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

Abstract

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 cellsurface-associated plasmin cannot be regulated by the serum inhibitor ac2-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.

Quantitative analysis of Borrelia burgdorferi gene expression in naturally (tick) infected mouse strains

“…), in spite of extensive expansion of the spirochete population, indicates that host factors other than those associated with specific immunity interfere with gene expression in spirochetes. Although elusive so far, it is possible that host molecules such as fibronectin [26], proteoglycan [29,35], glycosphingolipids [4], decorin [17], complement regulators [31], plasminogen [12,21] and integrins [11], which serve as receptors for spirochetal outer surface proteins, participate in this process(es).…”

“…Coevolution of this tick-borne spirochete and mice, its main natural reservoir host [3], have led to a steady state between pathogen and mammals that is characterized, in most cases, by persistence of B. burgdorferi and lack of disease symptoms in the carrier [57]. There is increasing evidence that the pathogen has evolved various strategies to evade innate and adaptive immunity, including binding of host-derived factors, such as plasminogen [21] and complement inhibitors [31], differential up-and down-regulation of outer surface proteins (Osp) [2,15,38,57] and antigenic variation [65]. In fact, recent data suggest that specific antibodies to OspC may select for surface-antigen non-expressors thereby contributing to spirochetal persistence in mice [36].…”

Purification of native α-enolase from Streptococcus pneumoniae that binds plasminogen and is immunogenic

“…Important gram-negative pathogens including Neisseria meningitidis, Haemophilus influenzae, Borrelia burgdorferi, Salmonella enterica and Helicobacter pylori also bind substantial amounts of plasminogen [11][12][13][14]. Surface-bound plasmin enhances penetration of B. burgdorferi through artificial endothelial monolayers [15].…”

Biology of Infection with Borrelia burgdorferi

“…Carefully controlling for variables other than OspC has not been possible in such studies, since additional genome components of these isolates also differ. Recently, the invasive OspC protein types were shown to bind plasminogen [131], a trait shared with other B. burgdorferi proteins [133,134] that was suggested to facilitate B. burgdorferi infection of mammals and ticks [135].…”