka  Osaka University, Department of Oral and Molecular Microbiology, Associate Professor (50397717)
NEKATA Masanobu  Osaka University, Depoartment of Oral and Molecular Miaobiology, Assistant Professor (90444497)
SUMITOMO Tomoko  Osaka University, Department of Oral and Molecular Microbiology, Assistant Professor (50423421)
OKAMOTO Shigefumi  National Institute of Biomedical Innovation, Division of Biomedical Research, Researcher (50311759)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥16,940,000 (Direct Cost: ¥15,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2007: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2006: ¥12,000,000 (Direct Cost: ¥12,000,000)
KeywordsStreptococcus pyogenes / fibronectin-binding protein / FbaA / FbaB / group A streptococci / vaccine / cell-associated protein / potective antigen / フィブロネクチン結合タンパク / 菌体表層タンパク
Research Abstract

Background. Surface-associated fibronectin (Fn) -binding proteins of group A Streptococcus pyogenes play important roles in the bacterial invasion of epithelial cells. The aim of this study was to examine the functional domain and protective antigenicity of the Fn-binding proteins FbaA and FbaB.
Methods. To investigate the functional domain of FbaA or FbaB and their localization on S. pyogenes, a series of recombinant GST-truncated FbaA or FbaB proteins were employed for immunofluorescent microscopy, ligand blot, and Biacore analyses. Mice were immunized with the truncated proteins to determine the immunogenic domains that contribute to protection against S. pyogenes infection.
Results. Ligand blot and Biacore analyses revealed that the FbaA fragments harboring a proline-rich repeat domain (RD), but not the N- and C-terminal regions, possessed Fn-binding activity. Immunofluorescent microscopy findings showed that the N-terminus and RD were exposed to external regions, suggesting that the RD serves as an Fn-binding element on live organisms. Specific antibodies were efficiently induced in N-terminus- and RD-immunized mice and demonstrated bactericidal activity against S. pyogenes in vitro. FbaA-immunized mice survived significantly longer as compared to the GST-immunized group following infection with M1 and M49 strains expressing FbaA. In addition, FbaB-immunized mice also survived longer than control mice after challenge with M3 strain expressing FbaB.
Conclusion. The Fn-binding proteins, FbaA and FbaB, are potential vaccine candidates for S. pyogenes infection.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (50 results)

All 2008 2007 2006 2005 Other

All Journal Article (27 results) (of which Peer Reviewed: 14 results) Presentation (15 results) Book (6 results) Remarks (2 results)

  • [Journal Article] Group A streptococcal cysteine protease degrades C3(C3b)and contributes to evasion of innate immunity.2008

    • Author(s)
      Terao, Y., Mori, Y., Yamaguchi, M., Shimizu, Y., Ooe, K., Hamada, S. Kawabata, S.
    • Journal Title

      Journal of Biological Chemistry 283

      Pages: 6253-6260

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Molecular and biological characterization of histidine triad protein in group A streptococci.2008

    • Author(s)
      Kunitomo, E., Terao, Y., Okamoto, S., Rikimaru, T., Hamada, S., Kawabata, S.
    • Journal Title

      Microbes and Infections 10

      Pages: 414-423

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Streptococcal immunoglobulin-binding protein Sib35 exerts stimulatory and mitogenic effects toward mouse B lymphocytes.2008

    • Author(s)
      Okamoto, S., Terao, Y., Tamura, Y., Hamada, S., Kawabata, S.
    • Journal Title

      FEMS Microbiolgy Letters 281

      Pages: 73-80

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] The Streptococcus pyogenes serotype M49 Nra-Ralp3 transcriptional regulatory network and its control of virulence factor expression from the novel eno ralp3 epf sagA pathogenicity region2008

    • Author(s)
      Kreikemeyer, B., Nakata, M., Miller, T., Hildisch, H., Kourakos, V., Standar, K., Kawabata, S., Glocker, M. 0., Podbielski, A
    • Journal Title

      Infection and Immunity 75

      Pages: 5698-5710

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] 「研究成果報告書概要(欧文)」より2008

    • Author(s)
      Terao, Y., Mori, Y., Yamaguchi, M., Shimizu, Y., Ooe, K., Hamada, S., Kawabata, S
    • Journal Title

      The Journal of Biological Chemistry 283

      Pages: 6253-6260

    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Molecular and biological characterization of histidine triad protein in group A streptococci2008

