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Development of novel antifungal chemotherapy based on vacuole-disruptive activity.

Research Project

Project/Area Number 24590532
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Bacteriology (including Mycology)
Research InstitutionOsaka City University

Principal Investigator

OGITA Akira  大阪市立大学, 都市健康・スポーツ研究センター, 准教授 (00244624)

Co-Investigator(Renkei-kenkyūsha) FUJITA Ken-ichi  大阪市立大学大学院, 理学研究科, 准教授 (10285281)
TANAKA Toshio  大阪市立大学大学院, 理学研究科, 教授 (10137185)
SHIMIZU Takashi  山口大学, 農学部, 准教授 (40320155)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords液胞破壊作用 / 液胞膜障害作用
Outline of Final Research Achievements

To attempt realization of a novel antifungal chemotherapy based on selective fungal vacuole-disruptive activities using amphotericin B, exploring novel amplifier factors and elucidating their action mechanism were performed. These studies showed that N-methyl-N"-dodecylguanidine, a synthetic analogue of the alkyl side chain of niphimycin, would be a candidate as an enhancer of activities of vacuole targeting antifungal antibiotics, in addition to allicin, an allyl sulfur compound from garlic, and partly revealed its mode of action.
Our results obtained with analyses of the mode of action suggested that the presence of ergosterol as a component in membranes and progression of autophagy induced execution of vacuole-disruption. We additionally proposed a practical approach to realize an antifungal chemotherapy via selective vacuole-disruptive activities.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (8 results)

All 2015 2014 2013 2012

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (5 results) (of which Invited: 1 results) Book (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Visualization analysis of the vacuole-targeting fungicidal activity of amphotericin B against the parent strain and an ergosterol-less mutant of Saccharomyces cerevisiae.2013

    • Author(s)
      Kang CK, Yamada K, Usuki Y, Ogita A, Fujita K, Tanaka T.
    • Journal Title

      Microbiology

      Volume: 159 Issue: Pt_5 Pages: 939-947

    • DOI

      10.1099/mic.0.065714-0

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] ヤナギタデ由来成分の真菌液胞膜破壊作用2015

    • Author(s)
      近藤拓也、荻田亮、藤田憲一、田中俊雄
    • Organizer
      日本農芸化学会2015年度大会
    • Place of Presentation
      岡山大学 津島キャンパス(岡山県・岡山市)
    • Year and Date
      2015-03-26 – 2015-03-29
    • Related Report
      2014 Annual Research Report
  • [Presentation] アンホテリシンBの真菌液胞膜障害作用におけるオートファジーの関与2015

    • Author(s)
      吉岡美知留、松岡研、山田圭一、荻田亮、藤田憲一、田中俊雄
    • Organizer
      日本農芸化学会2015年度大会
    • Place of Presentation
      岡山大学 津島キャンパス(岡山県・岡山市)
    • Year and Date
      2015-03-26 – 2015-03-29
    • Related Report
      2014 Annual Research Report
  • [Presentation] N-methyl-N”-dodecylguanidine によって増幅する Amphotericin B の真菌液胞膜破壊作用2014

    • Author(s)
      姜昌慶、山田圭一、荻田亮、藤田憲一、田中俊雄
    • Organizer
      第66回日本生物工学会大会
    • Place of Presentation
      札幌コンベンションセンター(北海道・札幌市)
    • Year and Date
      2014-09-09 – 2014-09-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] 天然由来成分を介助因子とする抗菌活性の増幅効果2013

    • Author(s)
      荻田亮、田中俊雄、藤田憲一
    • Organizer
      大阪府立大学・大阪市立大学 新技術説明会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] amphotericin B の 真菌液胞膜破壊作用を促進するN-methyl-N"-dodecylguanidineの作用機序2013

    • Author(s)
      姜昌慶、山田圭一、荻田亮、臼杵克之助、藤田憲一、田中俊雄
    • Organizer
      日本農芸化学会
    • Place of Presentation
      仙台市
    • Related Report
      2012 Research-status Report
  • [Book] 「食品・化粧品・医薬品への保存料・防腐剤の最適な配合法」1章2(9). 防腐剤/抗菌剤の効果増強剤としての天然由来成分の活用法.2014

    • Author(s)
      荻田亮、田中俊雄、藤田憲一
    • Publisher
      技術情報協会
    • Related Report
      2014 Annual Research Report
  • [Patent(Industrial Property Rights)] 防腐剤又は抗菌剤の効果増強剤2012

    • Inventor(s)
      荻田亮、藤田憲一、田中俊雄
    • Industrial Property Rights Holder
      荻田亮、藤田憲一、田中俊雄
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2012-234161
    • Filing Date
      2012-10-23
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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