Date of Award

5-2023

Document Type

Thesis

Department

Biochemistry

Committee Chair/Advisor

Dr. Lukasz Kozubowski

Abstract

Cryptococcus neoformans is a pathogenic basidiomycetous yeast that causes meningitis in immunocompromised patients. This lethal fungus is sometimes referred to as the “sugar coated killer” due to its polysaccharide capsule. It is estimated that 152,000 cases of cryptococcal infection occur each year and result in 112,000 deaths. The ability of C. neoformans to adapt to host temperature is a main factor responsible for virulence. Septins are conserved filament-forming GTPases that are confirmed to be involved in cytokinesis and morphogenesis and have been implicated in heat stress response and virulence of C. neoformans. C. neoformans genome encodes four septins, Cdc3, Cdc10, Cdc11, and Cdc12 that form a complex at the mother-bud neck where they participate in cytokinesis through ill-defined mechanism. Our preliminary data indicate that the septin complex also forms at the plasma membrane (PM) specifically at 37℃, suggesting that septins contribute to stress response by interacting with PM and potentially supporting PM homeostasis. The C. neoformans septin interactome had not been previously thoroughly analyzed for potential interacting partners. In a preliminary experiment conducted by this research group, tandem-mass spectrometry was utilized to identify proteins associated with the septin complex. Based on these data, septins are hypothesized to be involved in cell wall integrity and plasma membrane homeostasis. Strains lacking septins were found hypersensitive to cell wall and PM disrupting agents, which further supports this hypothesis.

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