The object of the proposed research is to understand the genetic and molecular nature of microbial determinants that contribute to the pathogenesis of Bordetella pertussis infection and disease. Cloned Bordetella DNA sequences have been isolated encompassing the operon, Vir, which specifies a trans-acting inducer required for the coordinate expression of the genes associated with B. pertussis virulence. We propose to define this gene by genetic crosses and characterize the Vir gene product(s). In addition, we have successfully cloned and expressed genes specifying the B. pertussis filamentous hemagglutinin (Fha) in E. coli K-12 as well as the gene(s) specifying pertussis toxin. These virulence determinants will be characterized genetically, and their products examined by in vitro biosynthetic models and by DNA sequencing. We have, in addition, devised a simple method to return modified, cloned genetic sequences from E. coli K-12 back to Bordetella. By this means, we propose to precisely determine the regulatory mechanism of Vir as well the precise contribution of the virulence determinants to the pathogenesis of infection as well as the severe encephalopathy which is occasionally associated with current pertussis immunization.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AI023945-08
Application #
3481276
Study Section
Special Emphasis Panel (NSS)
Project Start
1986-07-01
Project End
1996-04-30
Budget Start
1993-05-01
Budget End
1994-04-30
Support Year
8
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Stanford University
Department
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305