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Download StatisticsZhou, Xin (2022). The mechanisms driving titanization of Cryptococcus neoformans and their impact on host-interaction. University of Birmingham. Ph.D.
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Zhou2022PhD.pdf
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Abstract
Cryptococcus neoformans, as a major human fungal pathogen, can cause infection at both lungs and brains of immunocompromised and immunocompetent individuals. During the infection process, a highly heterogeneous population emerges in response to the host environment, and within this population, large yeast (titan) cells are required for survival and proliferation. However, the detailed characterization of different titan sub-populations, as well as their roles in regulating the infection process, has not been fully explored. This thesis (chapter 2) starts with characterizing titan population heterogeneity of typical laboratory strain H99 together with three other clinical strains. This chapter aims to help us to understand the relationship between different titan sub-populations and the changes cells undergo after being exposed to titan induction, in strains with different capabilities to titanize. After that, chapter 3 shows how oxidative and nitrosative stress imposed by host immune response can affect titan cell formation. In this chapter, the fungal endogenous superoxide production is also found to be required for yeast-to-titan transition, which can further lead to DNA damage accumulation in titanized cells. Finally, in chapter 4, we reveal that there is a positive correlation between superoxide production, DNA damage, and titan cell formation. One possible mechanism underlying this correlation is that the cell cycle is arrested by accumulation of DNA damage, as a result of sustained superoxide activity and delayed DNA repair. In summary, this thesis reveals novel insights on how small cells from titan population impact host interaction, how the host immune response can contribute to titan cell formation by affecting the endogenous stress response, and the regulatory mechanism of this stress response.
| Type of Work: | Thesis (Doctorates > Ph.D.) | |||||||||
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| Award Type: | Doctorates > Ph.D. | |||||||||
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| Licence: | All rights reserved | |||||||||
| College/Faculty: | Colleges (2008 onwards) > College of Life & Environmental Sciences | |||||||||
| School or Department: | School of Biosciences | |||||||||
| Funders: | Other | |||||||||
| Other Funders: | Darwin Trust | |||||||||
| Subjects: | Q Science > QR Microbiology | |||||||||
| URI: | http://etheses.bham.ac.uk/id/eprint/12203 |
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