Abstract：
Infection by Staphylococcus aureus is the leading cause of infective endocarditis (IE). Activation of platelets by this pathogen results in their aggregation and thrombus formation which are considered to be important steps in the development and pathogenesis of IE. Here, we show that a secreted cysteine protease, staphopain A, activates human platelets and induces their aggregation. The culture supernatant of a scpA mutant deficient in staphopain A production was reduced in its ability to trigger platelet aggregation. The platelet agonist activity of purified staphopain A was inhibited by staphostatin A, a specific inhibitor, thus implicating its protease activity in the agonism. In whole blood, using concentrations of staphopain A that were otherwise insufficient to induce platelet aggregation, increased binding to collagen and thrombus formation was observed. Using antagonists specific to protease-activated receptors 1 and 4, we demonstrate their role in mediating staphopain A induced platelet activation.
摘要：
金黄色葡萄球菌感染是感染性心内膜炎（IE）的主要原因。该病原体对血小板的活化导致其聚集和血栓形成,这被认为是IE的发展和发病机理中的重要步骤。这里,我们发现一种分泌的半胱氨酸蛋白酶，staphoainA,激活人血小板并诱导其聚集。缺乏葡萄球菌蛋白酶A产生的scpA突变体的培养上清液触发血小板聚集的能力降低。纯化的staphostatinA抑制血小板激动剂活性，一种特定的抑制剂，从而暗示其蛋白酶活性的激动。在全血中，使用浓度的staphoppainA，否则不足以诱导血小板聚集，观察到与胶原和血栓形成的结合增加。使用对蛋白酶激活的受体1和4具有特异性的拮抗剂，我们证明了它们在介导staphoppainA诱导的血小板激活中的作用。
