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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI038415-01A1
Application #
2004324
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Project Start
1997-01-01
Project End
2000-12-31
Budget Start
1997-01-01
Budget End
1997-12-31
Support Year
1
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Cincinnati
Department
Genetics
Type
Schools of Medicine
DUNS #
City
Cincinnati
State
OH
Country
United States
Zip Code
45221
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