Abstract

Gonorrhea remains one of the most common infectious diseases and eludes control by means other than vaccination. For a meaningful immunoprophylactic program, information on the structure-function relationship of the surface antigens with host components are needed. The proposed work consists of determining the primary structure of proteins I, proteins II, and pili by standard DNA and protein sequencing techniques. Currently available cloned genes will be used and additional ones will be isolated by hybridization selection with the cloned genes already available, with synthetic oligonucleotides, and by immunological selection of clones expressing the product. The genetic mechanisms responsible for intra-strain variability of proteins II will be studied with DNA probes to variable and constant areas of the molecule. The folding of protein I will be studied with bifunctional reagents, and its secondary and tertiary structure elucidated by spectroscopic and X-ray diffraction techniques. The steps involved in pilin assembly into fully formed pili will be studied by chemical and genetic techniques. The ligand on human cells binding to gonococcal pili will be defined.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI010615-16
Application #
3124737
Study Section
Bacteriology and Mycology Subcommittee 1 (BM)
Project Start
1974-09-01
Project End
1989-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
16
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
Rockefeller University
Department
Type
Graduate Schools
DUNS #
071037113
City
New York
State
NY
Country
United States
Zip Code
10065

  Publications

Gotschlich, E C (1994) Genetic locus for the biosynthesis of the variable portion of Neisseria gonorrhoeae lipooligosaccharide. J Exp Med 180:2181-90
Erwin, A L; Gotschlich, E C (1993) Oxidation of D-lactate and L-lactate by Neisseria meningitidis: purification and cloning of meningococcal D-lactate dehydrogenase. J Bacteriol 175:6382-91
Wetzler, L M; Blake, M S; Barry, K et al. (1992) Gonococcal porin vaccine evaluation: comparison of Por proteosomes, liposomes, and blebs isolated from rmp deletion mutants. J Infect Dis 166:551-5
Weiser, J N; Gotschlich, E C (1991) The role of outer membrane protein A in Escherichia coli K-1 pathogenesis. Trans Assoc Am Physicians 104:278-84
Koomey, M; Bergstrom, S; Blake, M et al. (1991) Pilin expression and processing in pilus mutants of Neisseria gonorrhoeae: critical role of Gly-1 in assembly. Mol Microbiol 5:279-87
Weiser, J N; Gotschlich, E C (1991) Outer membrane protein A (OmpA) contributes to serum resistance and pathogenicity of Escherichia coli K-1. Infect Immun 59:2252-8
Butler, C A; Gotschlich, E C (1991) High-frequency mobilization of broad-host-range plasmids into Neisseria gonorrhoeae requires methylation in the donor. J Bacteriol 173:5793-9
Blaser, M J; Gotschlich, E C (1990) Surface array protein of Campylobacter fetus. Cloning and gene structure. J Biol Chem 265:14529-35
Blake, M S; MacDonald, C M; Klugman, K P (1989) Colony morphology of piliated Neisseria meningitidis. J Exp Med 170:1727-36
Murakami, K; Gotschlich, E C; Seiff, M E (1989) Cloning and characterization of the structural gene for the class 2 protein of Neisseria meningitidis. Infect Immun 57:2318-23

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