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Series GSE26925 Query DataSets for GSE26925
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
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)
GSM662985 DMSO Control, biological rep1
GSM662986 DMSO Control, biological rep2
GSM662987 DMSO Control, biological rep3
BioProject PRJNA136071

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Supplementary file Size Download File type/resource
GSE26925_RAW.tar 6.3 Mb (http)(custom) TAR (of CEL, CHP)
Raw data provided as supplementary file
Processed data included within Sample table
Processed data provided as supplementary file

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