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Elucidation of the mechanism of evasion of the host immune response by the causative bacteria of Edwardsiellosis in fishes - From the viewpoint of reactive oxygen generation system -

Research Project

Project/Area Number 20K06228
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 40040:Aquatic life science-related
Research InstitutionNagasaki University

Principal Investigator

OSATOMI Kiyoshi  長崎大学, 水産・環境科学総合研究科(水産), 教授 (40253702)

Co-Investigator(Kenkyū-buntansha) 平坂 勝也  長崎大学, 海洋未来イノベーション機構, 准教授 (70432747)
吉田 朝美  長崎大学, 水産・環境科学総合研究科(水産), 准教授 (80589870)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords活性酸素生成系 / 酸化ストレス / プロモーター / 転写制御因子 / 魚病細菌 / flagellin / 細胞培養系 / 免疫応答 / 培養細胞系 / Edwardsiella tarda
Outline of Research at the Start

魚類エドワジエラ症の原因菌Edwardssiella tarda (E. tarda) は、マクロファージに貪食された後も細胞内増殖能を有し、活性酸素種 (ROS) 依存的殺菌機構を回避している。そこで本研究では、鞭毛構成タンパク質flagellinに着目し、主にマクロファージ培養細胞系を用いて、E.tarda強毒株flagellinによるマクロファージの免疫応答、活性酸素生成系の食細胞NADPHオキシダーゼのタンパク質間相互作用、誘導型NO合成酵素(iNOS)の転写制御機構等を明らかにする。これらの知見に基づき、E.tarda強毒株flagellinによる宿主免疫回避の分子機構を解明する。

Outline of Final Research Achievements

In this study, we examined the effects of recombinant flagellins from high and low virulent strains of Edwardsiella tarda (E. tarda) on macrophage cell line in terms of the induction of NO, intracellular ROS, and TNF-α and so on. As the results, both recombinant flagellins induced NO production, mRNA expression level of iNOS, and intracellular ROS production in macrophages. Also, the secretion of TNF-α and its mRNA expression level were increased by treatment of both flagellins. These results indicate that the recombinant flagellins from different virulent E. tarda strains can stimulate macrophages with nearly equal levels as judged by the parameters tested, even though they are differences in the structure and molecular weight.

Academic Significance and Societal Importance of the Research Achievements

魚類の代表的細菌感染症であるエドワジエラ症の原因菌Edwardsiella tarda (E. tarda) は、ヒラメ、マダイ、ウナギ等の多くの養殖魚種に対して高い病原性を示し、実用的な予防・治療法の開発が難航している。特に、E. tardaがマクロファージ等の貪食細胞内に取り込まれても殺菌されずに増殖し続ける現象 (宿主免疫回避) が、その要因と考えられている。本研究で得られた成果は、E. tardaによる宿主免疫回避機構の解明に繋がるものであり、宿主 (ヒラメ) の生体反応を巧みに制御し、生体側病原因子を抑制するという新しい治療法に多くの情報を提供できる。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (5 results)

All 2023 2022 2020

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (3 results) Book (1 results)

  • [Journal Article] Cloning, DNA sequence, and expression of flagellins from high and low virulence strains of Edwardsiella tarda and their macrophage-stimulating activities2023

    • Author(s)
      Xiao-Mi Sun, Asami Yoshida, Fukutarou Toutani, Takahiro Shimizu, Tatsuya Oda, Kiyoshi Osatomi
    • Journal Title

      Microbial Pathogenesis

      Volume: 176 Pages: 105993-105993

    • DOI

      10.1016/j.micpath.2023.105993

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Presentation] 魚類エドワジエラ症原因菌Edwardsiella tarda が有する宿主免疫回避機構の解明2022

    • Author(s)
      田丸悠文・Xiao-Mi Sun・吉田朝美・長富 潔
    • Organizer
      第44回蛋白質と酵素の構造と機能に関する九州シンポジウム
    • Related Report
      2022 Annual Research Report
  • [Presentation] 酸化ストレスに伴うヒラメCu,Zn-SOD遺伝子のプロモーター解析2022

    • Author(s)
      Xiao-Mi Sun・吉田朝美・Yi-Li Gao・Yan-Rong Jiang・田丸悠文・長富 潔
    • Organizer
      令和3年度日本水産学会九州支部大会
    • Related Report
      2021 Research-status Report
  • [Presentation] E.tarda由来組換えflagellin刺激によるヒラメCu,Zn-SOD遺伝子の転写制御機構の解析2020

    • Author(s)
      清水貴広・Gao Yili・吉田朝美・長富 潔
    • Organizer
      令和2年度日本水産学会九州支部大会
    • Related Report
      2020 Research-status Report
  • [Book] Effect of Bacterial Infection on the Expression of Stress Proteins and Antioxidative Enzymes in Japanese flounder. H.-J. Ceccaldi et al. (eds.), Evolution of Marine Coastal Ecosystems under the Pressure of Global Changes2020

    • Author(s)
      Toshiki Nakano, Kiyoshi Osatomi, Nanami Miura, Yoko Aikawa-Fukuda, Kinya Kanai, Asami Yoshida, Hitoshi Shirakawa, Akiko Yamauchi, Toshiyasu Yamaguchi, and Yoshihiro Ochiai
    • Total Pages
      17
    • Publisher
      Springer-Nature AG
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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