    • Author(s)
      Kunitomo, E., Terao, Y., Okamoto, S., Rikimaru, T., Hamada, S., Kawabata, S
    • Journal Title

      Microbes and Infection 10

      Pages: 414-423

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Group A streptococcal cysteine protease degrades C3 (C3b) and contributes to evasion of innate immunity.2008

    • Author(s)
      Terao, Y., Mori, Y., Yamaguchi, M., Shimizu, Y., Ooe, K., Hamada, S. and Kawabata S.
    • Journal Title

      Journal of Biological Chemistry (印刷中)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular and biological characterization of histidine triad protein in group A streptococci.2008

    • Author(s)
      Kunitomo, E., Terao, Y., Okamoto, S., Rikimaru, T., Hamada, S., Kawabata, S.
    • Journal Title

      Microbes and Infections (印刷中)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Streptococcal immunoglobulin-binding protein Sib35 exerts stimulatory and mitogenic effects toward mouse B lymphocytes.2008

    • Author(s)
      Okamoto, S., Terao, Y., Tamura, Y., Hamada, S., Kawabata, S.
    • Journal Title

      FEMS Microbiolgy Letters (印刷中)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Induction of immune responses by streptococcal water-insoluble α-glucans.2007

    • Author(s)
      Okamaoto, S., Terao, Y., Kaminishi, H., Hamada, S., Kawabata, S.
    • Journal Title

      Journal of Dental Research 86

      Pages: 242-248

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Calcineurin potentiates the activation of procaspase-3 by accelerating its proteolytic maturation.2007

    • Author(s)
      Saeki, M., Irie, Y. Ni, L. Itsuki, Y. Terao, Y., Kawabata, S., Kamisaki, Y.
    • Journal Title

      Journal of Biological Chemistry 282

      Pages: 11786-11794

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] The Streptococcus pyogenes serotype M49 Nra-Ralp3 transcriptional regulatory network and its control of virulence factor expression from the novel eno ralp3 epf sagA pathogenicity region.2007

    • Author(s)
      Kreikemeyer, B., Nakata, M., Koller, T., Hildisch, H., Kourakos, V., Standar, K., Kawabata, S., Glocker, M. O. Podbielski, A.
    • Journal Title

      Infection and Immunity 75

      Pages: 5698-5710

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Induction of immune responses by streptococcal water-insoluble a-glucans2007

    • Author(s)
      Okamaoto, S., Terao, Y., Kaminishi, H., Hamada, S., Kawabata S
    • Journal Title

      Journal of Dental Research 86

      Pages: 242-248

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Calcineurin potentiates the activation of procaspase-3 by accelerating its proteolytic maturation2007

    • Author(s)
      Saeki, M., Irie, Y., Ni, L., Itsuki, Y., Terao, Y., Kawabata, S., Kamisaki, Y
    • Journal Title

      The Journal of Biological Chemistry 282

      Pages: 11786-11794

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Induction of immune responses by streptococcal water-insoluble α-glucans.2007

    • Author(s)
      Okamaoto, S., Terao, Y., Kaminishi, H., Hamada, S., Kawabata S.
    • Journal Title

      Journal of Dental Research 86

      Pages: 242-248

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Calcineurin potentiates the activation of procaspase-3 by accelerating its proteolytic maturation.2007

    • Author(s)
      Saeki, M., Irie, Y. Ni, L. Itsuki, Y. Terao, Y., Kawabata, S., Kamisaki Y.
    • Journal Title

      Journal of Biological Chemistry 282

      Pages: 11786-11794

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Streptococcus pyogenes serotype M49 Nra-Ralp3 transcriptional regulatory network and its control of virulence factor expression from the novel eno ralp3 epf sagA pathogenicity region.2007

    • Author(s)
      Kreikemeyer, B., Nakata, M., Koller, T., Hildisch, H., Kourakos, V., Standar, K., Kawabata, S., Glocker, M.O. and Podbielski, A.
    • Journal Title

      Infection and Immunity 75

      Pages: 5698-5710

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inflammatory immune responses by water-insoluble α-glucans2007

    • Author(s)
      Okamoto, S., Y.Terao, H.Kaminishi, S.Hamada, S.Kawabata
    • Journal Title

      Journal of Dental Research 86・3

      Pages: 242-248

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 劇症型A群レンサ球菌感染症(劇症化の分子機構)2007

    • Author(s)
      川端重忠, 寺尾 豊
    • Journal Title

      BIO Clinica 22・2

      Pages: 39-44

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Multifunctional glyceraldehyde-3-phosphate dehydrogenase of Streptococcus pyogenes is essential for evasion from neutrophils.2006

