The primary aim of this project was to investigate whether the medically important fungal pathogen C. albicans, can be induced to undergo a programmed cell death response. Cell death in C. albicans was examined after treatment with low and high fungicidal doses of acetic acid, hydrogen peroxide and amphotericin B. Exposure of C. albicans cells to relatively low fungicidal doses of these agents produced cellular changes reminiscent of mammalian apoptosis; whilst, C. albicans cells treated at high fungicidal doses resulted in cellular changes typical of necrosis. The Ras/cAMP pathway in fungi is known to translate external signals to changes in gene expression and is involved in metabolism, proliferation and stress responses. In mammals, Ras has been demonstrated to exhibit both pro- and anti-apoptotic functions. Therefore, the role of the Ras/cAMP pathway in the programmed cell death events of C. albicans was investigated. The Ras/cAMP pathway was modulated in cells of C. albicans by genetic or pharmacological approaches. These cells were then exposed to a range of death-inducing treatments, and the temporal progression of cell death was studied. This detailed temporal analysis indicated that C. albicans Rasl is pro-apoptotic, and that the activation of the Ras/cAMP pathway accelerates the entry-rate of C. albicans cells into cell death responses. The exploitation of endogenous fungal programmed cell death responses, in terms of providing new anti-fungal agents, is a long way off. However, this research project was the first to demonstrate that a medically-important fungus can undergo programmed cell death events, and that these events can be triggered by treatment with exogenous drugs.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:590945 |
| Date | January 2004 |
| Creators | Phillips, Andrew John |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://digitool.abdn.ac.uk/R?func=search-advanced-go&find_code1=WSN&request1=AAIU186705 |
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