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Fungicidal activity of thymol and carvacrol by disrupting ergosterol biosynthesis and membrane integrity against Candida

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Abstract

Natural isopropyl cresols have been reported to have antifungal activity. This work is an attempt to examine thymol and carvacrol against 111 fluconazole-sensitive and -resistant Candida isolates. Insight into the mechanism of action was elucidated by flow cytometric analysis, confocal imaging and ergosterol biosynthesis studies. The susceptibility tests for the test compounds were carried out in terms of minimum inhibitory concentrations (MICs), disc diffusion assays and time–kill curves against all Candida isolates by employing standard protocols. Propidium iodide (PI) cell sorting has been investigated by flow cytometric analysis and confocal imaging. Haemolytic activity on human erythrocytes was studied to exclude the possibility of further associated cytotoxicity. Both compounds were found to be effective to varying extents against all isolates, including the resistant strains. In contrast to the fungistatic nature of fluconazole, our compounds were found to exhibit fungicidal nature. Significant impairment of ergosterol biosynthesis was pronouncedly induced by the test entities. Negligible cytoxicity was observed for the same compounds. Furthermore, it was observed that the positional difference of the hydroxyl group in carvacrol slightly changes its antifungal activity. Carvacrol and thymol show strong fungicidal effect against all of the Candida isolates. The mechanisms of action of these natural isopropyl cresols appear to originate from the inhibition of ergosterol biosynthesis and the disruption of membrane integrity.

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Acknowledgements

The authors wish to thank Dr. Malini R. Capoor, Associate Professor, Department of Microbiology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India, for providing some of the clinical isolates of Candida. The authors also wish to thank Ms. Charu Tanwar, Sr. Tech. Assistant AIF, Jawaharlal Nehru University, for her kind assistance. This work was supported by the Indian Council of Medical Research (ICMR), New Delhi (Grant No. 59/24/2008/BMS/TRM [2008-04780]) to Dr. N. Manzoor, Dr. L. A. Khan and I. Xess.

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Authors and Affiliations

  1. Department of Biosciences, Jamia Millia Islamia, New Delhi, 110025, India

    A. Ahmad, A. Khan, S. Yousuf, L. A. Khan & N. Manzoor

  2. School of Biotechnology, Jawaharlal Nehru University, New Delhi, 110067, India

    F. Akhtar

  3. Department of Microbiology, All India Institute of Medical Sciences, New Delhi, 110029, India

    I. Xess

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  1. A. Ahmad
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  2. A. Khan
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  3. F. Akhtar
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  4. S. Yousuf
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  5. I. Xess
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  6. L. A. Khan
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  7. N. Manzoor
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Corresponding author

Correspondence to N. Manzoor.

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A. Ahmad and A. Khan contributed equally to the study.

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Ahmad, A., Khan, A., Akhtar, F. et al. Fungicidal activity of thymol and carvacrol by disrupting ergosterol biosynthesis and membrane integrity against Candida . Eur J Clin Microbiol Infect Dis 30, 41–50 (2011). https://doi.org/10.1007/s10096-010-1050-8

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  • DOI: https://doi.org/10.1007/s10096-010-1050-8

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