The effect of perturbing membrane biogenesis on yeast cell germination and chitin biosynthesis will be studied in Candida albicans. Our approach in investigating these issues will be to dissect the steps leading to germination by employing agents that inhibit the process. In particular, we will utilize the antilipogenic agent, cerulenin, to manipulate the phospholipid and sterol composition of membrane-containing structures, and then determine the effect of such changes on morphogenesis. Sodium butyrate, an agent that does not directly influence lipid biosynthesis, will be employed as an alternative inhibitor of Candida albicans germination, so that we may distinguish between events inhibited by cerulenin that are correlates of morphogenesis from those events only coupled to inhibition of lipid biosynthesis. In addition, several cerulenin-resistant C. albicans mutant strains have been isolated. These strains will be exploited directly, and will also be utilized as experimental controls, where appropriate. Preliminary experiments have shown that both cerulenin and butyrate effectively block germination and inhibit chitin synthase activity in C. albicans at concentrations that do not significantly affect yeast cell growth or protein synthesis. We will now extend these studies utilizing biochemical and molecular techniques to: 1) Examine the relationship between membrane structure, chitin synthase regulation and activity, and germination. 2) Determine the influence of the membrane phospholipid/sterol composition on membrane and cell wall proteins, as will as on cell surface components. 3) Examine factors that may influence adherence properties of Candida. 4) Assess the contribution of mitochondria to Candida germination. These investigations will provide insight concerning both dimorphism and pathogenesis of C. albicans.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE007168-02
Application #
3220694
Study Section
Bacteriology and Mycology Subcommittee 1 (BM)
Project Start
1984-08-01
Project End
1987-07-31
Budget Start
1985-08-01
Budget End
1986-07-31
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Georgetown University
Department
Type
School of Medicine & Dentistry
DUNS #
049515844
City
Washington
State
DC
Country
United States
Zip Code
20057