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Creation of a novel biomarker for leptospirosis using the adipose tissue colonization mechanism.

Research Project

Project/Area Number 21K16320
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 54030:Infectious disease medicine-related
Research InstitutionFukuoka University

Principal Investigator

Ozuru Ryo  福岡大学, 医学部, 講師 (70763035)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2023: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywordsレプトスピラ / レプトスピラ症 / 脂肪組織 / 脂質代謝 / バイオマーカー / 人獣共通感染症 / 脂質代謝異常症 / アディポカイン
Outline of Research at the Start

病原細菌レプトスピラが引き起こすレプトスピラ症は、ヒトでは世界で年間100万件以上発生している世界最大の人獣共通感染症の一つである。早期に発見できず重症化すると、致死的なワイル病を発症することがある。そのため、感染早期から検査可能な迅速診断キットの開発が望まれている。本申請者は先行研究において、レプトスピラは経皮感染するとまず脂肪組織の血管内に定着して増殖することを見出した。本研究では、レプトスピラの脂肪組織定着機構をレプトスピラ症バイオマーカーとして利用するため、ヒトの脂肪組織を用いた遺伝子発現解析によって菌の定着因子や宿主の防御因子を同定し、迅速診断キット開発に繋げる。

Outline of Final Research Achievements

This study aims to elucidate the mechanisms by which Leptospira establishes itself in adipose tissue and to identify novel biomarkers for leptospirosis. Using an ex vivo human subcutaneous adipose tissue infection model, we observed the secretion of multiple adipokines upon Leptospira infection, particularly those involved in inflammatory and immune responses. Additionally, in an in vivo infection model using mouse-derived preadipocyte cell line 3T3-L1, pathogenic Leptospira induced lipolysis, utilizing extracellular glycerol as a carbon source. These findings suggest new diagnostic and therapeutic approaches for leptospirosis, potentially advancing the management of this significant infectious disease.

Academic Significance and Societal Importance of the Research Achievements

本研究は、病原細菌レプトスピラが皮下脂肪組織に定着し、そこで増殖するメカニズムを一部解明しました。またこの際に、レプトスピラが脂肪組織に脂肪分解を起こすことも見出しました。この発見は、レプトスピラ症の早期診断に役立つ新たなバイオマーカーの開発に繋がる可能性があります。レプトスピラ症は、軽度の風邪様症状から重篤なワイル病に進行することがあり、早期診断と治療が非常に重要です。この研究は、社会全体にとって感染症対策の向上に寄与し、農業や畜産業の経済的損失を減少させる効果も期待されます。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (21 results)

All 2024 2023 2022 2021 Other

All Int'l Joint Research (6 results) Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (11 results) (of which Int'l Joint Research: 4 results,  Invited: 1 results)

  • [Int'l Joint Research] Monash University(オーストラリア)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] University of the Philippines Manilla(フィリピン)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] モナシュ大学(オーストラリア)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] フィリピン大学マニラ校(フィリピン)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] フィリピン大学マニラ校(フィリピン)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] モナシュ大学(オーストラリア)

    • Related Report
      2021 Research-status Report
  • [Journal Article] The appearance of anti-spike receptor binding domain immunoglobulin G4 responses after repetitive immunization with messenger RNA-based COVID-19 vaccines2024

    • Author(s)
      Yoshimura Michinobu、Sakamoto Atsuhiko、Ozuru Ryo、Kurihara Yusuke、Itoh Ryota、Ishii Kazunari、Shimizu Akinori、Chou Bin、Nabeshima Shigeki、Hiromatsu Kenji
    • Journal Title

      International Journal of Infectious Diseases

      Volume: 139 Pages: 1-5

    • DOI

      10.1016/j.ijid.2023.11.028

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Insufficient anti-spike RBD IgA responses after triple vaccination with intramuscular mRNA BNT162b2 vaccine against SARS-CoV-22024

    • Author(s)
      Yoshimura Michinobu、Sakamoto Atsuhiko、Ozuru Ryo、Kurihara Yusuke、Itoh Ryota、Ishii Kazunari、Shimizu Akinori、Chou Bin、Sechi Yusuke、Fujikane Aya、Nabeshima Shigeki、Hiromatsu Kenji
    • Journal Title

      Heliyon

      Volume: 10 Issue: 1 Pages: e23595-e23595

    • DOI

      10.1016/j.heliyon.2023.e23595

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Longitudinal Dynamics of SARS-CoV-2 IgG Antibody Responses after the Two-Dose Regimen of BNT162b2 Vaccination and the Effect of a Third Dose on Healthcare Workers in Japan2022

