The prevalence of the protozoan, Trichomonas vaginalis, as a leading sexually transmitted disease agent and as the number one parasitic infection in our country and possibly the world, requires that the widely- reported antigenic diversity among trichomonal isolates be understood at the molecular biological level. Only in this way will interference strategies be developed for control of this disease. This proposal has as its central theme the study of three T. vaginalis specific genes and their corresponding proteins. The proteins contribute to the antigenic heterogeneity of the pathogenic human trichomonads. Accordingly, the proposal is divided into three separate yet interrelated areas as summarized below, which are bridged by the molecular biological, biochemical, and immunological technologies used for characterization of the genes and corresponding proteins.
Specific Aim 1 will involve the molecular characterization of the immunogen, called P270, which undergoes phenotypic variation with respect to surface expression only among some isolates. Evidence points toward a single epitope, tandemly repeated at the DNA level, for this high molecular weight protein.
Specific Aim 2 will continue investigation of a gene encoding the entire structural protein, which is uniquely expressed among the isolates comprised of trichomonads which undergo phenotypic variation. The gene for this protein, called P55, is present in multiple copies among all isolates, however, suggesting that specific regulation of gene expression occurs only among some isolates.
Specific Aim 3 intends to begin the characterization of a protein, called P230, which is found on the surface of all trichomonads. Antibody only to this protein is found in the vagina of patients with trichomoniasis, making this immunogen highly relevant to infection, and possibly pathogenesis. The focused study bringing together the molecular-recombinant DNA and protein biochemistry techniques to study three specific genes and their products is proposed for the first time for this important protozoan parasite. The use of an integrated, interdisciplinary approach involving these molecules will lead to a greater understanding of several important biological properties of this pathogen, such as the molecular organization of the parasite's genome, commonality/diversity of trichomonads at the DNA level, regulation of gene expression, and the contribution of specific molecules to infection and pathogenesis. These are the long-term, broad objectives of the overall program. Finally, this project is a vehicle for the education of pre- and postdoctoral trainees in STDs in general and T. vaginalis in particular.
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