Candida albicans causes a severe esophagitis in patients with acquired immunodeficiency syndrome (AIDS). However, virulence factors associated with the fungus are not understood. Here, the cell wall mannoprotein (mannan) will be studied for its potential as a virulence factor. Mutants of C. albicans will be produced and selected, either by use of antibody specific for mannan, or by tritiated mannose suicide selection. The mannans of the mutants will be characterized chemically and for their ability to activate complement. The mutants will be studied for their adherence to rat esophageal cells in culture, and to rat and human esophageal explants. An attempt will be made to clone genes encoding GDP-mannosyl transferases involved in mannoprotein synthesis. This would allow the enzymes to be studied independently as potential targets for antifungal chemotherapy. These studies should show whether mannan is an important ligand for yeast attachment to esophageal cells and whether subtle alterations in its structure can give rise to changes in complement activation and in adhesion to target cells. The gene cloning technology, used in this research, will lead to future studies aimed at identifying other factors associated with the pathogenesis of C. albicans in AIDS.
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