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Elucidation of molecular mechanism of persistent infection of Leptospira interrogans in maintenance host animal

Research Project

Project/Area Number 16K08797
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Bacteriology (including mycology)
Research InstitutionNational Institute of Infectious Diseases

Principal Investigator

Koizumi Nobuo  国立感染症研究所, 細菌第一部, 主任研究官 (10333361)

Research Collaborator Sasaki Yuya  
Sugiyama Himomu  
Tomizawa Rina  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywordsレプトスピラ / 維持宿主 / 持続感染
Outline of Final Research Achievements

To identify genes of Leptospira interrogans, a zoonotic bacterium, essential for persistent infection in kidney tissues of maintenance hast animals, we conducted infection experiments of rats using Leptospira mutants created by random transposon mutagenesis. A group of 96 mutants or a group of 414 mutants was inoculated to rats.
Then, leptospiral DNA sequences adjacent to transposon from inoculum and kidney culture were sequenced by next generation sequencer and the sequences were mapped to the reference genome. As a result, two and nine genes were not detected in the kidney culture of 96 mutant- and 414 mutant-inoculated rats, respectively, suggesting that these genes are essential for persistent infection in rats.

Academic Significance and Societal Importance of the Research Achievements

本研究によって病原性レプトスピラにおいて効率的なトランスポゾン挿入変異法を確立し,動物感染実験と次世代シーケンサーを用いた大規模シーケンシングによって,感染に必須なレプトスピラ遺伝子の網羅的同定が可能となった.本研究によって明らかとなった,また今後この方法により同定されるレプトスピラ因子をターゲットとして,レプトスピラの腎臓定着を阻害できるような薬剤やワクチンの開発につながることが期待され,レプトスピラ症の制御およびヒトの健康増進に寄与しうると考えられる.

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report

Research Products

(4 results)

All 2018 2017

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (2 results)

  • [Journal Article] Leptospiral flagellar sheath protein FcpA interacts with FlaA2 and FlaB1 in Leptospira biflexa2018

    • Author(s)
      Sasaki Yuya、Kawamoto Akihiro、Tahara Hajime、Kasuga Kie、Sato Ryoichi、Ohnishi Makoto、Nakamura Shuichi、Koizumi Nobuo
    • Journal Title

      PLOS ONE

      Volume: 13

    • DOI

      10.1371/journal.pone.0194923

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Male-specific pulmonary hemorrhage and cytokine gene expression in golden hamster in early-phase Leptospira interrogans serovar Hebdomadis infection2017

    • Author(s)
      Tomizawa Rina、Sugiyama Hiromu、Sato Ryoichi、Ohnishi Makoto、Koizumi Nobuo
    • Journal Title

      Microbial Pathogenesis

      Volume: 111 Pages: 33-40

    • DOI

      10.1016/j.micpath.2017.08.016

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] レプトスピラ感染ハムスターの組織病理とサイトカイン遺伝子発現の雌雄間比較2017

    • Author(s)
      冨澤莉那,杉山広,佐藤令一,大西真,小泉信夫
    • Organizer
      第54回レプトスピラシンポジウム
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-22
    • Related Report
      2016 Research-status Report
  • [Presentation] Gender difference of histopathology and cytokine gene expression in hamsters in Leptospira infection2017

    • Author(s)
      冨澤莉那,小泉信夫,杉山広,佐藤令一,大西真
    • Organizer
      第90回日本細菌学会総会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-19
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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