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Title: Dynamic responses of the fungal cell wall to stress and antifungal treatment
Author: Walker, Louise
ISNI:       0000 0004 2690 9909
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2010
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The main aim of this project was to determine the potential of increased chitin content as a mechanism of resistance to caspofungin in different fungal pathogens. C. albicans wild-type cells were pre-grown with a combination of CaCl2 and CFW prior to caspofungin treatment. This result sin a three-fold increase in cell wall chitin. Wild-type cells, which had elevated chitin content, were less susceptible to caspofungin. Priming cells to activated chitin synthesis was also able to compensate for the loss of the normally essential CaCHS1, through formation of three novel forms of salvage septa. In the absence of both CaChs1 and CaChs3, which are typically involved in septum formation, the class I chitin synthases, CaChs2 and CaChs8, could be stimulated to synthesise a proximally offset salvage septum. When CaChs3 was the only remaining chitin synthase, treatment with CaCl2 and CFW, led to the formation of thick chitin-rich salvage septa. CaChs2 and CaChs3 could be stimulated by treatment with CaCl2 and CFW to synthesise a thin salvage septum similar to the septum of wild-type cells. All three salvage septa were capable of restoring viability and cell division in C. albicans. The compensatory increase in chitin content in response to caspofungin treatment was not specific to C. albicans because clinical isolates of C. tropicalis, C. parapsilosis and C. guilliermondii and the filamentous fungus, A. fumigatus, also demonstrated an increase in chitin content after treatment with caspofungin. Isolates of C. glabrata and C. krusei showed no change in chitin content when exposed to caspofungin. The results of this thesis highlight the potential for using chitin synthase inhibitors in combination therapy with the echinocandins.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Chitin ; Candida Albicans