- Collection:
- Atlanta University and Clark Atlanta University Theses and Dissertations
- Title:
- Effects of inhibitors of proteins in the ras signaling pathway on the formation of filaments in Ccandida Albicans, 2004
- Creator:
- Bernoudy, Geneva C.
- Date of Original:
- 2004-05-01
- Subject:
- Degrees, Academic
Dissertations, Academic - Location:
- United States, Georgia, Fulton County, Atlanta, 33.749, -84.38798
- Medium:
- theses
- Type:
- Text
- Format:
- application/pdf
- Description:
- Candida albicans is a fungus that may cause mild to fatal infections in people with compromised immune systems. Patients undergoing chemotherapy or radiation therapy as a result of cancer, or those infected with AIDS, frequently develop Candida infections. Candida albicans is part of the normal human flora, but invasive or deep Candidiasis is usually fatal and the less serious forms are often persistent and recurring. C. albicans exists as cellular yeast, or benign budding form, and as a filamentous form. The filamentous form is associated with pathogenicity and has the ability to penetrate tissues. This transformation appears to be controlled by the Ras protein. In vitro, filament formation can be caused by serum induction or nitrogen starvation. Ras proteins are small GTP-binding proteins involved in signal transduction. Ras proteins are post translationally prenylated. Prenylation of Ras involves the addition of a famesyl group at a cysteine residue localized four amino acids from the C-terminus. It is then modified by removal of the last three amino acids and methylation of the newly exposed famesyl-cysteine residue. Ras is considered to be inactive if it is not prenylated. If Ras prenylation is blocked it may prevent the formation of filamentous Candida albicans. The objective of this study is to determine which proteins in Ras signaling pathway are important for the formation of filaments. In the presence of inhibitors of the mevalonate, alternative IPP, and MAPK pathways, C. albicans cells were grown on solid media (YPD and spider) for four days. These results show that an inhibitor of the alternative IPP pathway caused little or no effect on the growth of C. albicans or on the formation of filaments. On the other hand, Mevastatin, an inhibitor of the mevalonic acid pathway to IPP, caused significant inhibition of both growth and the formation of filaments. An inhibitor of MEK, a protein in the MAP-Kinase pathway, caused little or no inhibition of growth of C. albicans but caused some inhibition of filament formation at higher concentrations. This MEK inhibitor does not appear to completely inhibit yeast to filament transformation.
- External Identifiers:
- Metadata URL:
- http://hdl.handle.net/20.500.12322/cau.td:2004_bernoudy_geneva_c
- Rights Holder:
- Clark Atlanta University
- Holding Institution:
- Atlanta University Center Robert W. Woodruff Library
- Rights:
-
