This research proposal focuses on the host-parasite interrelationships of Treponema pallidum and the eucaryotic host. Specifically, studies are concentrated on the attachment of T. pallidum through treponemal adhesions designated proteins, P1, P2 and P3 to human fibronectin and other specialized host proteins. Emphasis will be placed on defining at the molecular level the recognition event between the trial of treponemal adhesins and the arginine-glycine-aspartic acid locus of eucaryotic receptor macromolecules. This study will require the sequencing of structural genes of the treponemal adhesins, the identification and isolation of host receptors, and in order to pinpoint structure-function relationships, the deliberate alteration of the adhesion structural genes to interfere with the receptor- ligand reactions. One of the objectives of the proposal is to identify specific treponemal protein sequences that are vaccine candidates. Rational peptide vaccine candidates will be synthesized and tested by the generation of attachment-blocking antibodies and in vivo assays in the rabbit model. In addition, adhesin-related gene probes will be used to examine the genomic DNA of other spirochetes including street strains derived from syphilitic patients in order to correlate the commonality of adhesin-related gene sequences with virulence potential. It is expected that information obtained from detailed studies of tissue, cell and molecular targeting of T. pallidum will result in a significantly better understanding of the pathobiology and pathogenesis of syphilis and related infections and ultimately lead to interventions for the prevention of the disease.
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