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Development of therapy for fungal infections based on understanding the system to cope with iron starvation in pathogenic fungi

Research Project

Project/Area Number 16K08791
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Bacteriology (including mycology)
Research InstitutionSuzuka University of Medical Science

Principal Investigator

Nakayama Hironobu  鈴鹿医療科学大学, 薬学部, 教授 (40369989)

Co-Investigator(Kenkyū-buntansha) 森田 明広  鈴鹿医療科学大学, 薬学部, 助教 (20382228)
Research Collaborator Taguchi Hiroaki  
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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords鉄欠乏ストレス / 真菌感染症 / カンジダ / 病原性発現 / 標的分子 / 鉄欠乏 / 感染症 / ストレス応答 / 抗真菌薬 / 遺伝学 / 菌類 / ストレス / 薬学
Outline of Final Research Achievements

Current therapies for treating systemic fungal infection have limited effectiveness and have created problems of adverse reactions and drug resistance. These issues therefore motivate us to develop novel antifungals. We focused on stress response for iron starvation to identify potential targets for novel antifungals because iron starvation occurs in blood, where pathogenic fungi often infect. As the results of several studies including transcriptomics and fungal-infection models. we revealed that SEF1(transcription factor controlling iron uptake) and ATG32 (mitochondrial outer membrane protein required to initiate mitophagy) would be promising targets for antifungals among the factors induced by iron starvation. Furthermore, we also suggested that vacuolar-ATPase would be promising targets for antifungals although VPH2 (assembly factor of vacuolar-ATPase) does NOT participate in stress response to iron starvation directly.

Academic Significance and Societal Importance of the Research Achievements

本研究で得られた成果は、宿主体内での生存において重要となる鉄欠乏環境に適応した真菌の鉄恒常性の維持機構の解明に貢献する知見となる。また、深在性真菌症は免疫不全患者に発症する感染症として、医療の高度化や人口の高齢化などと関連して増加の一途をたどり、新しい真菌感染症の治療薬の開発が急務となっている社会背景において、有効な真菌感染の診断や治療につながる標的を提案するものである。

Report

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

    (17 results)

All 2019 2018 2017 2016

All Journal Article (7 results) (of which Peer Reviewed: 4 results,  Open Access: 6 results,  Acknowledgement Compliant: 1 results) Presentation (10 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results)

  • [Journal Article] Vacuolar proton-translocating ATPase is required for antifungal resistance and virulence of Candida glabrata.2019

    • Author(s)
      Minematsu A, Miyazaki T, Shimamura S, Nishikawa H, Nakayama H, Takazono T, Saijo T, Yamamoto K, Imamura Y, Yanagihara K, Kohno S, Mukae H, Izumikawa K.
    • Journal Title

      PLoS OneJan 23;14(1):e0210883.

      Volume: 14 Issue: 1 Pages: e0210883-e0210883

    • DOI

      10.1371/journal.pone.0210883

    • NAID

      120006987849

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Unexpected effects of azole transporter inhibitors on antifungal susceptibility in Candida glabrata and other pathogenic Candida species2017

    • Author(s)
      Nagayoshi Yohsuke、Miyazaki Taiga、Shimamura Shintaro、Nakayama Hironobu、Minematsu Asuka、Yamauchi Shunsuke、Takazono Takahiro、Nakamura Shigeki、Yanagihara Katsunori、Kohno Shigeru、Mukae Hiroshi、Izumikawa Koichi
    • Journal Title

      PLOS ONE

      Volume: 12 Issue: 7 Pages: e0180990-e0180990

    • DOI

      10.1371/journal.pone.0180990

    • NAID

      120006987443

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Promising Therapies for Fungal Infection Based on the Study to Elucidate Mechanisms to Cope with Stress in <I>Candida</I> Species [Translated Article]2017

    • Author(s)
      Hirai K, Inukai T, Nakayama H.
    • Journal Title

      Medical Mycology Journal

      Volume: 58 Issue: 2 Pages: E79-E86

    • DOI

      10.3314/mmj.17.007

    • NAID

      130006906294

    • ISSN
      2185-6486, 2186-165X
    • Related Report
      2017 Research-status Report
  • [Journal Article] Promising Therapies for Fungal Infection Based on the Study to Elucidate Mechanisms to Cope with Stress in Candida Species.2017

    • Author(s)
      Hirai K, Inukai T, Nakayama H.
    • Journal Title

      Med Mycol J

      Volume: 58

    • NAID

      130005172328

    • Related Report
      2016 Research-status Report
    • Open Access
  • [Journal Article] Iron-depletion promotes mitophagy to maintain mitochondrial integrity in pathogenic yeast Candida glabrata.2016

    • Author(s)
      Nagi M, Tanabe K, Nakayama H, Ueno K, Yamagoe S, Umeyama T, Ohno H, Miyazaki Y.
    • Journal Title

      Autophagy

      Volume: 12 Issue: 8 Pages: 1259-1271

    • DOI

      10.1080/15548627.2016.1183080

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Roles of vacuolar H+-ATPase in the oxidative stress response of Candida glabrata.2016

    • Author(s)
      Nishikawa H, Miyazaki T, Nakayama H, Minematsu A, Yamauchi S, Yamashita K, Takazono T, Shimamura S, Nakamura S, Izumikawa K, Yanagihara K, Kohno S, Mukae H.
    • Journal Title

      FEMS Yeast Res.

