Doctoral Dissertations

Date of Award

5-2009

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Major

Microbiology

Major Professor

Todd Reynolds

Abstract

Candida albicans is a major human fungal pathogen. A primary goal in studying C. albicans virulence is actually to find the ways to undermine it and prevent disease. The best drug targets are proteins or molecules that are not conserved in humans. For most antimicrobials against bacteria, fungi, or protozoans, the targets are not virulence factors, but rather enzymes that are important for basic growth or survival. It is not imperative that the target be required in all growth conditions, but rather just in the host. An area of research that has shown promising potential for the discovery of new drug targets in several microbal pathogens is in phospholipid biosynthesis. In this dissertation, there are three projects that revolve around studying proteins that may be potential drug targets for C. albicans. 1) inositol biosynthesis was examined.It has been shown in the pathogens Mycobacterium tuberculosis and Trypanosoma brucei that de novo inositol biosynthesis is required for virulence or growth. Therefore, the enzyme required for de novo inositol synthesis was examined for a role in virulence. 2) The phosphatidylserine (PS) synthase gene (CHO1) of S. cerevisiae is conserved in other fungi, and is not conserved in humans. Given that PS is an abundant phospholipid in yeasts, it was hypothesized that it would be important for virulence in the host. 3) Fungi carry homologs of a fungal-specific transcription factor, called Opi1p, that has been shown to be involved in regulating filamentous growth and phospholipid biosynthesis in S. cerevisiae. Its homolog was examined in C. albicans to determine if it regulated these phenotypes in this pathogen because filamentous growth is an important virulence factor.If the CaOpi1p protein were essential for filamentous growth then it might be good drug target as it is not conserved in humans. All three of these projects revolve around phospholipid biosynthesis in C. albicans and each has revealed interesting and sometime surprising aspects of the biology and virulence of this fungus.

Download
Files over 3MB may be slow to open. For best results, right-click and select "save as..."

Share

COinS