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Molecular and cellular signaling analysis of hypoxic adaptation of pathogenic yeast Cryptococcus neoformans

Research Project

Project/Area Number 16K08769
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Bacteriology (including mycology)
Research InstitutionChiba University

Principal Investigator

KAWAMOTO Susumu  千葉大学, 真菌医学研究センター, 客員教授 (80125921)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords低酸素 / 細胞周期 / 病原酵母 / 環境応答 / シグナル伝達 / 病原真菌 / 低酸素ストレス / 細胞周期制御 / クリプトコックス / 真菌 / 感染症 / 低酸素応答
Outline of Final Research Achievements

For the pathogenic yeast Cryptococcus neoformans to cause disease, it must adapt to the host environment, which is very different from the natural habitat. We have reported the role of the transcription factor gene in slowdown of proliferation and survival under reduced aeration in C. neoformans. We identified and analyzed, in C. neoformans, components of the G2-M control machinery, Wee1 kinase and Cdc25 phosphatase homologues, which are involved in the inhibition and activation, respectively, of the Cdk1-cyclin complex at the mitotic entry checkpoint. Our study demonstrated a tight molecular link between hypoxic adaptation and cell cycle regulation in C. neoformans. We discussed the molecular link between them, and also infection model using silkworm, and neuro-tropism of C. neoformans.

Academic Significance and Societal Importance of the Research Achievements

病原酵母Cryptococcus neoformans (クリプトコックス) は我が国に常在する真菌の中で最も病原性が強く、易感染患者、特にエイズ患者の直接死因としても極めて重要な真菌であり、さらなるその基礎研究が強く望まれて来た。我々は、クリプトコックスの細胞周期制御機構を研究中に、本菌のユニークな低酸素ストレスへの応答現象を見出し、解析して来たが、本研究により、本菌の低酸素ストレス応答機構や細胞周期制御機構、また、それらの関連性の解析、考察を進め、分子細胞学的理解がさらに進んだ。

Report

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

Research Products

(27 results)

All 2018 2017 2016 Other

All Int'l Joint Research (9 results) Journal Article (7 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 4 results,  Acknowledgement Compliant: 2 results) Presentation (11 results) (of which Int'l Joint Research: 6 results,  Invited: 4 results)

  • [Int'l Joint Research] パラツキー大学(チェコ)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] デブレツェン大学(ハンガリー)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] 貴州医科大学(中国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] デブレツェン大学(ハンガリー)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] パラツキー大学(チェコ)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] 貴州医科大学(中国)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] デブレツェン大学(ハンガリー)

    • Related Report
      2016 Research-status Report
  • [Int'l Joint Research] パラツキー大学(チェコ)

    • Related Report
      2016 Research-status Report
  • [Int'l Joint Research] 貴州医科大学(中国)

    • Related Report
      2016 Research-status Report
  • [Journal Article] 病原真菌クリプトコックスの中枢神経親和性の機序の理解に向けて2018

    • Author(s)
      川本 進
    • Journal Title

      Neuroinfection

      Volume: 23 Pages: 84-89

    • Related Report
      2018 Annual Research Report
  • [Journal Article] 病原酵母クリプトコックスの低酸素ストレス応答2018

    • Author(s)
      川本 進
    • Journal Title

      細胞

      Volume: 50 Pages: 44-47

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] A novel Zn2-Cys6 transcription factor AtrR plays a key role in an azole resistance mechanism of Aspergillus fumigatus by co-regulating cyp51A and cdr1B expressions.2017

    • Author(s)
      Hagiwara D, Miura D, Shimizu K, Paul S, Ohba A, Gonoi T, Watanabe A, Kamei K, Shintani T, Moye-Rowley WS, Kawamoto S, Gomi K.
    • Journal Title

      PLOS Pathogens

      Volume: -

    • DOI

      10.1371/journal.ppat.1006096

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Temperature during conidiation affects stress tolerance, pigmentation, and trypacidin accumulation in the conidia of the airborne pathogen Aspergillus fumigatus2017

    • Author(s)
      Hagiwara Daisuke、Sakai Kanae、Suzuki Satoshi、Umemura Myco、Nogawa Toshihiko、Kato Naoki、Osada Hiroyuki、Watanabe Akira、Kawamoto Susumu、Gonoi Tohru、Kamei Katsuhiko
    • Journal Title

      PLoS One

      Volume: 12

    • DOI

      10.1371/journal.pone.0177050

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Putative orotate transportes of Cryptococcus neoformans, Oat1, is a member of the NCS1/PRT transporter super family and its loss causes attenuation of virulens.2017

    • Author(s)
      Akira Toh-e, Misako Ohkusu, Kiminori Shimizu, Azusa Takahashi-Nakaguchi, Susumu Kawamoto, Naruhiko Ishiwada, Akira Watanabe, Katsuhiko Kamei
    • Journal Title

