Abstracts (complete list) - Wissenschaft Online

Evelyn Rossmann, Peter Kraiczy, Pia Herzberger, Christine Skerka, Michael Kirschfink,
Markus M. Simon, Peter F. Zipfel, Reinhard Wallich
BhCRASP-1 of the relapsing fever spirochete Borrelia hermsii
is a factor H and plasminogen binding protein
Borrelia (B.) hermsii is the most frequent tick-borne relapsing fever agent in North
America and is transmitted to humans through the bites of infected Ornithodoros ticks.
B. hermsii employs several mechanisms to persist in the blood and evade immune
response. Antigenic variation is clearly important to escape humoral immunity.
Complement may be more important in opsonization and phagocytosis. Here we
identified a novel member of the complement regulator acquiring surface protein
(CRASP) family expressed by B. hermsii and designated BhCRASP-1. The ability to bind
the complement regulators, factor H (FH) and factor H related protein 1 (FHR-1) but not
FH-like protein 1 (FHL-1) has important implications for the host-pathogen interaction.
In this study, we demonstrate that pathogens that bind FH exploit the regulatory
activity of this protein, which serves to control C3b deposition and C3 convertase
activity. BhCRASP-1 specifically interacts with the short consensus repeat 20 of FH.
Heterologous expression of BhCRASP-1 in the serum-sensitive B. burgdorferi B313
strain protects transformed B313 cells to some extent from complement-mediated
killing. Furthermore, we show that FH and plasminogen can bind concurrently to
BhCRASP-1, however via distinct, non-overlapping domains. Binding of plasminogen to
BhCRASP-1 in the presence of host-derived urokinase-type plasminogen activator (uPA)
leads to the formation of active plasmin that degrades high molecular weight
glycoproteins, such as fibrinogen. Our findings will be helpful to further elucidate the
molecular basis of B. hermsii interactions with host factors in the pathogenesis of
relapsing fever.