    • Author(s)
      Terao, Y., Yamaguchi, M., Hamada, S., Kawabata, S.
    • Journal Title

      The Journal of Biological Chemistry 281

      Pages: 14215-14223

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Role of Streptococcus sanguinis sortase A in bacterial colonization.2006

    • Author(s)
      Yamaguchi, M., Terao, Y., Ogawa, T., Takahashi, T., Hamada, S., Kawabata, S.
    • Journal Title

      Microbes and Infection 8

      Pages: 2791-2796

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Multifunctional glyceraldehyde-3-phosphate dehydrogenase of Streptococcus pyogenes is essential for evasion from neutrophils2006

    • Author(s)
      Terao, Y., Yamaguchi, M., Hamada, S., Kawabata, S
    • Journal Title

      The Journal of Biological Chemistry 281

      Pages: 14215-14223

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Role of Streptococcus sanguinis sortase A in bacterial colonization2006

    • Author(s)
      Yamaguchi, M., Terao, Y., Ogawa, T., Takahashi, T., Hamada, S., Kawabata, S
    • Journal Title

      Microbes and Infection 8

      Pages: 2791-2796

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Multifunctional glyceraldehyde-3-phosphate dehydrogenase of Streptococcus pyogenes is essential for evasion from neutrophils2006

    • Author(s)
      Terao, Y., M.Yamaguchi, S.Hamada, S.Kawabata
    • Journal Title

      The Journal of Biological Chemistry 281・20

      Pages: 14215-14223

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Role of Streptococcus sanguinis sortase A in bacterial colonization2006

    • Author(s)
      Yamaguchi, M., Y.Terao, T.Ogawa, T.Takahashi, S.Hamada, S.Kawabata
    • Journal Title

      Microbes and Infection 8

      Pages: 2791-2796

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 劇症型A群レンサ球菌感染症2006

    • Author(s)
      寺尾 豊, 川端重忠
    • Journal Title

      Pharma Medica 24・8

      Pages: 43-46

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Streptococcal immunoglobulin-binding protein Sib35 exerts stimulatory and mitogenic effects toward mouse B lymphocytes2005

    • Author(s)
      Okamoto, S., Terao, Y., Tamura, Y., Hamada, S., Kawabata, S
    • Journal Title

      FEMS Microbiology Letters 281

      Pages: 73-80

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] A群レンサ球菌線毛の機能検索と発現機構の解析2008

    • Author(s)
      中田匡宣, 住友倫子, 寺尾 豊, 川端重忠
    • Organizer
      第6回感染症沖縄フォーラム
    • Place of Presentation
      沖縄県中頭郡
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] SpeBによるA群レンサ球菌感染症の重症化機構の解析2008

    • Author(s)
      寺尾 豊, 山口雅也, 森 有可, 浜田茂幸, 川端重忠
    • Organizer
      第81回日本細菌学会総会
    • Place of Presentation
      京都市
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] A群レンサ球菌線毛の機能解析2008

    • Author(s)
      中田匡宣, 住友倫子, 寺尾 豊, 川端重忠
    • Organizer
      第81回日本細菌学会総会
    • Place of Presentation
      京都市
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Streptococcus pneumoniaeにおけるプラスミン活性獲得機構の解析2008

    • Author(s)
      山口雅也, 寺尾 豊, 森 有可, 浜田茂幸, 川端重忠
    • Organizer
      第81回日本細菌学会総会
    • Place of Presentation
      京都市
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Streptococcus pneumoniae感染における好中球の浸潤と組織侵入機構の検索2008

    • Author(s)
      森 有可, 山口雅也, 寺尾 豊, 浜田茂幸, 川端重忠
    • Organizer
      第81回日本細菌学会総会
    • Place of Presentation
      京都市
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Streptococcus sanguinisのSortase Aは歯面付着性および抗貪食能に関与する2007

    • Author(s)
      山口雅也, 寺尾 豊, 森 有可, 浜田茂幸, 川端重忠
    • Organizer
      大阪大学歯学会第105回例会
    • Place of Presentation
      吹田市
    • Year and Date
      2007-11-22
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] A群レンサ球菌pilus発現機構の解析2007

    • Author(s)
      中田 匡宣, 住友 倫子, 寺尾 豊, 川端 重忠
    • Organizer
      第60回日本細菌学会関西支部総会
    • Place of Presentation
      吹田市
    • Year and Date
      2007-11-10
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Streptococcus pneumoniaeに対するキメラ免疫グロブリン製剤の構築2007

