 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Jan 28, 2011 |
| Title |
Gene expression response to the antifungal compound plakortide F acid in S. cerevisiae |
| Platform organisms |
Schizosaccharomyces pombe; Saccharomyces cerevisiae |
| Sample organism |
Saccharomyces cerevisiae S288C |
| Experiment type |
Expression profiling by array
|
| Summary |
Plakortide F acid (PFA), a marine-derived polyketide endoperoxide, exhibits strong inhibitory activity against the opportunistic fungal pathogens Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus. In the present study, transcriptional profiling coupled with mutant and biochemical analyses were conducted using the model organism Saccharomyces cerevisiae, to investigate the mechanism of action of this compound. PFA elicited a transcriptome response indicative of a Ca2+ imbalance, affecting the expression of genes known to be responsive to altered cellular calcium levels. Several additional lines of evidence obtained supported a role for Ca2+ in PFA's activity. First, mutants lacking calcineurin and various Ca2+ transporters including pumps (Pmr1 and Pmc1) and channels (Cch1 and Mid1) showed increased sensitivity to PFA. In addition, the calcineurin inhibitors FK506 and cyclosporine A strongly enhanced PFA activity in wild-type cells. Furthermore, PFA activated the transcription of a lacZ reporter driven by the calcineurin-dependent response element. Finally, elemental analysis indicated a significant increase in intracellular calcium levels in PFA-treated cells. Collectively, our results demonstrate that PFA mediates its antifungal activity by perturbing Ca2+ homeostasis, thus representing a potentially novel mechanism distinct from that of currently used antifungal agents.
DNA microarray analysis of gene expression response to the antifungal compound plakortide F acid in yeast
|
| |
|
| Overall design |
S. cerevisiae S288C cells at OD 0.2 were treated with either plakortide F acid (PFA) at IC50 concentration (0.62 ug/ml), or solvent (0.25% DMSO), allowed to grow to OD 0.5, then harvested and frozen. Three biological replicate samples were analyzed for each treatment.
|
| |
|
| Contributor(s) |
Agarwal AK |
| Citation(s) |
21300833 |
| |
| Submission date |
Jan 28, 2011 |
| Last update date |
Feb 21, 2017 |
| Contact name |
Ameeta Agarwal |
| E-mail(s) |
aagarwal@olemiss.edu
|
| Phone |
662-915-1218
|
| Organization name |
University of Mississippi
|
| Department |
National Center for Natural Products Research
|
| Street address |
NCNPR, Room 2049
|
| City |
University |
| State/province |
MS |
| ZIP/Postal code |
38677 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL2529 |
[Yeast_2] Affymetrix Yeast Genome 2.0 Array |
|
| Samples (6)
|
|
| Relations |
| BioProject |
PRJNA136071 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE26925_RAW.tar |
6.3 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
|
|
|
|
 |
Less...
More...