The generation of enzymatically active plasmin on the surface of spirochetes.
The spirochete Borrelia burgdorferi, the etiologic agent of Lyme disease, is transmitted to the host by a feeding Ixodid tick. The spirochete subsequently disseminates through the skin, enters the bloodstream, and becomes systemic. A potential mechanism for this invasiveness was identified with the discovery that B. burgdorferi can bind components of the plasminogen activation system (PAS). The methodology for analyzing the generation of enzymatically active plasmin on the surface of this organism is given, and applied to measure spirochete viability, strain differences, and breakdown of extracellular matrix (ECM) macromolecules. Plasmin acquisition by B. burgdorferi was measured photometrically by a specific chromogenic substrate. The growth of B. burgdorferi in culture was not affected by the presence of active plasmin on the spirochete surface. Plasmin-coated B. burgdorferi degraded the purified (ECM) components fibronectin, laminin, and vitronectin, but not collagen. The addition of B. burgdorferi with surface plasmin to a radiolabeled, native ECM resulted in degradation of noncollagenous protein, as measured by release of solubilized radioactivity. Breakdown of purified ECM components or native ECM did not occur after exposure to untreated spirochetes or spirochetes treated with uPA or PLG alone. These results provide in vitro evidence that enzymatically active plasmin on the surface of B. burgdorferi may be partially responsible for its invasiveness.
Coleman
J L
JL
State of New York Department of Health, State University of New York at Stony Brook, Stony Brook, New York 11794-8691, USA.
Benach
J L
JL
D000818:Animals; D015748:Borrelia burgdorferi Group / Q000166:cytology / Q000472:pathogenicity / Q000502:physiology*; D005109:Extracellular Matrix / Q000382:microbiology; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005341:Fibrinolysin / Q000502:physiology*; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D007797:Laminin / Q000378:metabolism; D008193:Lyme Disease / Q000097:blood*; D051379:Mice; D008809:Mice, Inbred C3H; D010958:Plasminogen / Q000378:metabolism; D019096:Vitronectin / Q000378:metabolism
D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D007797:Laminin; D019096:Vitronectin; D010958:Plasminogen; D005341:Fibrinolysin