Little is understood about the control of virulence in Candida albicans, a fungus that causes a severe ulcerative esophagitis in many AIDS patients. Growth of C. albicans on sucrose or galacose has been shown to cause changes in its cell wall which simulate those found in vivo and, in addition, the same sugars cause an increase in the virulence of this species. Because the direct study of the control of virulence is extremely difficult, the objective of the research proposed will be to define the basic mechanisms involved in the sucrose-modulated control of invertase activity. Invertase is present in large quantities in sucrose-grown cells but appears in only small quantities in cells grown in glucose. Control of expression of the invertase structural gene thereby acts as a model for the control processes used by other sucrose-modulated genes including those directly involved in virulence. The invertase gene will be cloned by complementation of invertase-negative yeasts. After sequencing and comparison to known genes, the control of its expression will be studied in morphological mutants and int he various growth forms of C. albicans. Control of the synthesis of other proteins induced by sucrose will be compared to those induced during the morphological transition from yeast to filamentous form. Changes in virulence will be monitored by studies of yeast attachment to epithelial cells and to fibrin clots and, where appropriate, by studies of the capability of the C. albicans mutants to cause disease in mice. The study will seek evidence for central control mechanisms which affect numerous genes including those involved with virulence.
