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| Status |
Public on Feb 08, 2012 |
| Title |
Gene expression response to the antifungal compound 6-Nonadecynoic acid (6-NDA) in Saccharomyces cerevisiae and Candida albicans |
| Platform organisms |
Schizosaccharomyces pombe; Saccharomyces cerevisiae; Candida albicans |
| Sample organisms |
Saccharomyces cerevisiae; Candida albicans |
| Experiment type |
Expression profiling by array
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| Summary |
6-Nonadecynoic acid (6-NDA), a plant-derived acetylenic acid, exhibits strong inhibitory activity against the human fungal pathogens Candida albicans, Aspergillus fumigatus, and Trichophyton mentagrophytes. 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. 6-NDA elicited a transcriptome response indicative of fatty acid stress, altering the expression of genes known to be affected when yeast cells are grown in the presence of oleate. Mutants of S. cerevisiae lacking transcription factors that regulate fatty acid beta-oxidation showed increased sensitivity to 6-NDA. Fatty acid profile analysis indicated that 6-NDA inhibited the formation of fatty acids longer than 14 carbons in length. In addition, the growth inhibitory effect of 6-NDA was rescued in the presence of exogenously supplied oleate. To investigate the response of a pathogenic fungal species to 6-NDA, transcriptional profiling and biochemical analyses were also conducted in C. albicans. The transcriptional response and fatty acid profile of C. albicans were comparable to those obtained in S. cerevisiae, and the rescue of growth inhibition with exogenous oleate was also observed in C. albicans. In addition, 6-NDA enhanced the potency of the antifungal drug fluconazole in a fluconazole-resistant clinical isolate of C. albicans. Collectively, our results indicate that the antifungal activity of 6-NDA is mediated by a disruption in fatty acid homeostasis, and that this compound has potential utility in combination therapy in the treatment of drug-resistant fungal infections.
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| Overall design |
Cultures of S. cerevisiae strain S288C were started at OD600 of 0.1, allowed to grow to OD600 of 0.2, then treated with either DMSO (0.25%) or 6-NDA at the IC50 concentration (2.2 ug/ml). When OD600 of 0.5 was reached, cells were harvested and frozen. Two biological replicate cultures were grown for each treatment, and RNA from each replicate was hybridized to 2 independent arrays, resulting in 4 hybridizations for each treatment.
Cultures of C. albicans strain SC5314 were started at OD600 of 0.1, allowed to grow to OD600 of 0.2, then treated with either DMSO (0.25%) or 6-NDA at the IC50 concentration (4 ug/ml). When OD600 of 0.5 was reached, cells were harvested and frozen. Three biological replicate cultures were grown for each treatment, and RNA from each replicate was hybridized as dye-swap pairs, resulting in 6 hybridizations for each treatment.
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| Contributor(s) |
Agarwal AK |
| Citation(s) |
22430960 |
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| Submission date |
Feb 07, 2012 |
| Last update date |
Feb 21, 2017 |
| Contact name |
Ameeta Agarwal |
| E-mail(s) |
aagarwal@olemiss.edu
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| Phone |
662-915-1218
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| Organization name |
University of Mississippi
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| Department |
National Center for Natural Products Research
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| Street address |
NCNPR, Room 2049
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| City |
University |
| State/province |
MS |
| ZIP/Postal code |
38677 |
| Country |
USA |
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| Platforms (2) |
| GPL2529 |
[Yeast_2] Affymetrix Yeast Genome 2.0 Array |
| GPL15195 |
University of Texas UTHSC-H Candida albicans v2.0 |
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| Samples (14)
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| GSM871550 |
6-NDA-treated, biological repA2 |
| GSM871551 |
DMSO Control, biological repB1 |
| GSM871552 |
DMSO Control, biological repB2 |
| GSM871553 |
6-NDA-treated, biological repB1 |
| GSM871554 |
6-NDA-treated, biological repB2 |
| GSM871555 |
DMSO-treated (Cy5) vs. 6-NDA-treated (Cy3) Replicate 1 |
| GSM871556 |
DMSO-treated (Cy3) vs. 6-NDA-treated (Cy5) Replicate 1 |
| GSM871557 |
DMSO-treated (Cy5) vs. 6-NDA-treated (Cy3) Replicate 2 |
| GSM871558 |
DMSO-treated (Cy3) vs. 6-NDA-treated (Cy5) Replicate 2 |
| GSM871559 |
DMSO-treated (Cy5) vs. 6-NDA-treated (Cy3) Replicate 3 |
| GSM871560 |
DMSO-treated (Cy3) vs. 6-NDA-treated (Cy5) Replicate 3 |
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| Relations |
| BioProject |
PRJNA152529 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE35604_RAW.tar |
9.7 Mb |
(http)(custom) |
TAR (of CEL, CHP, TXT) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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