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α-Bisabolol inhibits Aspergillus fumigatus Af239 growth via affecting microsomal ∆24-sterol methyltransferase as a crucial enzyme in ergosterol biosynthesis pathway

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Abstract

Finding new compounds with antifungal properties is an important task due to the side effects of common antifungal drugs and emerging antifungal resistance in fungal strains. ∆24-sterol methyltransferase (24-SMT) is a crucial enzyme that plays important roles in fungal ergosterol biosynthesis pathway and is not found in humans. In the present study, the effects of α-bisabolol on Aspergillus fumigatus Af239 growth and ergosterol synthesis on the base of 24-SMT enzyme activity were studied; in addition, the expression of erg6, the gene encoded 24-SMT, was considered. To our knowledge, this is the first report demonstrating that α-bisabolol inhibits A. fumigatus growth specifically via suppressing fungal 24-SMT. Since this enzyme is a specific fungal enzyme not reported to exist in mammalian cells, α-bisabolol may serve as a lead compound in the development of new antifungal drugs. Fungi were cultured in presence of serial concentrations of α-bisabolol (0.281–9 mM) for 3 days at 35 °C. Mycelia dry weight was determined as an index of fungal growth and ergosterol content was assessed. Microsomal 24-SMT activity was assayed in presence of α-bisabolol as an inhibitor, lanosterol as a substrate and [methyl-H3] AdoMet (S-Adenosyl methionin). In addition, the expression of erg 6 gene (24-SMT encoding gene) was determined after treatments with various concentrations of α-bisabolol. Our results demonstrated that α-bisabolol strongly inhibited A. fumigatus growth (35.53–77.17%) and ergosterol synthesis (26.31–73.77%) dose-dependently and suppressed the expression of erg 6 gene by 76.14% at the highest concentration of 9 mM. α-bisabolol inhibited the activity of 24-SMT by 99% at the concentration of 5 mM. Taken together, these results provides an evidence for the first time that α-bisabolol inhibits A. fumigatus Af239 growth via affecting microsomal ∆24-sterol methyltransferase as a crucial enzyme in ergosterol biosynthetic pathway.

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Acknowledgements

This work was financially supported by the Pasteur Institute of Iran (Project No. 647).

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Authors and Affiliations

  1. Department of Mycology, Pasteur Institute of Iran, 13164, Tehran, Iran

    Zahra Jahanshiri, Farnoush Asghari-Paskiabi & Mehdi Razzaghi-Abyaneh

  2. Department of Mycology, Faculty of Medical Sciences, Tarbiat Modares University, 14115-331, Tehran, Iran

    Masoomeh Shams-Ghahfarokhi

  3. Department of Biochemistry, Pasteur Institute of Iran, 13164, Tehran, Iran

    Reza Saghiri

Authors
  1. Zahra Jahanshiri
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  2. Masoomeh Shams-Ghahfarokhi
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  3. Farnoush Asghari-Paskiabi
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  5. Mehdi Razzaghi-Abyaneh
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Correspondence to Mehdi Razzaghi-Abyaneh.

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Jahanshiri, Z., Shams-Ghahfarokhi, M., Asghari-Paskiabi, F. et al. α-Bisabolol inhibits Aspergillus fumigatus Af239 growth via affecting microsomal ∆24-sterol methyltransferase as a crucial enzyme in ergosterol biosynthesis pathway. World J Microbiol Biotechnol 33, 55 (2017). https://doi.org/10.1007/s11274-017-2214-9

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