    • Author(s)
      寺尾 豊, 山口雅也, 中田匡宣, 浜田茂幸, 川端重忠
    • Organizer
      第49回歯科基礎医学会学術大会
    • Place of Presentation
      札幌市
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] A群レンサ球菌のプロテアーゼ依存性の補体免疫回避機構2007

    • Author(s)
      寺尾 豊, 川端重忠
    • Organizer
      第50回日本感染症学会中日本地方会学術集会
    • Place of Presentation
      神戸市
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Plasmin(ogen)-and fibronectin-binding protein of Streptococcus pneumoniae provides bacterial plasmin activity2007

    • Author(s)
      Yamaguchi, M., Terao, Y., Mori, Y., Hamada, S., Kawabata, S.
    • Organizer
      107th General Meeting American Society for Microbiology
    • Place of Presentation
      Toronto, Canada
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Role of Streptococcus pyogenes FCT-region sortase and other components in pilus assembly and virulence.2007

    • Author(s)
      Nakata, M., Ribardo, D. A., Mclver, K. S., Kawabata, S., Podbielski, A., Kreikemeyer, B.
    • Organizer
      107th General Meeting American Society for Microbiology
    • Place of Presentation
      Toronto, Canada
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Plasmin(ogen)- and fibronectin-binding protein of Streptococcus pneumoniae provides bacterial plasmin activity2007

    • Author(s)
      Yamaguchi, M., Terao, Y., Mori, V., Hamada, S., Kawabata, S
    • Organizer
      107th General Meeting American Society for Microbiology
    • Place of Presentation
      Toronto, Canada
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Role of Streptococcus pyogenes FCT-region sortase and other components in pilus assembly and virulence2007

    • Author(s)
      Nakata, M., Ribardo, D.A., Mclver, K.S., Kawabata, S., Podbielski, A., Kreikemeyer, B
    • Organizer
      107th General Meeting American Society for Microbiology
    • Place of Presentation
      Toronto, Canada
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Multifunctional glyceraldehyde-3-phosphate dehydrogenase of Streptococcus pyogenes is essential for evasion fom neutrophils2006

    • Author(s)
      Kawabata S., Terao Y., Yamaguchi M., Hamada S.
    • Organizer
      2nd FEMS Congress of European Microbiology
    • Place of Presentation
      Madrid, Spain
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Multifunctional glyceraldehyde-3-phosphate dehydrogenase of Streptococcus pyogenes is essential for evasion from neutrophils2006

    • Author(s)
      Kawabata, S., Terao, Y., Yamaguchi, M., Hamada, S
    • Organizer
      2nd FEMS Congress of European Microbiologists
    • Place of Presentation
      Madrid, Spain
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] BIO Clinica「劇症型A群レンサ球菌感染症(劇症化の分子機構)」2007

    • Author(s)
      川端重忠, 寺尾 豊
    • Total Pages
      6
    • Publisher
      北隆館
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Book] 化学療法の領域「レンサ球菌の新たな理解に向けて.特集 病原体の感染戦略における新たな知見」2007

    • Author(s)
      住友倫子, 川端重忠
    • Total Pages
      7
    • Publisher
      医療ジャーナル社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Book] 医学のあゆみ「A群レンサ球菌感染症のメカニズム」2007

    • Author(s)
      川端重忠, 山口雅也
    • Total Pages
      6
    • Publisher
      医歯薬出版
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Book] 炎症と疾患「レンサ球菌感染症に対する免疫療法の可能性」2007

    • Author(s)
      中田匡宣, 寺尾 豊, 川端重忠
    • Total Pages
      6
    • Publisher
      先端医学社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Book] 実験医学増刊号25「口腔感染症」2007

    • Author(s)
      寺尾 豊, 川端重忠
    • Total Pages
      6
    • Publisher
      羊土社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Book] Pharma Medica「劇症型溶血性A群レンサ球菌感染症」2006

    • Author(s)
      寺尾 豊, 川端重忠
    • Total Pages
      4
    • Publisher
      メディカルレビュー社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Remarks] 「研究成果報告書概要(和文)」より

    • URL

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

    • Related Report
      2007 Final Research Report Summary
  • [Remarks]

    • URL

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

    • Related Report
      2007 Annual Research Report

URL: 

Published: 2006-04-01   Modified: 2016-04-21  

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