The first defense of the oral cavity against fungal and bacterial agents is afforded by salivary immune and nonimmune proteins. Recent evidence points to an increasing importance of the nonimmune oral defense system exhibited by proteins synthesized in parotid and submandibular/sublingual glands. The applicant has discovered a new class of anionic salivary proteins demonstrating antifungal effects by either killing or inhibiting the adhesion of the fungal pathogen, Candida albicans. This organism is the major pathogen causing candidiasis in the oral cavity. Oral candidiasis is particularly prevalent as a secondary infection in HIV infected individuals and AIDS patients. The goal of this application is to gain insights into the structure/function relationships of the newly discovered antifungal salivary proteins.
The specific aims of this project are to: 1. isolate and characterize anionic salivary anticandidal proteins in terms of their composition and primacy structure; 2. determine the complete primary structures of these proteins from the deduced amino acid sequences of their cDNAs in order to identify sequences representing functional domains; 3. functionally characterize these proteins using anticandidal assays to measure killing of blastoconidia, inhibition of germination, killing of germinated cells, and inhibition of adhesion to buccal epithelial cells; 4. express functional domains of these proteins using recombinant DNA technology and examine their antifungal activity spectrum.
