This program project focuses upon questions directly related to Candida infections in AIDS and more generally to virulence factors of the organism. Because the most common form of candidiasis in AIDS is oralpharyneal and/or vaginitis, we will utilize both molecular and biochemical approaches to determine the attributes of Candida albicans which allow it to infect these sites. Equally important, we will focus upon mucosal responses to the organism, specifically both total sIgA and Candida-specific sIga responses. In Project I, two of the putative adhesions of C. albicans are to be purified, the encoding genes isolated, and null mutants in each adhesion constructed. These mutants will then be assayed for virulence in both oral and vaginal animal models.
A second aim of Project I is to determine if signal transduction pathways in Candida are activated during adherence of the organism to human buccal epithelial cells. In Project II, an in vivo expression technology (IVET) system will be developed for C. albicans. Using a rat model of oral candidiasis, potential gene products that contribute to the ability of C. albicans to establish oral infection will be identified. Again, as in Project I, the emphasis is on the interaction of the interaction of the organism with oral mucosa. In Project III, salivary and vaginal fluids from AIDS patients will be analyzed for sIgA responses to Candida. This project will emphasize a longitudinal study of patient responses. Antibody to known immunodominant proteins of Candida, including the adhesions, will be examined. In summary, the goal of this program project is to establish the mechanisms by which this organism can infect oral and vaginal mucosa and to qualitatively and quantitatively measure the antibody responses to the organism during candidiasis in the AIDS patients.
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