Saccharomyces cerevisiae
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ABSTRACT:
PROVIDER: PRJNA113385 | ENA |
REPOSITORIES: ENA
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Project description:Antagonism between two mechanisms of antifungal drug resistance
| PRJNA94857 | 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:Growth assay in the presence of a toxic chemical (sr7575) that uses the barcoded collections of yeast gene deletions (haploid, diploid, DamP) to identify deletion strains that are hypersensitive to the drug. Two-condition experiment â growth of a pool of strains in the presence or absence of the drug. Two independent biological replicates for each collection (haploids - homozygous and diploids â heterozigous). Data for the article: Shriya Raj, Karthik Krishnan, David S Askew, Olivier Helynck, Peggy Suzanne, Aureslien Lesnard, Sylvain Rault, Ute Zeidler, Christophe d'Enfert, Jean-Paul Latgé, Hélène Munier-Lehmann and Cosmin Saveanu. Toxicity of a novel antifungal compound is modulated by ERAD components. Antimicrobial Agents and Chemotherapy.
2015-12-09 | E-GEOD-60934 | biostudies-arrayexpress
Project description:We examined the gene expression changes resulting from the evolution of resistance in experimental populations of the yeast Saccharomyces cerevisiae subjected to two antifungal drugs, fluconazole (FLC) and amphotericin B (AmB). Fluconazole resistance may involve increased efflux or changes in sterol metabolism, while AmB resistance generally involves changes in sterol metabolism; for all of these types of resistance, the gene expression changes are extensive. The goal of these experiments was to test whether failure of gene expression changes all downstream of the original mutation for drug resistance would affect the ability of a mutant cell to evolve and/or to support a drug-resistant phenotype.
2008-07-28 | GSE12055 | GEO
Project description:Aneuploidy and the evolution of aneuploid karyotypes of Candida albicans strains was identified using aCGH. Whole chromosome and segmental aneuploidies, (specifically on the left arm of chromosome 5 - shown to be due to isochromosome formation) are associated with the appearance of resistance to the antifungal drug fluconazole. Keywords: Comparative Genomic Hybridization
2006-06-30 | GSE4995 | GEO
Project description:Gene expression response to the antifungal compound sampangine in S. cerevisiae
| PRJNA108961 | ENA
Project description:Functional Variomics Library testing for drug resistance in yeast
| PRJNA124523 | ENA
Project description:Aneuploidy and the evolution of aneuploid karyotypes of Candida albicans strains was identified using aCGH. Whole chromosome and segmental aneuploidies, (specifically on the left arm of chromosome 5 - shown to be due to isochromosome formation) are associated with the appearance of resistance to the antifungal drug fluconazole. Keywords: Comparative Genomic Hybridization Hybridization of all strains was compared to the hybridization of SC5314, the sequenced laboratory strain.
2006-06-30 | E-GEOD-4995 | biostudies-arrayexpress
Project description:Invasive fungal infections (IFIs) are difficult to treat. Few effective antifungal drugs are available and many have problems with toxicity, efficacy and drug-resistance. To overcome these challenges, existing therapies may be enhanced using more than one agent acting in synergy. Previously, we have found amphotericin B (AMB) and the iron chelator, lactoferrin (LF), were synergistic against Cryptococcus neoformans and Saccharomyces cerevisiae. This study investigates the mechanism of AMB+LF synergy, using RNA-seq and network analyses. Genes involved in iron homeostasis showed increased expression upon treatment with AMB alone. Unexpectedly, AMB+LF treatment did not lead to increased expression of iron or zinc homeostasis genes however we observed decreased expression of oxidative stress response genes. Addition of iron or zinc to AMB+LF treated cells did not rescue the synergy, supporting the likelihood that the mechanism of synergy involves more than iron and zinc chelation. We clustered genes based on patterns of co-expression and found by network analysis that many genes involved in iron and zinc homeostasis, which have dysregulated expression upon AMB+LF treatment, are targets of transcription factors Aft1p and Zap1p. Hypothesizing that these might play a key role in the synergistic response, knock-out mutants of Aft1 and Zap1 were tested for increased sensitivity to AMB and oxidative stress. Both mutants showed hypersensitivity towards these treatments. Our results suggest the mechanism of AMB+LF synergy involves disruption to oxidative stress response, in addition to chelation of iron and zinc. Since Zap1 is conserved in C. neoformans and contains a putative drug binding domain, we suggest novel Zap1 binding molecules could be combined with existing antifungals to serve as synergistic antifungal treatments for this species.
2016-12-04 | GSE80357 | GEO
Project description:The polyploid S. cerevisiae karyotypes were analyzed by array-CGH to identify the deletion or duplication of gene or chromosome during the strain construction and after experimental evolution.
2016-10-11 | GSE76595 | GEO