当糖越多越好时,GPI 侧链修饰会在原生动物感染过程中产生毒性较低的表型。

IF 5.1 1区 生物学 Q1 MICROBIOLOGY mBio Pub Date : 2024-11-13 DOI:10.1128/mbio.02740-24
Frank Seeber
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引用次数: 0

摘要

糖基磷脂酰肌醇(GPI)单位(锚或游离形式)侧链修饰的组装和功能尚不明确。在最近的一项研究中,确定了原生动物寄生虫弓形虫的两种酶 PIGJ 和 PIGE,并证明它们参与了此类 GPI 侧链的组装(J. A. Alvarez, E. Gas-Pascual, S. Malhi, J. C. Sánchez-Arcila, et al., mBio 15:e00527-24, 2024, https://doi.org/10.1128/mbio.00527-24)。PIGJ 向 GPI 核心结构添加 N-乙酰半乳糖胺,而 PIGE 随后添加末端葡萄糖。与 PIGE 基因敲除相反,PIGJ 基因缺失会导致侧链缺失,并显著增加受感染小鼠的死亡率。侧链的缺失导致清道夫受体 CD36 与突变寄生虫的结合增加。在 galectin-3 基因敲除小鼠中,侧链缺陷寄生虫的毒性表型基本消失。虽然确切的机制还有待更多的实验来阐明,但这些发现首次证明了 GPI 侧链在寄生虫-宿主体内相互作用中的重要性。
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When more sugar is better-a GPI side chain modification results in a less virulent phenotype during a protozoan infection.

The assembly and function of side chain modifications of glycosylphosphatidylinositol (GPI) units (anchors or free forms) are poorly defined. In a recent study, two enzymes, PIGJ and PIGE, of the protozoan parasite Toxoplasma gondii were identified and shown to be involved in the assembly of such GPI side chains (J. A. Alvarez, E. Gas-Pascual, S. Malhi, J. C. Sánchez-Arcila, et al., mBio 15:e00527-24, 2024, https://doi.org/10.1128/mbio.00527-24). PIGJ adds N-acetylgalactosamine to the GPI core structure, while PIGE subsequently adds a terminal glucose. Deletion of PIGJ resulted in the loss of the side chain and, strikingly, increased mortality in infected mice, in contrast to PIGE knockouts. Absence of the side chain led to increased binding of the scavenger receptor CD36 to mutant parasites. In galectin-3 knockout mice, the virulent phenotype of side-chain-deficient parasites was largely lost. While the exact mechanisms remain to be elucidated by more experiments, these findings provide the first evidence for the importance of GPI side chains in parasite-host interactions in vivo.

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来源期刊
mBio
mBio MICROBIOLOGY-
CiteScore
10.50
自引率
3.10%
发文量
762
审稿时长
1 months
期刊介绍: mBio® is ASM''s first broad-scope, online-only, open access journal. mBio offers streamlined review and publication of the best research in microbiology and allied fields.
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