Candida albicans is a member of the indigenous human flora and is responsible for the largest percentage of oral and esophageal infection of fungal origin in uncompromised individuals, and is of increasing concern in individuals compromised by immunodeficiencies resulting from disease or therapies. While several putative C. albicans virulence factors have been identified that may contribute to oral candidiasis, efforts to detect others suffer from the inherent problem of utilizing cells prepared in a laboratory environment to distinguish gene products which may only be expressed in an infected host. In this regard, a powerful new genetic technique, termed in vivo expression technology (IVET), has been reported that, when applied to C. albicans, may overcome this problem. Thus, the primary aim of this project is to determine the feasibility of developing a suitable IVET system for use in identifying potential gene products that contribute to the ability of C. albicans to establish oral infection. The ingredients required to design such a system are either available or can be constructed, and these include an animal model for oral candidiasis, appropriate isogenic virulent and avirulent C. albicans strains, and suitable plasmid cloning vehicles. The strategy will be to develop and then integrate these components into an effective IVET test model. After the efficacy of the system has been determined, efforts will turn to the isolation and characterization of genes encoding factors required for the establishment and progression of C. albicans mediated infections.
