The antifungal mode of action of thymol was investigated by a chemical-genetic profile analysis. Growth of each of ̃ 4700 haploid Saccharomyces cerevisiae gene deletion mutants was monitored on medium with a subinhibitory concentration (50 μg/ml) of thymol and compared to growth on non-thymol control medium. This analysis revealed that, of the 76 deletion mutants with the greatest degree of susceptibility to thymol, 29% had deletions in genes involved in telomere length maintenance. A telomere restriction fragment (TRF) length assay showed that yeast exposed to a subinhibitory concentration of thymol for 15 days had telomere size reductions of 13-20% compared to non-thymol controls. By accelerating telomere shortening, thymol may increase the rate of cell senescence and apoptosis. Furthermore, real-time RT-PCR analysis revealed approximately two-fold reductions in EST2 mRNA but no change in TLC1 RNA in thymol-treated S. cerevisiae relative to untreated cells. EST2 encodes the essential reverse transcriptase subunit of telomerase that uses TLC1 RNA as a template during addition of TG(1-3) repeats to maintain telomere ends. This study provides compelling evidence that a primary mode of thymol antifungal activity is through inhibition of transcription of EST2 and thus telomerase activity.

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Keywords β-galactosidase expression assay, Antifungal molecular mechanism, Chemical-genetic profile analysis, Reverse transcriptase subunit of telomerase, Telomere length maintenance, Thymol antifungal mode of action
Persistent URL dx.doi.org/10.3109/13693786.2013.795664
Journal Medical Mycology
Citation
Darvishi, E. (Emad), Omidi, M. (Mansoor), Bushehri, A.A. (Ali Akbar), Golshani, A, & Smith, M. (2013). Thymol antifungal mode of action involves telomerase inhibition. Medical Mycology, 51(8), 826–834. doi:10.3109/13693786.2013.795664