Eshwika, Ahmed
(2014)
An Analysis of the Response of Aspergillus fumigatus
and Candida albicans to Caspofungin.
PhD thesis, National University of Ireland Maynooth.
Abstract
The filamentous fungus Aspergillus fumigatus is capable of causing a range of
diseases in immunocompromised patients and is responsible for up to 3% of all hospitalbased
deaths in the EU. The yeast Candida albicans induces a range of diseases in
immunocompromised patients. Caspofungin is a recently introduced antifungal
compound that has good efficacy against these fungi with minimal side effects. The aim
of the work presented here was to characterise the response of A. fumigatus and C.
albicans to caspofungin. The results obtained demonstrated that caspofungin has potent
anti-fungal activity and retards fungal growth but that the response of fungi to this drug
is influenced by a variety of environmental factors (e.g. pH, serum, glucose). Exposure
of A. fumigatus hyphae to this drug leads to the release of amino acids and gliotoxin.
There is also an increase in internal levels of gliotoxin following exposure to the drug.
Prolonged exposure to caspofungin leads to reduced growth but greatly elevated levels
of secreted and internal gliotoxin. Since this toxin is highly immunosuppressive it is
possible that in vivo elevated levels of this toxin may exacerbate the deterioration in the
patient’s condition following caspofungin therapy. A. fumigatus hyphae exposed to
caspofungin demonstrated an increase in the expression of proteins associated with an
oxidative response (e.g. catalase, antibiotic response protein) and in the activity of
selected enzymes (catalase, glutathione reductase and superoxide dismutase). The
results presented in this thesis demonstrate that caspofungin is a potent antifungal agent
but that A. fumigatus responds to the drug by increasing the synthesis of gliotoxin and
by inducing an oxidative stress response.
| Item Type: |
Thesis
(PhD)
|
| Keywords: |
Aspergillus fumigatus; Candida albicans; Caspofungin; |
| Academic Unit: |
Faculty of Science and Engineering > Biology |
| Item ID: |
5804 |
| Depositing User: |
IR eTheses
|
| Date Deposited: |
10 Feb 2015 11:58 |
| URI: |
|
| Use Licence: |
This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available
here |
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