Bordetella pertussis binds to human C4b-binding protein (C4BP) at a site similar to that used by the natural ligand C4b

Human complement regulators are important targets for pathogenic microorgan isms. In one such interaction, Bordetella pertussis binds human C4b-binding protein (C4BP), a high-molecular-weight plasma protein that acts as inhibi tor of the classical pathway of complement activation. At least two differe nt B. pertussis surface components, one of which is the virulence factor fi lamentous hemagglutinin (FHA), contribute to the binding. We used a set of C4BP mutants and monoclonal antibodies to characterize the region in C4BP t hat binds B. pertussis and analyzed the salt sensitivity of the Interaction . These studies indicated that positively charged residues at the interface between complement control protein modules 1-2 in the C4BP alpha -chain ar e important for binding, and that the site in C4BP that binds B. pertussis is very similar, but not identical, to the C4b-binding site. Bacteria-bound C4BP retained its complement regulatory function and B. pertussis selectiv ely bound C4BP in human plasma, indicating that binding occurs also in vivo . Together, these findings indicate that B. pertussis exploits a site in C4 BP, resembling that used by the natural ligand C4b.