病原性真菌の細胞壁形成に役立つ酵素を新たに発見(Newly ID’d enzyme helps pathogenic fungus build protective cell wall)

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2024-07-09 ワシントン大学セントルイス校

病原性真菌の細胞壁形成に役立つ酵素を新たに発見(Newly ID’d enzyme helps pathogenic fungus build protective cell wall)
(Photo: Leanor Haley/CDC)

医学部の研究者は、エイズ患者に肺感染症や致命的な髄膜炎を引き起こす真菌であるCryptococcus neoformansの細胞壁構築に関与する新しい酵素を発見しました。毎年約15万人がクリプトコッカス感染症で死亡しています。この真菌の細胞壁は他の病原性真菌とは異なり、多くの抗真菌薬に対して抵抗性があります。新たに発見された「グルカン整理酵素(Goe1)」は、真菌の細胞壁構築の理解を深め、新たな治療法の開発を示唆します。研究はタマラ・ドーリング教授とポスドク研究者リザ・ロザによって行われ、「Proceedings of the National Academy of Sciences」に発表されました。

<関連情報>

真菌のタンパク質は、グリコーゲンと細胞壁グルカンの両方を組織化する A fungal protein organizes both glycogen and cell wall glucans

Liza Loza and Tamara L. Doering
Proceedings of the National Academy of Sciences  Published:May 14, 2024
DOI:https://doi.org/10.1073/pnas.2319707121

Significance

All cells store glucose as intracellular polymers that can be mobilized for energy as needed. Yeast additionally use large amounts of glucose to build their walls, a key structure that distinguishes them from other cell types and whose synthesis is a proven drug target in fungal pathogens. This investigation of two proteins in a pathogenic yeast demonstrated unexpected connections between internal glucose polymers and cell walls. Surprisingly, formation of the intracellular polymer glycogen is needed for synthesis of specific wall structures. Further, a newly characterized protein both organizes glycogen formation and influences cell wall glucan composition. These findings are important for fundamental biological understanding and potentially for improving human health.

Abstract

Glycogen is a glucose storage molecule composed of branched α-1,4-glucan chains, best known as an energy reserve that can be broken down to fuel central metabolism. Because fungal cells have a specialized need for glucose in building cell wall glucans, we investigated whether glycogen is used for this process. For these studies, we focused on the pathogenic yeast Cryptococcus neoformans, which causes ~150,000 deaths per year worldwide. We identified two proteins that influence formation of both glycogen and the cell wall: glycogenin (Glg1), which initiates glycogen synthesis, and a protein that we call Glucan organizing enzyme 1 (Goe1). We found that cells missing Glg1 lack α-1,4-glucan in their walls, indicating that this material is derived from glycogen. Without Goe1, glycogen rosettes are mislocalized and β-1,3-glucan in the cell wall is reduced. Altogether, our results provide mechanisms for a close association between glycogen and cell wall.

医療・健康
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