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Saccharomyces cerevisiae

ABSTRACT: Experimental assay of a fitness landscape on a macroevolutionary scale

PROVIDER: PRJNA390287 | ENA |

REPOSITORIES: ENA

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Dataset's files

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			Action	DRS
	SRR5680230_1.fastq.gz	Fastqsanger.gz
	SRR5680230_2.fastq.gz	Fastqsanger.gz
	SRR5680240_1.fastq.gz	Fastqsanger.gz
	SRR5680240_2.fastq.gz	Fastqsanger.gz
	SRR5680250_1.fastq.gz	Fastqsanger.gz

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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.

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