BORDETELLA-PERTUSSIS BINDS THE HUMAN-COMPLEMENT REGULATOR C4BP - ROLEOF FILAMENTOUS HEMAGGLUTININ

C4BP (C4b-binding protein) is a high-molecular-weight plasma protein t hat inhibits the classical pathway of complement activation, Recent ex periments have demonstrated that C4BP binds to many strains of the gra m-positive bacterium Streptococcus pyogenes, a major respiratory tract pathogen, Binding to S, pyogenes was shown to be due to members of th e M protein family, a group of surface proteins important for virulenc e. Here we report that human C4BP also binds to all clinical isolates of the gram-negative bacterium Bordetella pertussis, the etiologic age nt of whooping cough. In addition, binding of C4BP was demonstrated fo r other Bordetella species that can cause disease in humans. Character ization of different B. pertussis mutants showed that the binding of C 4BP is strongly dependent on the expression of the cell surface protei n filamentous hemagglutinin, a well-known virulence factor, Inhibition experiments suggested that B. pertussis and S. pyogenes bind to the s ame region in C4BP. The finding that B. pertussis and S. pyogenes both have the ability to bind human C4BP suggests that these two unrelated respiratory tract pathogens may use a common mechanism during the est ablishment of an infection.