Chemical biology for dimorphism in Candida spp

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K05319
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 37030:Chemical biology-related
• Research Institution: Institute of Physical and Chemical Research (2021, 2023); Waseda University (2022)
• Principal Investigator: FUTAMURA YUSHI 国立研究開発法人理化学研究所, 環境資源科学研究センター, 上級研究員 (70525857)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 二形性 / 抗真菌剤

Outline of Final Research Achievements

To discover novel antifungal agents, we have screened for small molecules that interfere with the dimorphism of C. albicans based on their morphological changes and found that microbial metabolite compound X induced a hyphal form in C. albicans. A detailed time-lapse microscopy analysis suggested that compound X did not induce the morphological changes of C. albicans from yeast to hyphal form, but rather inhibited the branching of hyphae and the budding of lateral yeast during hyphal to yeast transition. Since the effects of this compound were inhibited by the addition of metal ion and other metal chelators showed a similar phenotype, metal chelating activity of this compounds is necessary for its antifungal activity, suggesting that metal chelators could be a new type of antifungal drug.

Free Research Field

ケミカルバイオロジー

Academic Significance and Societal Importance of the Research Achievements

これまで培養シャーレ中でカンジダの二形性を観察することは難しかったが、菌の培養条件を検討して、菌糸型ー酵母型の変換を評価できるようになった。この独自の表現型スクリーニングに探索リソース（微生物培養エキスなどの天然物資源、カンジダの遺伝子変異株コレクションの遺伝子資源）を組み合わせることで、カンジダの二形性制御機構に影響を与える化合物や遺伝子を迅速に見出すことができた。得られた化合物や二形性関連遺伝子についてはカイコを使った感染モデルで薬効や病原性を評価し、新しい創薬研究の足掛かりにしたい。