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Macrophage – cryptococcus interactions during cryptococcosis

Voelz, Kerstin (2010)
Ph.D. thesis, University of Birmingham.

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Abstract

The human fungal pathogens Cryptococcus neoformans and C. gattii cause life-threatening infections of the central nervous system. One of the major characteristics of cryptococcal disease is the ability of the pathogen to parasitise upon phagocytic effector cells. Cryptococcus can survive and proliferate within macrophages, and is also capable of escaping into the intracellular environment via a non-lytic mechanism (‘expulsion’) and can be transferred directly from one cell to another (lateral transfer). In the first part of this thesis, I demonstrate that enhanced Th2, but not Th1, cytokine levels lead to increased intracellular cryptococcal proliferation but lower levels of cryptococcal expulsion. In the second part, I describe the generation and characterisation of GFP-expressing derivates of two widely used cryptococcal strains: C. neoformans serotype A type strain H99 and C. gattii serotype B type strain R265. Furthermore, I have developed a method to effectively and rapidly investigate macrophage parasitism by flow cytometry that preserves the accuracy of current approaches but offers a four-fold improvement in speed. The final part dissects the regulation and induction of mitochondrial tubularisation in hypervirulent C. gattii strains and describes the first steps towards a comparative mitochondrial genome sequencing approach to identify the underlying molecular mechanisms.

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:QH301 Biology
QM Human anatomy
Institution:University of Birmingham
ID Code:1194
This unpublished thesis/dissertation is copyright of the author and/or third parties.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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