Studies on the pathogenesis of cholera and salmonella infections suggest that bacterial flagella may be more important than just serving as structures of motility. Campylobacter flagellin, the major protein of the flagella filament, is the major immunodominant protein of Campylobacter jejuni in patients will campylobacter enteritis. The role of campylobacter flagellin in the pathogenesis of campylobacter infection is unclear, however, recent studies suggest that the flagellin may possess an adhesin that could play a role in the interaction with the intestinal mucosa. Epidemiologic and limited volunteer challenge studies show that there is immunity after infection suggesting that some component of C. jejuni, and perhaps flagellin, may be useful for immunoprotection. The specific goals of this proposal are to define biochemically and immunologically some of the antigenic epitopes of campylobacter flagellin and to characterize biologically the nature of antibodies to these determinants. We will study the structure of antigenic epitopes by chemical and enzymatic degradation and immunoblot analysis. We will determine the composition, amino acid sequence (s), and lability of these epitopes by chemical and enzymatic methods to determine the minimal structural requirements for antigenic activity. We will synthesize these epitopes using solid- phase peptide synthesis to further characterize these epitopes and for use in characterizing the human antibody response. The function of flagellin epitopes will be studied by preparing labeled synthetic peptides and assessing the role of these epitopes as adhesins. Finally, we will assess the biological significance of human antibodies directed against these epitopes (i.e. immobilizing activity, bactericidal, inhibition of adherence) by isolating specific antibody through the use of immunoabsorbent columns prepared with synthetic peptides. This information should lead to a tetter understanding of the role of flagellin during infection and may suggest strategies for immunoprotection.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Bacteriology and Mycology Subcommittee 1 (BM)
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University of Pennsylvania
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Nachamkin, I; Fischer, S H; Yang, X H et al. (1994) Immunoglobulin A antibodies directed against Campylobacter jejuni flagellin present in breast-milk. Epidemiol Infect 112:359-65
Nachamkin, I; Yang, X H; Stern, N J (1993) Role of Campylobacter jejuni flagella as colonization factors for three-day-old chicks: analysis with flagellar mutants. Appl Environ Microbiol 59:1269-73
Nachamkin, I; Yang, X H (1992) Local immune responses to the Campylobacter flagellin in acute Campylobacter gastrointestinal infection. J Clin Microbiol 30:509-11
Fischer, S H; Nachamkin, I (1991) Common and variable domains of the flagellin gene, flaA, in Campylobacter jejuni. Mol Microbiol 5:1151-8
Aguero-Rosenfeld, M E; Yang, X H; Nachamkin, I (1990) Infection of adult Syrian hamsters with flagellar variants of Campylobacter jejuni. Infect Immun 58:2214-9
Nachamkin, I; Yang, X H (1989) Human antibody response to Campylobacter jejuni flagellin protein and a synthetic N-terminal flagellin peptide. J Clin Microbiol 27:2195-8