The outer surface protein A of the spirochete Borrelia burgdorferi is a plasmin(ogen) receptor.

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. IMAGES:

疏螺旋体属的伯氏疏螺旋体（Borrelia burgdorferi）是莱姆疏螺旋体病（Lyme borreliosis，即莱姆病）的病原体，可通过蜱媒传播至哺乳动物宿主。在人体中，该细菌可引发累及皮肤、关节、心脏及神经系统的复杂疾病。然而，这种多系统疾病的致病机制仍未完全阐明。为从蜱虫叮咬部位播散并侵袭多个器官组织，疏螺旋体必须穿透正常组织屏障，例如血管基底膜及其他有序排列的细胞外基质。来自其他侵袭性细菌感染的大量证据表明，疏螺旋体可能借助内源性或宿主源性酶类——尤其是蛋白酶——完成这一过程。本研究证实，伯氏疏螺旋体主要通过其细胞外表面脂蛋白A（outer cell surface lipoprotein A）结合人纤溶酶原（plasmin(ogen)）。当存在宿主源性纤溶酶原激活剂时，纤溶酶原与螺旋体受体的结合可加速活性纤溶酶的生成。与细胞表面结合的纤溶酶不受血清抑制剂α2-抗纤溶酶（alpha 2-antiplasmin）的调控，并可降解纤连蛋白等高分子量糖蛋白。研究表明，获取宿主源性蛋白酶纤溶酶原（plasmin(ogen)）有助于增强伯氏疏螺旋体的致病能力。图片：