Binding of human plasminogen and urokinase-type plasminogen activator to the Lyme disease spirochete, Borrelia burgdorferi.
Many bacteria that spread in the skin produce enzymes that digest extracellular matrix components. Borrelia burgdorferi spreads from a skin inoculation site to form the characteristic erythema migrans skin lesion. It was determined that B. burgdorferi does not produce collagenase, elastase, hyaluronidase, or other enzymes that digest extracellular matrix components. However, B. burgdorferi bound human plasmin, plasminogen (Pgn), and urokinase-type plasminogen activator (uPA). When spirochetes were sequentially incubated with Pgn and uPA, bioactive plasmin was generated on the surface of B. burgdorferi. B. burgdorferi did not produce an endogenous Pgn activator. Fluorochrome-conjugated uPA and Pgn colocalized to the terminus of the spirochete. In a mouse model, uPA-treated B. burgdorferi were more infectious than control spirochetes. Binding of host uPA and Pgn to form a bioactive extracellular matrix protease on B. burgdorferi represents a mechanism that could facilitate dissemination and localization of spirochetes to sites of vascular injury.
Klempner
M S
MS
Department of Medicine, New England Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA.
Noring
R
R
Epstein
M P
MP
McCloud
B
B
Hu
R
R
Limentani
S A
SA
Rogers
R A
RA
D000818:Animals; D025065:Borrelia burgdorferi; D015748:Borrelia burgdorferi Group / Q000378:metabolism* / Q000472:pathogenicity; D010450:Endopeptidases / Q000378:metabolism; D005260:Female; D005341:Fibrinolysin / Q000096:biosynthesis / Q000378:metabolism; D005456:Fluorescent Dyes; D006801:Humans; D008193:Lyme Disease / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal / Q000379:methods; D010958:Plasminogen / Q000378:metabolism*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
D005456:Fluorescent Dyes; D010958:Plasminogen; D010450:Endopeptidases; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator