Fuchs H, Wallich R, Simon M M, Kramer M D
Institute for Immunology, University of Heidelberg, Germany.
Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12594-8. doi: 10.1073/pnas.91.26.12594.
The spirochete Borrelia burgdorferi is the causative agent of Lyme borreliosis (Lyme disease) and is transmitted to mammalian hosts by tick vectors. In humans, the bacteria induce a complex disease, which involves the skin, joints, heart, and nervous system. However, the pathogenic principles of this multisystem illness are far from being understood. To disseminate from the site of the tick bite and invade multiple organ sites, spirochetes have to penetrate normal tissue barriers, such as vascular basement membranes and other organized extracellular matrices. Substantial evidence from other invasive bacterial infections suggest that spirochetes may use endogenous or host-derived enzymes--in particular, proteinases--for this purpose. Here we show that B. burgdorferi binds human plasmin(ogen)--mainly via its outer cell surface lipoprotein A. Binding of plasminogen to spirochetal receptor leads to an accelerated formation of active plasmin in the presence of host-derived plasminogen activator. The cell-surface-associated plasmin cannot be regulated by the serum inhibitor alpha 2-antiplasmin and degrades high-molecular-weight glycoproteins, such as fibronectin. It is suggested that the acquisition of host-derived proteinase plasmin(ogen) contributes to the pathogenicity of B. burgdorferi.
疏螺旋体伯氏疏螺旋体是莱姆病的病原体，通过蜱虫媒介传播给哺乳动物宿主。在人类中，这种细菌会引发一种复杂的疾病，累及皮肤、关节、心脏和神经系统。然而，这种多系统疾病的致病机制仍远未被了解。为了从蜱虫叮咬部位扩散并侵入多个器官部位，螺旋体必须穿透正常的组织屏障，如血管基底膜和其他有组织的细胞外基质。来自其他侵袭性细菌感染的大量证据表明，螺旋体可能为此目的使用内源性或宿主来源的酶——特别是蛋白酶。在这里，我们表明伯氏疏螺旋体主要通过其外细胞表面脂蛋白A与人纤溶酶（原）结合。在宿主来源的纤溶酶原激活剂存在的情况下，纤溶酶原与螺旋体受体的结合会加速活性纤溶酶的形成。细胞表面相关的纤溶酶不受血清抑制剂α2-抗纤溶酶的调节，并降解高分子量糖蛋白，如纤连蛋白。有人认为，获得宿主来源的蛋白酶纤溶酶（原）有助于伯氏疏螺旋体的致病性。
