Clostridium septicum alpha-toxin is active against the parasitic protozoan Toxoplasma gondii and targets members of the SAG family of glycosylphosphatidylinositol-anchored surface proteins.
Clostridium septicum alpha-toxin is active against the parasitic protozoan Toxoplasma gondii and targets members of the SAG family of glycosylphosphatidylinositol-anchored surface proteins.
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败血梭菌 α 毒素对寄生原生动物弓形虫具有活性，并针对糖基磷脂酰肌醇锚定表面蛋白 SAG 家族的成员。
DOI：
10.1128/iai.70.8.4353-4361.2002
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发表时间：
2002
影响因子：
3.1
通讯作者：
Ward,GaryE
中科院分区：
文献类型：
--
作者：
Wichroski,MichaelJ;Melton,JodyA;Donahue,CarolynG;Tweten,RodneyK;Ward,GaryE
与许多其他原生动物寄生虫一样，糖基磷脂酰肌醇(GPI)锚定蛋白支配着弓形虫的表面。通过它的机制。GondiiGPI锚定蛋白被合成，并通过寄生虫膜的不寻常的三层膜结构运输到质膜，但在很大程度上仍不清楚。作为开发研究这些过程的工具的第一步，我们在这里展示了败血梭菌α-毒素，一种针对哺乳动物细胞表面GPI锚定蛋白受体的成孔毒素，具有抗GPI活性。刚地速殖子(50%有效浓度，0.2 nm)。超微结构研究表明，毒素处理局部破坏了质膜和内膜复合体底层膜之间的紧密物理连接，导致质膜大量向外延伸，最终使寄生虫溶解。毒素治疗还会导致寄生虫内质网肿胀，这为α-毒素是一种空泡毒素提供了第一个直接证据。甲型毒素与几种寄生虫GPI锚定蛋白结合，包括表面抗原3(SAG3)和SAG1。有趣的是，在强毒株RH和无毒株P之间观察到了毒素结合谱上的差异。α-毒素可能成为GPI锚定生物合成和GPI锚定蛋白转运的分子遗传学分析的有力实验工具。弓形虫和其他敏感的原生动物。
As is the case with many other protozoan parasites, glycosylphosphatidylinositol (GPI)-anchored proteins dominate the surface ofToxoplasma gondiitachyzoites. The mechanisms by whichT. gondiiGPI-anchored proteins are synthesized and transported through the unusual triple-membrane structure of the parasite pellicle to the plasma membrane remain largely unknown. As a first step in developing tools to study these processes, we show here thatClostridium septicumalpha-toxin, a pore-forming toxin that targets GPI-anchored protein receptors on the surface of mammalian cells, is active againstT. gondiitachyzoites (50% effective concentration, 0.2 nM). Ultrastructural studies reveal that a tight physical connection between the plasma membrane and the underlying membranes of the inner membrane complex is locally disrupted by toxin treatment, resulting in a massive outward extension of the plasma membrane and ultimately lysis of the parasite. Toxin treatment also causes swelling of the parasite endoplasmic reticulum, providing the first direct evidence that alpha-toxin is a vacuolating toxin. Alpha-toxin binds to several parasite GPI-anchored proteins, including surface antigen 3 (SAG3) and SAG1. Interestingly, differences in the toxin-binding profiles between the virulent RH and avirulent P strain were observed. Alpha-toxin may prove to be a powerful experimental tool for molecular genetic analysis of GPI anchor biosynthesis and GPI-anchored protein trafficking inT. gondiiand other susceptible protozoa.