Lyme borreliosis is now the most common arthropod-borne disease in the United States and Europe. It is caused by Borrelia burgdorferi, a tickborne spirochete that is related to the agents of relapsing fever. B. burgdorferi infection of adults and children is often complicated by chronic and disabling arthritis or neurologic disease. The immune response to the infection is characterized by the slow appearance of antibodies to abundant outer membrane proteins, known as Osp proteins, and by what may be an overly vigorous and self-injurous cell-mediated reaction. The role of spirochete components and virulence factors in either avoiding the antibody response or eliciting pathologic changes in the host is of interest. There is evidence of antigenic variation by B. burgdorferi both in vitro and in vivo. Study of diversity between strains and of antigenic variation of modulation within a strain may reveal critical factors in the pathogenesis of complicated Lyme borreliosis. Such a study may also identify potential vaccine candidates as well as reagents for improved diagnostic assays. The project will use a molecular genetic approach and will examine differences between strains and variants down to and including the level of the genome. The first specific aim of this project is characterization of differences between strains in their Osp and other surface proteins, in the structural protein of the spirochete's periplasmic flagella, and in a major 60K antigen. The second specific aim is determination of the mechanism of antigenic variation in B. burgdorferi. Important to this part of the study will be an investigation of the regulation of gene expression in B. burgdorferi.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI029731-02
Application #
3144638
Study Section
Special Emphasis Panel (SRC)
Project Start
1990-04-01
Project End
1995-03-31
Budget Start
1991-04-01
Budget End
1992-03-31
Support Year
2
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Texas Health Science Center San Antonio
Department
Type
Schools of Medicine
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229
Noppa, L; Burman, N; Sadziene, A et al. (1995) Expression of the flagellin gene in Borrelia is controlled by an alternative sigma factor. Microbiology 141 ( Pt 1):85-93
Sadziene, A; Thomas, D D; Barbour, A G (1995) Borrelia burgdorferi mutant lacking Osp: biological and immunological characterization. Infect Immun 63:1573-80
Sadziene, A; Jonsson, M; Bergstrom, S et al. (1994) A bactericidal antibody to Borrelia burgdorferi is directed against a variable region of the OspB protein. Infect Immun 62:2037-45
Cadavid, D; Thomas, D D; Crawley, R et al. (1994) Variability of a bacterial surface protein and disease expression in a possible mouse model of systemic Lyme borreliosis. J Exp Med 179:631-42
Simpson, W J; Cieplak, W; Schrumpf, M E et al. (1994) Nucleotide sequence and analysis of the gene in Borrelia burgdorferi encoding the immunogenic P39 antigen. FEMS Microbiol Lett 119:381-7
Carter, C J; Bergstrom, S; Norris, S J et al. (1994) A family of surface-exposed proteins of 20 kilodaltons in the genus Borrelia. Infect Immun 62:2792-9
Shoberg, R J; Jonsson, M; Sadziene, A et al. (1994) Identification of a highly cross-reactive outer surface protein B epitope among diverse geographic isolates of Borrelia spp. causing Lyme disease. J Clin Microbiol 32:489-500
Sadziene, A; Thompson, P A; Barbour, A G (1993) In vitro inhibition of Borrelia burgdorferi growth by antibodies. J Infect Dis 167:165-72
Erdile, L F; Brandt, M A; Warakomski, D J et al. (1993) Role of attached lipid in immunogenicity of Borrelia burgdorferi OspA. Infect Immun 61:81-90
Sadziene, A; Barbour, A G; Rosa, P A et al. (1993) An OspB mutant of Borrelia burgdorferi has reduced invasiveness in vitro and reduced infectivity in vivo. Infect Immun 61:3590-6

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