Urinary tract infections (UTI) caused by Escherichia coli are among the most common bacterial diseases, yet little is known about the pathogenic mechanisms involved. Previous work has shown that adhesion of these bacteria to host epithelium via the P blood group antigen receptor is an important virulence determinant. The pyelonephritis-associated pili (pap) gene cluster has been shown to encode P-adhesion activity as well as pilin monomers that polymerize at the bacterial cell surface to form pili fibers. Genetic evidence indicates that pilin and adhesin protein(s) may interact to form an """"""""adhesin structure"""""""". However, the role(s) of each pap-encoded protein in forming this postulated structure and in adherence are not known. The studies proposed here are designed to provide information regarding the molecular mechanism(s) by which these bacteria that cause UTI adhere to host cells. My approach will be to first generate antisera to pap- encoded gene products that appear to play roles in adhesion. Antisera will be generated to partially-purified protein isolated from E. coli strains over-producing these proteins. These antisera and antisera I have already generated to pap-encoded pili will be used to determine the cellular location(s) of each pap-encoded protein. An important part of these studies will be the analysis of strains containing non-polar insertions within each of the pap genes. By analyzing the effect(s) of these mutations on the interactions between pap-encoded pilin and adhesin-associated proteins, the pathway for assembly of these gene products into an adhesin structure will be determined. The interactions between these pap proteins to form an adhesin structure will be determined by using colloidal gold-tagged anti-pap protein antisera and electron microscopy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Modified Research Career Development Award (K04)
Project #
5K04AI000881-02
Application #
3070923
Study Section
Bacteriology and Mycology Subcommittee 1 (BM)
Project Start
1988-06-01
Project End
1993-05-31
Budget Start
1989-06-01
Budget End
1990-05-31
Support Year
2
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Utah
Department
Type
Schools of Medicine
DUNS #
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
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