An Analysis of the Response of Aspergillus fumigatus and Candida albicans to Caspofungin

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.

Name dc:type.qualificationname

phd

Level dc:type.qualificationlevel

doctoral

Grantor dc:publisher.institution

National University of Ireland Maynooth

Year dc:date.issued

2014

Author dc:creator

• Eshwika, Ahmed

• Biology

Language dc:language

en