カンジダ感染の発症メカニズムを解明し感染経路遮断へ(Blocking off highway to infections)

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2026-03-20 フランス国立科学研究センター(CNRS)

フランス国立科学研究センター(CNRS)の研究チームは、病原体が体内で拡散する際に利用する「感染の高速道路」とも呼ばれる細胞間の移動経路を遮断する新たな仕組みを解明した。研究では、ウイルスや細菌が細胞骨格や細胞間接触構造を利用して効率的に広がる過程に着目し、その移動に必要な分子機構を特定した。特定のタンパク質の働きを阻害することで、病原体の細胞間伝播が大幅に抑制されることが示された。この成果は、従来の抗ウイルス・抗菌薬とは異なる「拡散阻止型」の新しい治療戦略の可能性を示すものであり、薬剤耐性問題への対応にも貢献が期待される。

カンジダ感染の発症メカニズムを解明し感染経路遮断へ(Blocking off highway to infections)
Right: ovoid and filamentous “Candida albicans”. To the right: a macrophage (an immune defence cell) being destroyed by three “Candida”.Dennis Kunkel / Science Photo Library ; Kevin Mackenzie, University of Aberdeen / Wellcome Collection CC BY 4.0

<関連情報>

リボソーム生合成の阻害による細胞質内混雑の減少は、カンジダ・アルビカンスの糸状成長を誘発する可能性がある Decreased cytoplasmic crowding via inhibition of ribosome biogenesis can trigger Candida albicans filamentous growth

Antonio Serrano,Charles Puerner,Louis Chevalier,Emily Plumb,Johannes Elferich,Stephen Diggs,Ludwig Roman Sinn,Nikolaus Grigorieff,Markus Ralser,Morgan Delarue,Martine Bassilana & Robert Alan Arkowitz
Nature Microbiology  Published:10 December 2025
DOI:https://doi.org/10.1038/s41564-025-02205-2

Abstract

The human fungal pathogen Candida albicans undergoes a morphological transition from a budding yeast to a filamentous form, which is associated with pathogenesis. Various cues mediate this transition including intracellular reorganization. The cytoplasm is densely packed with proteins including large macromolecular complexes, such as ribosomes, and hence, molecular crowding can impact a range of cellular processes. However, the relationship between cytoplasmic molecular crowding and morphological growth states is unclear. Using a fluorescent microrheological probe and single particle tracking, we observed a striking decrease in molecular crowding during filamentous growth in C. albicans. On the basis of simulations, proteomics and structural data from in situ cryogenic electron microscopy, we show that the reduction in crowding is due to a decrease in ribosome concentration that results in part from an inhibition of ribosome biogenesis, combined with an increase in cytoplasmic volume, leading to a dilution of ribosomes. Filamentation was enhanced in a mutant defective in ribosome biogenesis, while translation was not affected, suggesting that inhibition of ribosome biogenesis is a trigger for C. albicans morphogenesis. Overall, we show that filamentous growth is associated with reduced cytoplasmic crowding via changes in ribosome concentration, suggesting that combination therapies in which ribosome biogenesis is also targeted may be advantageous.

生物化学工学
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