Saccharomyces cerevisiae
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PROVIDER: PRJNA108961 | ENA |
REPOSITORIES: ENA
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Project description:Gene expression response to the antifungal compound plakortide F acid in S. cerevisiae
| PRJNA136071 | ENA
Project description:A systematic approach allowing the identification of the molecular way-of-action of novel potential drugs represents the golden-tool for drug-discovery. While high-throughput screening technologies of large libraries is now well established, the assessment of the drug targets and mechanism of action is still under development. Taking advantage of the yeast model Saccharomyces cerevisiae, we herein applied BarSeq, a Next Generation Sequencing-based method to the analysis of both haploinsufficiency and homozygous fitness effects of a novel antifungal drug ('089') compared to the well-known antifungal ketoconazole. '089' was a novel compound identified in during a screen for antifungal drugs, as it was showing fungicidal effects, and able to affect the yeast fitness at the mitochondrial level (Stefanini et al., 2010. (Dissection of the Effects of Small Bicyclic Peptidomimetics on a Panel of Saccharomyces cerevisiae Mutants;.J Biol Chem, 285: 23477-23485.) Integrative bioinformatic analysis of BarSeq, whole genome expression analysis and classical biological assays identified the target and cell pathways affected by the novel antifungal. Confirmation of the effects observed in the yeast model and in pathogenic fungi further demonstrated the reliability of the multi-sided approach and the novelty of the targets and way-of-action of the new class of molecules studied representing a valuable source of novel antifungals.
2016-04-30 | E-SYBR-6 | biostudies-arrayexpress
Project description: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.
2012-02-08 | GSE35604 | GEO
Project description:Fungal group III histidine kinases are the molecular targets of some classes of fungicides. In contrast to the yeast Saccharomyces cerevisiae, the fungal pathogen Candida albicans possesses a group III histidine kinase, CaNik1p, also called Cos1p. To investigate the function of CaNIK1, the gene was expressed in S. cerevisiae. The transformants became susceptible to antifungal compounds to which the wild-type strain is resistant. The susceptibility was related to the activation of the MAP kinase Hog1p of the osmotic stress response pathway. Gene expression analysis revealed a strong overlap of the responses to osmotic stress and to fludioxonil at early time points. While the response to fludioxonil persisted, the response to osmotic stress was diminished with time.
2014-02-01 | GSE25002 | GEO
Project description:Gene expression response to the antifungal compound sampangine
| PRJNA108251 | ENA
Project description: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
2011-01-28 | GSE26925 | GEO
Project description:Transcriptomic study to characterize the interaction of the Penicillium expansum antifungal protein PeAfpA with the the model yeast Saccharomyces cerevisiae. For this, the transcriptome of S. cerevisiae BY4741 strain was compared among samples treated with increasing concentrations of PeAfpA.
2023-11-09 | GSE233704 | GEO
Project description: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 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.
2011-01-28 | E-GEOD-26925 | biostudies-arrayexpress
Project description: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 ?-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. 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.
2012-02-08 | E-GEOD-35604 | biostudies-arrayexpress
Project description:Fungal group III histidine kinases are the molecular targets of some classes of fungicides. In contrast to the yeast Saccharomyces cerevisiae, the fungal pathogen Candida albicans possesses a group III histidine kinase, CaNik1p, also called Cos1p. To investigate the function of CaNIK1, the gene was expressed in S. cerevisiae. The transformants became susceptible to antifungal compounds to which the wild-type strain is resistant. The susceptibility was related to the activation of the MAP kinase Hog1p of the osmotic stress response pathway. Gene expression analysis revealed a strong overlap of the responses to osmotic stress and to fludioxonil at early time points. While the response to fludioxonil persisted, the response to osmotic stress was diminished with time. S. cerevisiae expressing Candida albicans Nik1p were treated with 10 µg/ml fludioxonil. As a comparison, another culture of S. cerevisiae expressing Candida albicans Nik1p was treated with 1 M sorbitol to induce osmotic stress response. One culture remained untreated as a control. From all cultures, samples were taken after a duration of 15, 30 and 60 min.
2014-02-01 | E-GEOD-25002 | biostudies-arrayexpress