      Current Genetics

      Volume: 印刷中 Pages: 697-707

    • DOI

      10.1007/s00294-016-0672-5

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Silkworm infection model to evaluate antifungal drugs for Cryptococcosis2017

    • Author(s)
      Matsumoto Yasuhiko, Ishii Masaki, Shimizu Kiminori, Kawamoto Susumu, Sekimizu Kazuhisa
    • Journal Title

      Medical Mycology Journal

      Volume: 58

    • NAID

      130006233755

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Comparative transcriptome analysis revealing dormant conidia and germination associated genes in Aspergillus species: an essential role for AtfA in conidial dormancy2016

    • Author(s)
      Hagiwara D, Takahashi H, Kusuya Y, Kawamoto S, Kamei K, Gonoi T
    • Journal Title

      BMC Genomics

      Volume: 17 Pages: 358-358

    • DOI

      10.1186/s12864-016-2689-z

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Cell cycle regulation and hypoxic adaptation in the pathogenic yeast Cryptococcus neoformans2018

    • Author(s)
      Kawamoto Susumu, Moranova Zuzana, Virtudazo Eric, Ohkusu Misako, Raclavsky Vladislav
    • Organizer
      2018 Annual Meeting of American Society for Biochemstry and Molecular Biology (Experimental Biology 2018)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Towards understanding the molecular link between cell cycle regulation and hypoxic adaptation in Cryptococcus neoformans2018

    • Author(s)
      Kawamoto Susumu, Moranova Zuzana, Virtudazo Eric, Ohkusu Misako, Suganami Akiko, Tamura Yutaka, Raclavsky Vladislav
    • Organizer
      20th Congress of International Society for Human and Animal Mycology (ISHAM)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Towards understanding cell cycle regulation, hypoxic adaptation, and neuro-tropism in the pathogenic yeast Cryptococcus neoformans2018

    • Author(s)
      Kawamoto Susumu, Moranova Zuzana, Virtudazo Eric, Ohkusu Misako, Raclavsky Vladislav
    • Organizer
      The 7th Global Network Forum on Infection and Immunity
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Cell cycle regulation in the pathogenic yeast Cryptococcus neoformans and the model yeast Saccharomyces cerevisiae2017

    • Author(s)
      Kawamoto Susumu, Virtudazo Eric, Ohkusu Misako, Suganami Akiko, Tamura Yutaka
    • Organizer
      International Union of Microbiological Societies 2017 Singapore Congress
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Temperature during conidation affects stress tolerance, pigmentation, and trypacidin accumulation in the conidia of the the airborne pathogen Aspergillus fumigatus2017

    • Author(s)
      Hagiwara Daisuke, Sakai Kanae, Nogawa Toshihiko, Kato Naoki, Osada Hiroyuki, Watanabe Akira, Kawamoto Susumu, Gonoi Tohru, Kamei Katsuhiko
    • Organizer
      International Union of Microbiological Societies 2017 Singapore Congress
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] クリプトコックス感染症に対する抗真菌薬のカイコを用いた評価2017

    • Author(s)
      松本靖彦、石井雅樹、清水公徳、川本進、関水和久
    • Organizer
      真菌症フォーラム 第23回学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 糸状菌の薬剤応答機構を統御する転写因子の発見2017

    • Author(s)
      萩原大祐、川本 進
    • Organizer
      第192回 酵母細胞研究会例会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 病原真菌クリプトコックスの中枢神経親和性の機序の理解に向けて2017

    • Author(s)
      川本 進
    • Organizer
      第22回日本神経感染症学会総会・学術大会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Our recent research projects of Cryptococcus yeasts: multilocus sequence typing (MLST)analysis of Cryptococcus gattii isolated in Brazil.2016

    • Author(s)
      Susumu Kawamoto
    • Organizer
      Guiyang Medical University seminar
    • Place of Presentation
      Guiyang, China
    • Year and Date
      2016-12-09
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Functional analyses of novel proteins of mycoviruses infecting phytopathogenic fungi using heterologous expression system in Saccharomyces cerevisiae.2016

    • Author(s)
      Hiromitsu Moriyama, Syun-Ichi Urayama, Yuri Kimura, Toshiyuki Fukuhara, Akio Toh-e, Susumu Kawamoto
    • Organizer
      14th International Congress on Yeasts
    • Place of Presentation
      Awaji Yumebutai International Conference Center, Hyogo, Japan
    • Year and Date
      2016-09-11
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Towards understanding cell cycle regulation in the pathogenic Cryptococcus neoformans and Saccharomyces cerevisiae.2016

    • Author(s)
      Susumu Kawamoto, Eric Virtudazo, Misako Ohkusu, Akiko Suganami, Yutaka Tamura
    • Organizer
      2016 Annual Meeting of American Society of Biochemistry and Molecular Biology (EB 2016),
    • Place of Presentation
      San Diego, California, USA
    • Year and Date
      2016-04-02
    • Related Report
      2016 Research-status Report

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

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