This proposal represents a continuation of our studies into the immunobiology of the lipopolysaccharide of Neisseria gonorrhoeae. These studies will be accomplished through the following specific aims. Secretions from men with gonococcal urethritis and secretions and endocervical tissue from females with gonococcal cervicitis will be studied to define the histopathology of gonorrhoeae using electron microscopic methods and to define the antigenic characteristics of lipopolysaccharide present in human gonococcal infection. This will be accomplished using monoclonal antibodies in immunofluorescent, immunoelectron microscopic and ELISA systems. 2) The chemical nature of the gonococcal LPS antigens which are present in human disease and which are targets for the human immune response will be defined. The oligosaccharide chains containing these antigens will be isolated and the chemical constituents of these antigens will be determined. Oligosaccharide chains shown to contain antigens relevant to the human immune response will be conjugated to a variety of gonococcal cell surface proteins including fragments from enzymatic digestion of pilus and protein l. The human immune response to gonococcal lipopolysaccharide will be studied to define the LPS sites against which bactericidal antibody is directed in normal human serum, in patients with genital gonorrhoeae and in patients with gonococcal PID and disseminated infection and to define the evolution of the human immune response to gonococcal LPS which occurs in genital and extra-genital gonococcal infection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI018384-05
Application #
3127891
Study Section
Bacteriology and Mycology Subcommittee 1 (BM)
Project Start
1981-07-01
Project End
1988-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
5
Fiscal Year
1985
Total Cost
Indirect Cost
Name
State University of New York at Buffalo
Department
Type
Schools of Medicine
DUNS #
038633251
City
Buffalo
State
NY
Country
United States
Zip Code
14260
Harvey, H A; Jennings, M P; Campbell, C A et al. (2001) Receptor-mediated endocytosis of Neisseria gonorrhoeae into primary human urethral epithelial cells: the role of the asialoglycoprotein receptor. Mol Microbiol 42:659-72
Long, C D; Hayes, S F; van Putten, J P et al. (2001) Modulation of gonococcal piliation by regulatable transcription of pilE. J Bacteriol 183:1600-9
Harvey, H A; Porat, N; Campbell, C A et al. (2000) Gonococcal lipooligosaccharide is a ligand for the asialoglycoprotein receptor on human sperm. Mol Microbiol 36:1059-70
Zenni, M K; Giardina, P C; Harvey, H A et al. (2000) Macropinocytosis as a mechanism of entry into primary human urethral epithelial cells by Neisseria gonorrhoeae. Infect Immun 68:1696-9
Lee, F K; Gibson, B W; Melaugh, W et al. (1999) Relationship between UDP-glucose 4-epimerase activity and oligoglucose glycoforms in two strains of Neisseria meningitidis. Infect Immun 67:1405-14
Lee, F K; Dudas, K C; Hanson, J A et al. (1999) The R-type pyocin of Pseudomonas aeruginosa C is a bacteriophage tail-like particle that contains single-stranded DNA. Infect Immun 67:717-25
Estabrook, M M; Zhou, D; Apicella, M A (1998) Nonopsonic phagocytosis of group C Neisseria meningitidis by human neutrophils. Infect Immun 66:1028-36
Giardina, P C; Williams, R; Lubaroff, D et al. (1998) Neisseria gonorrhoeae induces focal polymerization of actin in primary human urethral epithelium. Infect Immun 66:3416-9
Harvey, H A; Ketterer, M R; Preston, A et al. (1997) Ultrastructural analysis of primary human urethral epithelial cell cultures infected with Neisseria gonorrhoeae. Infect Immun 65:2420-7
Apicella, M A; Ketterer, M; Lee, F K et al. (1996) The pathogenesis of gonococcal urethritis in men: confocal and immunoelectron microscopic analysis of urethral exudates from men infected with Neisseria gonorrhoeae. J Infect Dis 173:636-46

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