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Involvement of nontoxic protein in botulinum toxin complex on digestive injury in botulism food poisoning

Research Project

Project/Area Number 15K08475
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Bacteriology (including mycology)
Research InstitutionTokyo University of Agriculture

Principal Investigator

WATANABE Toshihiro  東京農業大学, 生物産業学部, 教授 (80175695)

Co-Investigator(Renkei-kenkyūsha) SAGANE Yoshimasa  東京農業大学, 生物産業学部, 教授 (00624660)
NIWA Koichi  東京農業大学, 生物産業学部, 教授 (20301012)
MUTOH Shingo  鎌倉女子大学, 家政学部, 講師 (20749890)
SUZUKI Tomonori  東京農業大学, 生命科学部, 准教授 (90453836)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsボツリヌス食中毒 / 細胞毒性 / ボツリヌス毒素複合体 / ボツリヌス毒素 / 空胞化 / 小腸上皮細胞 / タンパク質複合体 / エンドソーム / 小腸上皮組織
Outline of Final Research Achievements

Botulinum neurotoxin (BoNT) causes muscle paralysis. Botulism food poisoning may cause gastrointestinal disorders and vascular lesions, and the cause of these symptoms is unclear. On the other hand, BoNT associates non-toxic proteins and forms a toxin complex. In this study, for the first time, we demonstrated that a nontoxic protein complex shows cytotoxicity, accompanied by formation of vacuoles within the cytoplasm, to rat small intestinal epithelial cells. In this study, furthermore, it was revealed that the nontoxic protein complex of botulinum toxin forms vacuoles within the cell by a mechanism different from other vacuolating toxins. The results of this research are expected to lead to the elucidation of the mechanism of botulism intoxication, which is still unclear.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (10 results)

All 2017 2016 Other

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 2 results) Presentation (2 results) (of which Int'l Joint Research: 2 results) Remarks (1 results)

  • [Journal Article] Building-block architecture of botulinum toxin complex: Conformational changes provide insights into the hemagglutination ability of the complex2017

    • Author(s)
      Suzuki T, Sagane Y, Matsumoto T, Hasegawa K, Yamano A, Niwa K, Watanabe T
    • Journal Title

      Biochemistry and Biophysics Reports

      Volume: 9 Pages: 67-71

    • DOI

      10.1016/j.bbrep.2016.11.008

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Reversible Association of the Hemagglutinin Subcomplex, HA-33/HA-17 Trimer, with the Botulinum Toxin Complex2017

    • Author(s)
      Sagane Y, Mutoh S, Koizumi R, Suzuki T, Miyashita S, Miyata K, Ohyama T, Niwa K, Watanabe T
    • Journal Title

      The Protein Journal

      Volume: 36 Issue: 5 Pages: 417-424

    • DOI

      10.1007/s10930-017-9733-y

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Construction of ‘‘Toxin Complex’’ in a Mutant Serotype C Strain of Clostridium botulinum Harboring a Defective Neurotoxin Gene2016

    • Author(s)
      Tomonori Suzuki, Thomas Nagano, Koichi Niwa, Masataka Uchino, Motohiro Tomizawa, Yoshimasa Sagane, and Toshihiro Watanabe
    • Journal Title

      Current Microbiology

      Volume: 74 Issue: 1 Pages: 49-54

    • DOI

      10.1007/s00284-016-1150-5

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] "Non-Toxic" Proteins of the Botulinum Toxin Complex Exert In-vivo Toxicity.2016

    • Author(s)
      Shin-Ichiro Miyashita, Yoshimasa Sagane, Tomonori Suzuki, Takashi Matsumoto, Koichi Niwa, and Toshihiro Watanabe
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1

    • DOI

      10.1038/srep31043

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Conformational divergence in the HA-33/HA-17 trimer of serotype C and D botulinum toxin complex.2016

    • Author(s)
      Yoshimasa Sagane, Shintaro Hayashi, Tomonori Akiyama, Takashi Matsumoto, Kimiko Hasegawa, Akihito Yamano, Tomonori Suzuki, Koichi Niwa, Toshihiro Watanabe, and Shunsuke Yajima
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 476 Issue: 4 Pages: 280-285

    • DOI

      10.1016/j.bbrc.2016.05.113

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Data describing inhibitory profiles of sugars against hemagglutination by the botulinum toxin complex of Clostridium botulinum serotypes C and D2016

    • Author(s)
      Yoshimasa Sagane, Minoru Ito, Keita Miyata, Tomonori Suzuki, Koichi Niwa, Suguru Oguri, and Toshihiro Watanabe
    • Journal Title

      Data in Brief

      Volume: 9 Pages: 413-416

    • DOI

      10.1016/j.dib.2016.09.014

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Isolation of botulinolysin, a thiol-activated hemolysin, from serotype D Clostridium botulinum: A species-specific gene duplication in Clostridia2016

    • Author(s)
      Tomonori Suzuki, Thomas Nagano, Koichi Niwa, Shingo Mutoh, Masataka Uchino, Motohiro Tomizawa, Yoshimasa Sagane, and Toshihiro Watanabe
    • Journal Title

      Microbiological Research

      Volume: 193 Pages: 20-29

    • DOI

      10.1016/j.micres.2016.08.011

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] Internalization and intercellular trafficking of the serotype D botulinum neurotoxin binding protein, nontoxic nonhemagglutinin, in epithelial and endothelial cells.2017

    • Author(s)
      Sagane, Y., Miyashita, S. -I., Hosoya, K., Karatsu, S., Kurihara, A., Sugawara, C., Niwa, K., Watanabe, T.
    • Organizer
      10th International Conference on the Molecular Biology and Pathogenesis of the Clostridia.
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] “Non-toxic” proteins of the botulinum toxin complex exert cytotoxicity with vacuole formation in the cell.2017

    • Author(s)
      Sagane, Y., Miyashita, S. -I., Kurihara, A., Sugawara, C., Hosoya, K., Karatsu, S., Niwa, K., Watanabe, T.
    • Organizer
      10th International Conference on the Molecular Biology and Pathogenesis of the Clostridia.
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Remarks] 無毒タンパク質が無毒でないことを発見【食品香粧学科の研究】

    • URL

      http://www.nodai.ac.jp/academics/bio/o_food/news/16800/

    • Related Report
      2016 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2019-03-29  

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