Molecular Characterization of the Interaction ofBorrelia parkeriandBorrelia turicataewith Human Complement Regulators

Abstract

ABSTRACTIn North America, tick-borne relapsing fever is caused by the speciesBorrelia hermsii,B. parkeri, andB. turicatae, which are transmitted to humans through the bite of the respective infected tick vectors. Here we describe the identification and functional characterization of a surface lipoprotein ofB. parkeri, designated BpcA, that binds the human complement regulators factor H and factor H-related protein 1 and, simultaneously, the host protease plasminogen. In contrast, the homologousB. turicataeprotein failed to bind human factor H and factor H-related protein 1 but retained its plasminogen binding capacity. Factor H bound to BpcA maintains its regulatory capacity to control C3b deposition and C3 convertase activity. Ectopic expression of BpcA in a serum-sensitiveB. burgdorferistrain protects transformed cells from complement-mediated killing. Furthermore, bound plasminogen/plasmin endowsB. parkeriandB. turicataewith the potential to degrade extracellular matrix components. These findings expand our understanding of the putative recent evolutionary separation ofBorrelia parkeriandBorrelia turicatae, provide evidence thatB. parkeridiffers fromB. turicataein its ability to resist complement attack, and may help in understanding the pathological processes underlying tick-borne relapsing fever.