Binding of human urokinase type plasminogen activator and plasminogen to Borrelia species.

Borrelia burgdorferi binds human urokinase plasminogen activator (uPA), which cleaves plasminogen (Pgn) to plasmin. The ability of other Borrelia species to bind uPA, Pgn, or both was investigated. Borrelia coriacae, Borrelia garinii, Borrelia parkeri, Borrelia anserina, and Borrelia turicatae were compared with infectious and noninfectious B. burgdorferi isolates. All Borrelia species lacked endogenous proteases capable of digesting casein, but all species bound human uPA and Pgn, generating Pgn-dependent proteolytic activity. There were no significant differences in the amount of plasmin, Pgn, or uPA bound per spirochete of the different species. On unfixed borreliae, fluorochrome-conjugated uPA bound to all species. Early binding was at the terminus of B. burgdorferi, whereas diffuse binding was observed on B. coriacae, B. garinii, B. parkeri, and B. turicatae. These studies demonstrate that binding of human uPA and Pgn to borreliae occurs on multiple species with apparent differences in surface distribution.

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.