Expression analysis of novel and known antifungal drugs using S. cerevisiae as a model

A systematic approach allowing the identification of the molecular way of action of novel potential drugs still represents the golden-tool for drug-discovery researchers. 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 compared to the well-known antifungal, ketoconazole. 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 as well as in pathogenic fungi further demonstrated the reliability of the multi-sided approach and the novelty of the targets and mode of action of the new class of molecules studied that thus represent a valuable source of novel antifungals. Two-condition experiments, drug vs. DMSO-treated S. cerevisiae cells. Analyzed drugs: two concentrations of ketoconazole (2.5 uM and 50 uM) and one concentration of the novel proposed antifungal 089. Biological replicates: 3 control replicates for each experiment.