Plasmin-coated borrelia Burgdorferi degrades soluble and insoluble components of the mammalian extracellular matrix.
Borrelia burgdorferi, the spirochetal agent of Lyme disease, binds plasminogen in vitro. Exogenously provided urokinase-type plasminogen (PLG) activator (uPA) converts surface-bound PLG to enzymatically active plasmin. In this study, we investigated the capacity of a B. burgdorferi human isolate, once complexed with plasmin, to degrade purified extracellular matrix (ECM) components and an interstitial ECM. In a modified enzyme-linked immunosorbent assay using immobilized, soluble ECM components, plasmin-coated B. burgdorferi degraded fibronectin, laminin, and vitronectin but not collagen. Incubation of plasmin-coated organisms with biosynthetically radiolabeled native ECM resulted in breakdown of insoluble glycoprotein, other noncollagenous proteins, and collagen, as measured by release of solubilized radioactivity. Radioactive release did not occur with untreated spirochetes or spirochetes treated with uPA or PLG alone. Kinetic and inhibition studies suggested that the breakdown of collagen was indirect and due to prior disruption of supportive ECM proteins. B. burgdorferi is an invasive bacterial pathogen that may benefit by use of the host's plasminogen activation system. The results of this study have identified mechanisms in which the spirochete can use this borrowed proteolytic activity to enhance 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.
Roemer
E J
EJ
Benach
J L
JL
D015748:Borrelia burgdorferi Group / Q000378:metabolism*; D003545:Cysteine / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005341:Fibrinolysin / Q000494:pharmacology*; D006801:Humans; D008715:Methionine / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology
D016326:Extracellular Matrix Proteins; D015842:Serine Proteinase Inhibitors; D008715:Methionine; D005341:Fibrinolysin; D003545:Cysteine