Although pertussis remains a world-wide problem, whole-cell and acellular vaccines appear to induce short-lived immunity but do not prevent infection by the bacterium. The host with waning immunity may thereby serve as a reservoir for the infection of others. A novel bacterial virulence mechanism within the bvg locus of the B. pertussis genome, Brk, controls resistance to killing by the classical antibody-dependent pathway of complement. BrkA inhibits membrane attack complex formation at C5 by inhibiting C5 activation or deposition.
In Specific Aim 1, the size of the BrkA protein will be determined by N-terminal sequencing and its surface location will be defined by immunoelectron or immunofluorescent studies.
In Specific Aim 2, the region of BrkA responsible for serum resistance will be defined with the use of fusion proteins and truncation or deletion mutants. The BrkA resistance mechanism will be characterized by differentiating the effects of brkA on C5 activation or deposition and by identifying human proteins that interact with the BrkA fusion protein.
Showing the most recent 10 out of 11 publications
