Date of Award

12-2012

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Major

Microbiology

Major Professor

Todd Reynolds

Committee Members

Jeffrey Becker, Timothy Sparer, Gladys Alexandre, Erik Zinser

Abstract

Enzymes involved in phospholipid biosynthesis have been suggested as possible drug targets to treat Candida albicans infections because several key enzymes, such as phosphatidylserine synthase, differ from those of the human host.We have found that phosphatidylserine synthase of C. albicans is required for virulence in a mouse model of systemic Candida infection.In addition, the C. albicans phosphatidylserine synthase mutant (cho1∆/∆) has no detectable phosphatidylserine and loss of phosphatidylserine causes alterations in the fungal cell wall. The cho1∆/∆ mutants’ cell wall defects include altered calcofluor white staining, resistance to the cell wall perturbing drug Caspofungin, and an altered physical appearance by transmission electron microscopy..We are using lipidomic analysis and transcriptomics of phosphatidylserine and phosphatidylethanolamine biosynthesis mutants to understand the role that phosphatidylserine and phosphatidylethanolamine play in controlling the cell wall in C. albicans.The elucidation of downstream effects of disruption of pathways involved in biosynthesis of phospholipids in C. albicans may validate these phospholipid biosynthesis enzymes as plausible anti-fungal drug targets. The role of phosphatidylserine and phosphatidylethanolamine in the maintenance of the fungal cell wall will also be of interest in determining how phospholipids impact signaling pathways and affect cell wall composition and architecture.

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