Metabolic modulation: Pneumocystis phosphoglucomutase is a target influencing host recognition

Q1 Immunology and Microbiology Cell Surface Pub Date : 2024-03-25 DOI:10.1016/j.tcsw.2024.100123

Theodore J. Kottom , Eva M. Carmona , Bernd Lepenies , Andrew H. Limper

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Abstract

Herein, this manuscript explores the significance of the phosphoglucomutase (PGM) enzyme in Pneumocystis spp., focusing on its role in fungal surface mannoprotein formation. Through expression of the Pneumocystis murina Pmpgm2 in a Saccharomyces cerevisiae pgm2Δ strain, we demonstrate restoration of binding to the mannose receptor (MR) and macrophages to wildtype yeast levels in this complemented strain. Gas Chromatography-Mass Spectroscopy (GC-MS) confirmed reduced mannose content in the pgm2Δ yeast strain compared to the wild-type and complemented Pmpgm2 cDNA-expressing strains. This study underscores fungal PGM function in dolichol glucosyl phosphate biosynthesis, crucial for proper cell wall mannoprotein formation. Furthermore, highlighting the conservation of targetable cysteine residues across fungal pathogens, PGM inhibition maybe a potential therapeutic strategy against a broad spectrum of fungal infections.

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代谢调节：肺孢子虫磷酸葡聚糖酶是影响宿主识别的靶标

在此，本手稿探讨了肺炎囊菌属中磷酸葡萄糖转氨酶（PGM）的意义，重点是其在真菌表面甘露糖蛋白形成中的作用。通过在酿酒酵母 pgm2Δ 菌株中表达鼠肺孢子虫 Pmpgm2，我们证明在这种互补菌株中，与甘露糖受体（MR）和巨噬细胞的结合恢复到了野生型酵母的水平。气相色谱-质谱（GC-MS）证实，与野生型和 Pmpgm2 cDNA 表达互补株相比，pgm2Δ 酵母菌株中的甘露糖含量降低了。这项研究强调了真菌 PGM 在磷酸 Dolichol 葡萄糖基生物合成中的功能，这对细胞壁甘露糖蛋白的正常形成至关重要。此外，由于真菌病原体的半胱氨酸残基具有可靶向性，因此抑制 PGM 可能是一种针对多种真菌感染的潜在治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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