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Study on the mechanism of paroxysmal coughing seen in pertussis

Research Project

Project/Area Number 17H04075
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Bacteriology (including mycology)
Research InstitutionOsaka University

Principal Investigator

Horiguchi Yasuhiko  大阪大学, 微生物病研究所, 教授 (00183939)

Co-Investigator(Kenkyū-buntansha) 杉浦 孔明  国立研究開発法人情報通信研究機構, 先進的音声翻訳研究開発推進センター先進的音声技術研究室, 主任研究員 (60470473)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2019: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2018: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2017: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Keywords百日咳菌 / 発作性咳嗽 / 動物モデル
Outline of Final Research Achievements

Whooping cough, Bordetella pertussis infection, is characterized by paroxysmal cough, the mechanism of which has not been studied because of lack of a versatile animal model reproducing the cough. In this study, we established an experimental mouse model to reproduce the coughing by B. pertussis infection. By using this model, we identified three distinct bacterial virulence factors, which were tentatively designated A, B, and C as the causative agents for the cough. When intranasally administered, purified preparations of the three factors produced coughing in mice, indicating these three factors were necessary and sufficient to cause coughing. Further analyses demonstrated that factor C triggers to evoke coughing and factor A amplifies and sustains the factor C-evoked signals. Factor B was considered to exacerbate the effect of factor C.

Academic Significance and Societal Importance of the Research Achievements

本研究の成果からマウスの咳発作に必要な百日咳菌の病原因子が3種類同定でき、それぞれの咳発作メカニズムに関わるヒエラルキーもある程度予想できるまでになった。動物の咳反射応答のメカニズムにはまだ不明な点が多いが、基本的な経路のいくつかは明らかにされつつある。これらの既知の咳反射応答の経路に百日咳菌病原因子がどのように関わるのかについては、今後の大きな研究課題である。百日咳菌病原因子の機能解析を通じた成果は、百日咳の咳発作の原因療法の解析に道を拓くほか、基礎生命科学の面から見て動物の咳反射応答の全容解明に貢献するものと期待できる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (15 results)

All 2020 2019 2018

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (8 results) (of which Int'l Joint Research: 1 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Expression of small RNAs of Bordetella pertussis colonizing murine tracheas2020

    • Author(s)
      Hiramatsu Yukihiro、Suzuki Koichiro、Motooka Daisuke、Nakamura Shota、Horiguchi Yasuhiko
    • Journal Title

      Microbiology and Immunology

      Volume: - Issue: 6 Pages: 469-475

    • DOI

      10.1111/1348-0421.12791

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bordetella Dermonecrotic Toxin Is a Neurotropic Virulence Factor That Uses CaV3.1 as the Cell Surface Receptor.2020

    • Author(s)
      Teruya S, Hiramatsu Y, Nakamura K, Fukui-Miyazaki A, Tsukamoto K, Shinoda N, Motooka D, Nakamura S, Ishigaki K, Shinzawa N, Nishida T, Sugihara F, Maeda Y, Horiguchi Y.
    • Journal Title

      mBio

      Volume: 11 Issue: 2 Pages: 03146-19

    • DOI

      10.1128/mbio.03146-19

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bordet‐Gengou agar medium supplemented with albumin‐containing biologics for cultivation of bordetellae2019

    • Author(s)
      Hiramatsu Yukihiro、Osada‐Oka Mayuko、Horiguchi Yasuhiko
    • Journal Title

      Microbiology and Immunology

      Volume: 63 Issue: 12 Pages: 513-516

    • DOI

      10.1111/1348-0421.12742

    • NAID

      40022103554

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] BspR/BtrA, an Anti-σ Factor, Regulates the Ability of Bordetella bronchiseptica To Cause Cough in Rats2019

    • Author(s)
      Nakamura Keiji、Shinoda Noriko、Hiramatsu Yukihiro、Ohnishi Shinya、Kamitani Shigeki、Ogura Yoshitoshi、Hayashi Tetsuya、Horiguchi Yasuhiko
    • Journal Title

      mSphere

      Volume: 4 Issue: 2

    • DOI

      10.1128/msphere.00093-19

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Eukaryotic Host Factor 14-3-3 Inactivates Adenylate Cyclase Toxins of Bordetella bronchiseptica and B.?parapertussis, but Not B.?pertussis2018

    • Author(s)
      Fukui-Miyazaki Aya、Toshima Hirono、Hiramatsu Yukihiro、Okada Keisuke、Nakamura Keiji、Ishigaki Keisuke、Shinzawa Naoaki、Abe Hiroyuki、Horiguchi Yasuhiko
    • Journal Title

      mBio

      Volume: 9 Issue: 4 Pages: 1-15

    • DOI

      10.1128/mbio.00628-18

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Bordetella bronchiseptica utilizes Acanthamoeba castellanii as a temporal niche2020

    • Author(s)
      Dendi Krisna Nugraha、山口博之,堀口安彦
    • Organizer
      第93回日本細菌学会総会
    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
  • [Presentation] Modification of Bordet-Gengou agar medium for cultivation of bordetellae2020

    • Author(s)
      平松征洋、岡真優子、堀口安彦
    • Organizer
      第93回日本細菌学会総会
    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
  • [Presentation] Identification of Bordetella dermonecrotic toxin recepto2019

    • Author(s)
      平松征洋、照屋志帆乃、中村佳司、福井理、塚本健太郎、堀口安彦
    • Organizer
      第18回あわじ感染と免疫国際フォーラム
    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
  • [Presentation] ボルデテラ壊死毒(DNT)の受容体同定を通じた百日咳病態の解析2019

    • Author(s)
      照屋志帆乃、平松征洋、篠田典子、塚本健太郎、中村佳司、石垣圭祐、堀口安彦
    • Organizer
      第66回トキシンシンポジウム
    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
  • [Presentation] entification of Bordetella dermonecrotic toxin receptor2019

    • Author(s)
      Shihono Teruya, Yukihiro Hiramatsu, Noriko Shinoda, Kentao Tsukamoto, Keiji Nakamura, Aya Fukui-Miyazaki, Keisuke Ishigaki, Yasuhiko Horiguchi
    • Organizer
      ETOX19
    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ボルデテラ壊死毒(DNA) の細胞受容体同定2018

    • Author(s)
      照屋志帆乃、中村佳司、石垣佳祐、新澤直明、堀口安彦
    • Organizer
      第65回トキシンシンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] 受容体同定を通じたボルデテラ壊死毒(DNT) の標的組織探索2018

    • Author(s)
      照屋志帆乃、塚本健太郎、福井理、中村佳司、石垣佳祐、新澤直明、堀口安彦
    • Organizer
      第71回日本細菌学会関西支部総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 百日咳菌のV型分泌装置Vag8の機能的解析2018

    • Author(s)
      小野田直記、平松征洋、照屋志帆乃、鈴木孝一朗、堀口安彦
    • Organizer
      第71回日本細菌学会関西支部総会
    • Related Report
      2017 Annual Research Report
  • [Patent(Industrial Property Rights)] 百日咳に対する鎮咳薬および百日咳に対する鎮咳薬のスクリーニング法2019

    • Inventor(s)
      堀口安彦、平松征洋
    • Industrial Property Rights Holder
      堀口安彦、平松征洋
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report
  • [Patent(Industrial Property Rights)] 百日咳に対する鎮咳薬および百日咳に対する鎮咳薬のスクリーニング法2019

    • Inventor(s)
      堀口安彦、平松征洋
    • Industrial Property Rights Holder
      堀口安彦、平松征洋
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Related Report
      2018 Annual Research Report

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Published: 2017-04-28   Modified: 2021-03-11  

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