Date of Award

8-2015

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Major

Microbiology

Major Professor

Todd B. Reynolds

Committee Members

Jeffrey M. Becker, Timothy Sparer, Gladys Alexandre, Chunlei Su

Abstract

In hospitalized patients with neutropenia, Candida albicans is the fourth leading cause of systemic bloodstream infections, which have a mortality rate of approximately 30 %. The phosphatidylserine synthase enzyme of C. albicans, Cho1p, appears to be a good drug target as a mutant lacking this enzyme (the cho1Δ/Δ [null mutant]) is avirulent in animal models of Candida infections and this enzyme is not conserved in humans. We discovered that the loss of phosphatidylserine (PS) synthesis affects C. albicans' expression of the Als3p adhesin, a virulence protein, and loss of PS synthesis also compromises the cell wall, causing increased exposure of the polysaccharide β [beta]-(1,3) glucan that ultimately leads to increased recognition by the immune system.

Downstream of phosphatidylserine synthase are the decarboxylase enzymes Psd1p and Psd2p, which are essential for de novo synthesis of phosphatidylethanolamine from phosphatidylserine. When these enzymes are lost, the only option the yeast has to acquiring phosphatidylethanolamine is by synthesizing it by the Kennedy Pathway utilizing ethanolamine acquired from the environment. The final chapter of my dissertation explores how ethanolamine is difficult to acquire from the host in vivo, and is ultimately a bottleneck for C. albicans to cause virulence in the mouse model of disseminated candidiasis.

Hyphal_extension_Wild_Type.mp4 (1422 kB)
Video A1. Measurement of hyphal length via time lapse microscopy for WT.

Hyphal_extension_cho1.mp4 (1420 kB)
Video A2. Measurement of hyphal length via time lapse microscopy for the cho1Δ/Δ mutant.

Hyphal_extension_psd1.mp4 (1475 kB)
Video A3. Measurement of hyphal length via time lapse microscopy for the psd1Δ/Δ mutant.

Hyphal_extension_psd1_psd2.mp4 (1452 kB)
Video A4. Measurement of hyphal length via time lapse microscopy for the psd1Δ/Δ psd2Δ/Δ mutant.

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

Share

COinS