Department of Oral and Maxillo-Facial Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Microbiology (Reading). 2011 Mar;157(Pt 3):786-792. doi: 10.1099/mic.0.044503-0. Epub 2010 Nov 16.
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 Aα-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.
金黄色葡萄球菌是革兰氏阳性菌败血症中最常分离到的病原体，常伴有凝血功能障碍，也是细菌破坏心内膜组织引起感染性心内膜炎的主要原因。该细菌分泌半胱氨酸蛋白酶，称为葡萄球菌蛋白酶 A（ScpA）和葡萄球菌蛋白酶 B（SspB）。为了研究与凝血障碍和组织破坏相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）和血浆凝固的影响。两种葡萄球菌蛋白酶都以剂量和活性依赖性方式延长了血浆部分凝血活酶时间，其中 SspB 的活性比 ScpA 强三倍。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，表明这些酶可以通过纤维蛋白原降解导致血浆凝固受损。虽然 SspB 非常有效地在 C 末端区域切割纤维蛋白原 Aα链，但 ScpA 降解它的速度相当慢。这解释了前一种酶更能降低纤维蛋白原可凝性的原因。具有酶活性的葡萄球菌蛋白酶，浓度低至 10 nM 时，就能以相当的效率降解胶原蛋白。这些结果表明葡萄球菌蛋白酶在降解纤维蛋白原和胶原蛋白方面具有新的毒力活性，并提示葡萄球菌蛋白酶参与了由葡萄球菌感染引起的凝血障碍和组织破坏。
