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The role of cryptococcus neoformans derived phospholipase B1 during host infection

Evans, Robert J. (2016)
Ph.D. thesis, University of Birmingham.

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Abstract

Cryptococcus neoformans is an opportunistic fungal pathogen and a leading cause of fungal infection related fatalities in immunocompromised hosts. Compared to well-studied; Cryptococcus neoformans virulence factors like the polysaccharide capsule and melanin synthesis, very little is known about phospholipase B1 (Plb1). Plb1 is a phospholipid modifying enzyme that is implicated in multiple stages of cryptococcal pathogenesis. Herein I demonstrate that a Plb 1 deficient strain of C.neoformans has a profound defect in intracellular growth within macrophages. In addition, I show that the Δplb1 strain undergoes a novel morphological change during in vitro and in vivo infection, resulting in a sub-population of very large 'titan cells' that may arise as a result of the mutant's inability to cope within the macrophage. I go on to test whether these phenotypes are due to a reduction in eicosanoid production caused by Plb 1 deficiency. Finally, I present an addition project where I optimise a C. neoforman's intracellular proliferation assay for high throughput analysis via flow cytometry.
This work provides a new insight into the function of this unappreciated virulence factor and helps to lay the foundation for new treatment strategies to combat cryptococcosis.

Type of Work:Ph.D. thesis.
Supervisor(s):May, Robin C.
School/Faculty:Colleges (2008 onwards) > College of Life & Environmental Sciences
Department:School of Biosciences
Subjects:QR Microbiology
Institution:University of Birmingham
ID Code:6634
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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