    • Author(s)
      Sakamoto Atsuhiko、Yoshimura Michinobu、Itoh Ryota、Ozuru Ryo、Ishii Kazunari、Sechi Yusuke、Nabeshima Shigeki、Hiromatsu Kenji
    • Journal Title

      Vaccines

      Volume: 10 Issue: 6 Pages: 830-830

    • DOI

      10.3390/vaccines10060830

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A machine learning model of microscopic agglutination test for diagnosis of leptospirosis2021

    • Author(s)
      Oyamada Yuji、Ozuru Ryo、Masuzawa Toshiyuki、Miyahara Satoshi、Nikaido Yasuhiko、Obata Fumiko、Saito Mitsumasa、Villanueva Sharon Yvette Angelina M.、Fujii Jun
    • Journal Title

      PLOS ONE

      Volume: 16 Issue: 11 Pages: e0259907-e0259907

    • DOI

      10.1371/journal.pone.0259907

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] A unique strategy for acquiring carbon sources: Leptospira induces lipolysis in the host adipocytes via adrenergic receptors.2024

    • Author(s)
      Ryo Ozuru, Yusuke Kurihara, Kazunari Ishii, Shotaro Fujiki, Michinobu Yoshimura and Kenji Hiromatsu
    • Organizer
      Gordon Research Conference 2024 Biology of Spirochetes
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Automating tests for leptospirosis with deep learning -Seeing "by computer" is believing-2024

    • Author(s)
      Ryo Ozuru
    • Organizer
      The PSM Cluster 1 Symposium with the theme “Computational Microbiology and Biotechnology in an Evolving Microbial World”
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Pathogenic Leptospira induces lipolysis in the murine adipocytes in vitro and in vivo2024

    • Author(s)
      Ryo Ozuru, Michinobu Yoshimura, Shotaro Fujiki, Kazunari Ishii, Akinori Shimizu, Yusuke Kurihara, Shuntaro Kuwahara, Kenji Hiromatsu
    • Organizer
      第97回日本細菌学会総会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Percutaneously Infected Leptospira Induces Lipolysis in the Host Adipose Tissue.2024

    • Author(s)
      Ryo Ozuru, Michinobu Yoshimura, Shotaro Fujiki, Kazunari Ishii, Akinori Shimizu, Yusuke Kurihara, Shuntaro Kuwahara, and Kenji Hiromatsu
    • Organizer
      The 13th Conference of the International Leptospirosis Society
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Pathogenic leptospires induce lipolysis in the host adipocytes via adrenergic receptors to obtain their carbon sources.2023

    • Author(s)
      Ryo Ozuru, Kazunari Ishii, Shotaro Fujiki and Kenji Hiromatsu
    • Organizer
      The 21st Awaji International Forum on Infection and Immunity
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 機械学習による感染症検査の自動化・標準化2023

    • Author(s)
      尾鶴亮
    • Organizer
      第17回細菌学若手コロッセウム
    • Related Report
      2023 Annual Research Report
  • [Presentation] アドレナリン受容体を介したレプトスピラの宿主脂質分解2023

    • Author(s)
      尾鶴 亮、石井 一成、栗原 悠介、藤木 正太郎、吉村 芳修、廣松 賢治
    • Organizer
      第59回レプトスピラ・シンポジウム
    • Related Report
      2023 Annual Research Report
  • [Presentation] レプトスピラ感染による宿主の脂質代謝変化2022

    • Author(s)
      尾鶴 亮、石井 一成、廣松 賢治
    • Organizer
      第58回レプトスピラシンポジウム
    • Related Report
      2022 Research-status Report 2021 Research-status Report
  • [Presentation] 病原性レプトスピラ感染による宿主の免疫応答と脂質代謝変化2022

    • Author(s)
      尾鶴 亮、石井 一成、廣松 賢治
    • Organizer
      第16回細菌学若手コロッセウム
    • Related Report
      2022 Research-status Report
  • [Presentation] PATHOGENIC LEPTOSPIRES INDUCE LIPOLYSIS IN HOST ADIPOCYTES TO OBTAIN THEIR CARBON SOURCES.2022

    • Author(s)
      Ryo Ozuru, Michinobu Yoshimura, Yusuke Kurihara, Kazunari Ishii, Kenji Hiromatsu
    • Organizer
      12th International Leptospirosis Society Conference 2022
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] 凝集反応検査を自動化する-レプトスピラ症における顕微鏡下凝集試験の深層学習判定モデルを基に-2021

    • Author(s)
      尾鶴 亮、中野 里咲、小山田 雄仁
    • Organizer
      第95回日本細菌学会総会
    • Related Report
      2021 Research-status Report

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Published: 2021-04-28   Modified: 2025-01-30  

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