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.
Fuchs
H
H
Institute for Immunology, University of Heidelberg, Germany.
Wallich
R
R
Simon
M M
MM
Kramer
M D
MD
D000954:Antigens, Surface / Q000378:metabolism*; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D001428:Bacterial Vaccines; D015748:Borrelia burgdorferi Group / Q000378:metabolism*; D004789:Enzyme Activation; D005341:Fibrinolysin / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008074:Lipoproteins; D008239:Lysine / Q000737:chemistry; D010958:Plasminogen / Q000378:metabolism*; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D011994:Recombinant Proteins
D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D005353:Fibronectins; D008074:Lipoproteins; C072045:OspA protein; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D011994:Recombinant Proteins; D010958:Plasminogen; D005341:Fibrinolysin; D008239:Lysine