      Volume: 16 Issue: 5 Pages: fow054-fow054

    • DOI

      10.1093/femsyr/fow054

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] カンジダのストレス応答からみえてきた真菌症治療戦略2016

    • Author(s)
      平井一行、犬飼達也、中山浩伸
    • Journal Title

      Med Mycol J

      Volume: 57

    • NAID

      130005172328

    • Related Report
      2016 Research-status Report
    • Open Access
  • [Presentation] Role of Elm1 in cell wall integrity and virulence of Candida glabrata2018

    • Author(s)
      Yuya Ito, Taiga Miyazaki, Hironobu Nakayama, Akihiro Morita et al.,
    • Organizer
      ISHAM 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Aspergillus fumigatus の血清存在下の生育に関 与する因子の探索と病原性への影響2018

    • Author(s)
      犬飼 達也、梅山 隆、宇田 晶彦、青山 俊弘、中山 浩伸 他
    • Organizer
      第62回日本医真菌学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Exogenous sterol uptake: A potential cause of azalea resistance2018

    • Author(s)
      田辺公一、名木稔、犬飼達也、中山宏伸、梅山隆、山越智、中村茂樹、宮崎義継
    • Organizer
      第91回日本細菌学会・総会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 病原性および鉄欠乏環境下における<I>Candida glabrata</I>のマイトファジーの役割2017

    • Author(s)
      名木稔、田辺公一、上野圭吾、中山宏伸、中村茂樹、梅山隆、山越智、宮崎義継
    • Organizer
      第61回日本医真菌学会総会・学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Candida glabrataにおけるカルシニューリン関連分子Elm1の機能解析2017

    • Author(s)
      伊藤 裕也、宮崎 泰可、中山 浩伸、田中 大、田代 将人、島村 真太郎 、西條 知見、高園 ) 山本 和子、今村 圭文、泉川 公一、栁原 克、河野 茂 、迎 寛
    • Organizer
      第61回日本医真菌学会総会・学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 病原真菌 Candida glabrata のミトコンドリア選択的オートファ ジーと病原性2017

    • Author(s)
      名木 稔, ,田辺 公一, 上野 圭吾, 中山 浩伸, 中村 茂樹, 梅山 隆, 山越 智, 宮﨑 義継
    • Organizer
      第 90 回日本細菌学会総会
    • Place of Presentation
      仙台
    • Related Report
      2016 Research-status Report
  • [Presentation] Aspergillus fumigatus の血清存在下における菌糸生育に関連する因子の同定2016

    • Author(s)
      犬飼 達也、梅山 隆、山越 智、青山 俊弘、 中山 浩伸、名木 稔、田辺 公一、 中村 茂樹、宮﨑 義継
    • Organizer
      第 60 回日本医真菌学会総会・学術集会
    • Place of Presentation
      東京
    • Year and Date
      2016-10-01
    • Related Report
      2016 Research-status Report
  • [Presentation] Candida glabrata のミトコンドリア選択的オートファジー(マイトファジー)が病原性に及ぼす 影響2016

    • Author(s)
      名木 稔、田辺 公一、中山 浩伸、上野 圭吾、犬飼 達也、中村 茂樹、梅山 隆、山越 智、 大野 秀明、宮﨑 義継
    • Organizer
      第 60 回日本医真菌学会総会・学術集会
    • Place of Presentation
      東京
    • Year and Date
      2016-10-01
    • Related Report
      2016 Research-status Report
  • [Presentation] Iron-depletion promotes mitophagy in pathogenic yeast Candida glabrata2016

    • Author(s)
      Minoru Nagi, Koichi Tanabe, Hironobu Nakayama, Keigo Ueno, Satoshi Yamagoe, Takashi Umeyama, Hideaki Ohno, Yoshitsugu Miyazaki
    • Organizer
      14th International Conference on Yeasts (ICY2016)
    • Place of Presentation
      兵庫(淡路島)
    • Year and Date
      2016-09-12
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Candida glabrata のミトコンドリア選択的オートファジーと病原性2016

    • Author(s)
      名木 稔、田辺 公一、中山 浩伸、上野 圭吾、犬飼 達也、中村 茂樹、梅山 隆、山越 智、 大野 秀明、宮﨑 義継
    • Organizer
      第 60 回日本医真菌学会総会・学術集会
    • Place of Presentation
      東京
    • Related Report
      2016 Research-status Report

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

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