The role of cryptococcus neoformans derived phospholipase B1 during host infection

Evans, Robert J. (2016). The role of cryptococcus neoformans derived phospholipase B1 during host infection. University of Birmingham. Ph.D.

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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.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):