Waller Amie K, Birch Katie, Gibbins Jonathan M, Clarke Simon R
School of Biological Sciences, University of Reading, Whiteknights, Reading RG6 6EX, UK.
Institute for Cardiovascular and Metabolic Research, University of Reading, Whiteknights, Reading RG6 6EX, UK.
Pathogens. 2022 Oct 26;11(11):1237. doi: 10.3390/pathogens11111237.
Infection by 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 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.
由[病原体名称未给出]感染是感染性心内膜炎（IE）的主要原因。该病原体激活血小板会导致其聚集和血栓形成，这被认为是IE发生发展和发病机制中的重要步骤。在此，我们表明一种分泌型半胱氨酸蛋白酶——葡萄球菌蛋白酶A，可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[细菌名称未给出]突变体的培养上清液触发血小板聚集的能力降低。纯化的葡萄球菌蛋白酶A的血小板激动剂活性被特异性抑制剂葡萄球菌抑素A抑制，从而表明其蛋白酶活性与激动作用有关。在全血中，使用原本不足以诱导血小板聚集的葡萄球菌蛋白酶A浓度时，观察到与胶原蛋白的结合增加和血栓形成。使用针对蛋白酶激活受体1和4的拮抗剂，我们证明了它们在介导葡萄球菌蛋白酶A诱导的血小板激活中的作用。
