Degradation of fibrinogen and collagen by staphopains, cysteine proteases released from Staphylococcus aureus
Degradation of fibrinogen and collagen by staphopains, cysteine proteases released from Staphylococcus aureus
复制标题
DOI：
10.1099/mic.0.044503-0
复制
发表时间：
2011-03-01
期刊：
影响因子：
2.8
通讯作者：
Imamura, Takahisa
中科院分区：
文献类型：
--
作者：
Ohbayashi, Takehisa;Irie, Atsushi;Imamura, Takahisa
金黄色葡萄球菌是革兰氏阳性脓毒症中最常见的分离病原体，通常并发凝血障碍，并且是由细菌破坏心内膜组织引起的感染性心内膜炎的主要原因。该细菌分泌称为葡萄球菌蛋白酶A（ScpA）和葡萄球菌蛋白酶B（Ssp B）的半胱氨酸蛋白酶。为了研究与凝血障碍和组织破坏有关的葡萄球菌蛋白酶的毒力活性，我们研究了它们对胶原蛋白（主要组织成分之一）和血浆凝血的影响。两种葡萄球菌蛋白酶均以剂量和活性依赖性方式延长血浆部分凝血活酶时间，SspB的效力是ScpA的三倍。葡萄球菌蛋白酶还延长了血浆和纤维蛋白原的凝血酶时间，表明这些酶可通过纤维蛋白原降解导致血浆凝血受损。SspB在C-末端区域非常有效地切割纤维蛋白原A α链，而ScpA降解它相当缓慢。这解释了前一种酶削弱纤维蛋白原凝血的上级能力。酶活性葡萄球菌蛋白酶，在浓度低至10纳米，降解胶原蛋白具有可比的效率。这些结果表明，葡萄球菌蛋白酶降解纤维蛋白原和胶原蛋白的新的毒力活动，并建议葡萄球菌蛋白酶在葡萄球菌感染引起的凝血损伤和组织破坏的参与。
Staphylococcus aureus is the most frequently isolated pathogen in Gram-positive sepsis often complicated by a blood clotting disorder, and is the leading cause of infective endocarditis induced by bacterial destruction of endocardial tissues. The bacterium secretes cysteine proteases referred to as staphopain A (ScpA) and staphopain B (SspB). To investigate virulence activities of staphopains pertinent to clotting disorders and tissue destruction, we examined their effects on collagen, one of the major tissue components, and on plasma clotting. Both staphopains prolonged the partial thromboplastin time of plasma in a dose- and activity-dependent manner, with SspB being threefold more potent than ScpA. Staphopains also prolonged the thrombin time of both plasma and fibrinogen, indicating that these enzymes can cause impaired plasma clotting through fibrinogen degradation. Whereas SspB cleaved the fibrinogen A alpha-chain at the C-terminal region very efficiently, ScpA degraded it rather slowly. This explains the superior ability of the former enzyme to impair fibrinogen clottability. Enzymically active staphopains, at concentrations as low as 10 nM, degraded collagen with comparable efficiency. These results show novel virulence activities of staphopains in degrading fibrinogen and collagen, and suggest an involvement of staphopains in the clotting impairment and tissue destruction caused by staphylococcal infection.