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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI021947-03
Application #
3132470
Study Section
(SSS)
Project Start
1984-09-30
Project End
1987-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Toledo
Department
Type
Schools of Medicine
DUNS #
807418939
City
Toledo
State
OH
Country
United States
Zip Code
43614
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Lehmann, P F; Donabedian, H; Sawyer, T (1987) Expansion of a T lymphocyte subpopulation (CD3+,4-,8-) after immunodepression associated with disseminated histoplasmosis. Int Arch Allergy Appl Immunol 84:311-5
Lehmann, P F (1985) Immunology of fungal infections in animals. Vet Immunol Immunopathol 10:33-69