The long-term objective of our studies is to understand the ability of the pathogenetic human trichomonads to parasitize host cells and tissues in order to increase our knowledge of the chronic nature and pathobiochemistry of trichomoniasis. Our current research proposal is aimed at dissecting the nature of the highly specific recognition events between Trichomonas vaginalis and vaginal epithelial cells and basement membranes. This area of research is highly relevant as the ability to attach to host cells and tissues is the key to urogenital infection and pathogenesis. It is likely at this work will result in identification of adhesin-peptide virulence factors. The specific parasite molecules then are a basis for immunologic or pharmacologic disease intervention strategies. The research will be divided into four separate but related areas. Part I of our grant is aimed toward isolation and characterization of trichomonad surface proteins which are responsible for the receptor-ligand parasitism of epithelial cells. Part II builds upon our knowledge of T. vaginalis-host cell interactions and involves ascertaining the biological significance conferred upon T. vaginalis by selective recognition of extracellular matrix fibronectin. In Part III we propose to generate nospecific and monoclonal antibodies to the host epithelial cell- and fibronectin-binding proteins of T. vaginalis. These antibodies will be used for determining the specificity and structure-function properties of the interactions between host and parasite. Finally, antibodies will be used to screen established and future cDNA libraries as presented in Part IV. Recombinant genes and proteins will be important for further dissecting of the parasite-host recognition systems at the molecular level. This research utilizes cellular and molecular biological, biochemical, and immunological techniques and approaches to address an important aspect of the T. vaginalis: host relationship. It is likely that results from these studies will be useful for other pathogenic protozoan model systems where cytadherence is key to establishment and maintenance of infection.
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