Evans, Robert J. (2016). The role of cryptococcus neoformans derived phospholipase B1 during host infection. University of Birmingham. Ph.D.
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Evans16PhD.pdf
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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: | Thesis (Doctorates > Ph.D.) | ||||||
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Award Type: | Doctorates > Ph.D. | ||||||
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College/Faculty: | Colleges (2008 onwards) > College of Life & Environmental Sciences | ||||||
School or Department: | School of Biosciences | ||||||
Funders: | None/not applicable | ||||||
Subjects: | Q Science > QR Microbiology | ||||||
URI: | http://etheses.bham.ac.uk/id/eprint/6634 |
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