Kelly, Judy and Rowan, Raymond and McCann, Malachy and Kavanagh, Kevin
(2009)
Exposure to caspofungin activates Cap and Hog pathways
in Candida albicans.
Medical Mycology, 47.
pp. 697-706.
Abstract
Caspofungin is a member of the echinocandin group of antifungals and inhibits the
activity of B-glucan synthase thus disrupting cell wall formation and function. While
the potent antifungal activity of this agent is well established, this paper analyzed the
response of Candida albicans to caspofungin. Exposure of yeast cells to 0.19 μg/ml
caspofungin for 1 to 4 h induced nuclear translocation of Cap1p which was confirmed
by Western blotting and confocal microscopy. Caspofungin-treated cells demonstrated
increased expression of a number of genes associated with the oxidative stress response,
including glutathione reductase (GLR1), mitochondrial processing protease (MAS1)
and manganese-superoxide dismutase (SOD2) as well as elevated activity of glutathione
reductase and superoxide dismutase. Caspofungin treatment also leads to the nuclear
localization of Hog1p as visualized by Western blot using anti-phospho-p38 MAPK
(Thr180/Tyr182) antibody. This translocation event lead to increased mRNA levels of
catalase (CAT1) but not alkyl hydroperoxide reductase (AHP1). The activity of catalase
was increased and reached a maximum at 2 h. In addition, pre-exposure of C. albicans
to hydrogen peroxide (0.5 mM, 60 min) conferred an increased tolerance to caspofungin.
The data presented here highlight the potent antifungal activity of caspofungin and demonstrate
that upon exposure to this agent, C. albicans activates the Cap and Hog pathways
in an attempt to limit the oxidative and osmotic stresses associated with this drug.
| Item Type: |
Article
|
| Keywords: |
antifungal; Candida; caspofungin; oxidative stress in yeast; HOG1; Cap1p; |
| Academic Unit: |
Faculty of Science and Engineering > Chemistry |
| Item ID: |
9679 |
| Depositing User: |
Dr. Malachy McCann
|
| Date Deposited: |
13 Jul 2018 13:24 |
| Journal or Publication Title: |
Medical Mycology |
| Publisher: |
Taylor and Francis Online |
| Refereed: |
Yes |
| 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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