A number of key virulence factors of Candida albicans are encoded by glycosyl-phosphatidylinositol- anchored proteins (GPI-proteins). Amongst these virulence associated GPI-proteins are those that regulate morphogenesis, adherence to and/or invasion of host cells, and resistance to phagocyte-mediated killing. In the studies proposed herein, we will use an innovative, function-based approach to investigate the pathogenesis of C. albicans by identifying unique, surface GPI-proteins that encode virulence associated phenotypes. We will: 1) over-express putative GPI-proteins identified by the C. albicans sequencing project using the tetracycline regulated promoter; and 2) identify C. albicans GPI-proteins responsible for seven virulence associated phenotypes through """"""""gain/increase-of-function"""""""" screening. This new, complementary approach overcomes phenotypic unavailability, functional redundancy, and essential gene problems that plague gene disruption approaches. It also greatly facilitates large-scale functional screening. Because these GPI-proteins are localized on the Candida cell surface, results will yield potential avenues for future research and provide important insights into the pathogenesis of the organism and host-pathogen interaction. Additionally, GPI-proteins are easily accessible to drugs, and therefore may reveal promising new targets for therapeutic interventions against C. albicans infections. ? ? ?
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