BhCRASP-1 of the relapsing fever spirochete Borrelia hermsii is a factor H- and plasminogen-binding protein

The spirochete Borrelia (B.) hermsii is the most frequent tick-borne relapsing fever agent in North America. B. hermsii organisms employ multiple strategies, including acquiring complement regulators and antigenic variation to escape innate and humoral immunity, respectively. Here, we identified a novel member of the complement regulator-acquiring surface protein (CRASP) family, designated BhCRASP-1, that binds the complement regulators, factor H (FH) and FH-related protein 1 (FHR-1) but not FH-like protein 1 (FHL-1). We show that FH when bound to BhCRASP-1 maintains its regulatory capacity to control C3b deposition and C3 convertase activity. BhCRASP-1 specifically interacts with the short consensus repeat 20 of FH, thereby maintaining FH-associated cofactor activity for factor I-mediated C3b inactivation. Heterologous expression of BhCRASP-1 in the serum-sensitive B. burgdorferi B313 strain protects transformed cells from complement-mediated killing, at least partially. Furthermore, we show that BhCRASP-1 concurrently binds plasminogen in addition to FH, however, via distinct, non-overlapping domains. Our findings will be helpful to further elucidate the molecular basis of B. hermsii interactions with host factors in the pathogenesis of relapsing fever.