Chemical-Genetic profile Analysis of Thymol in Saccharomyces cerevisiae

The antifungal activity of thymol was evaluated using the broth microdilution assay with Saccharomyces cerevisiae. The results indicate that minimum inhibitory concentration (MIC100) for thymol is in the range of 80-100 µg/ml. Chemical-genetic profile analysis was completed with thymol using ~4700 haploid S. cerevisiae gene deletion mutants to find out the mode of action of thymol in the yeast cell. 89 S. cerevisiae deletion mutants with the greatest degree of susceptibility to subinhibitory concentration of thymol (50 µg/ml) were selected by digital analysis. Cellular roles of deleted genes in the most susceptible mutants and gene ontology annotation analysis using online gene profiling software (Profcom, gprofiler and GeneMANIA) indicate that the targets for thymol include pathways involved in telomere length maintenance. Spot test analysis of targeted mutants performed to confirm the accuracy of our large-scale approach to detect drug sensitive mutants. Inhibitory effects of thymol on the genes that are involved in telomere length maintenance probably cause telomere shortening during the cell cycle, apoptosis induction and cell growth inhibition in the yeast cell.