Despite a number of stragegies for controlling the high incidence of chlamydia and the fact that an adequate treatment exists for the disease, the reported incidence approaches several million cases a year at an annual cost of approximately $2 billion a year. Control of this disease would be aided if better micobicides were identified which could be topically applied and were effective in either neutralizing the chlamydia prior to attachment or blocking cell receptors on athe surface of genital mucosal epithelium. It is the goal of this proposal to screen a number of compounds including the sulfated polysaccharides, surfactants, detergents, and bile salts for their ability to inhibit attachment and/or infectivity of Chlamydia trachomatis in a variety of model systems. One of the principal objectives of this project is to identify those antichlamydial agents which are effective in preventing infection of human cell and organ culture models. The cultured cells will include those cells routinely used for chlamydial infectivity studies (polarized an nonpolarized HeLa cell monolayers) as well as the recently described human fallopian tube organ culture of C. trachomatis infection.
The specific aims are: (1) to determine the antichlamydial activity and cellular cytoxicity of a selected group of microbicidal compounds in cell and organ culture systems and (2) to determine the molecular interaction between the microbicide activity and the ligand epitope on the genital mucosal epithelium. Successful antichlamydial microbicidal agents identified in this project will also be used in project 3 for studies designed to define the determinants of chlamydial pathogenesis int he guinea pig model. The information that will be obtained in all of the projects in this proposal will aid in the identification of microbicides that are effective in protecting cells and tissues of the human female genital tract against sexually transmitted viral and bacterial pathogens.
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