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Insights into the mode of action of anticandidal herbal monoterpenoid geraniol reveal disruption of multiple MDR mechanisms and virulence attributes in Candida albicans

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Abstract

The anticandidal potential of Geraniol (Ger) against Candida albicans has already been established. The present study reveals deeper insights into the mechanisms of action of Ger. We observed that the repertoire of antifungal activity was not only limited to C. albicans and its clinical isolates but also against non-albicans species of Candida. The membrane tampering effect was visualized through transmission electron micrographs, depleted ergosterol levels and altered plasma membrane ATPase activity. Ger also affects cell wall as revealed by spot assays with cell wall-perturbing agents and scanning electron micrographs. Functional calcineurin pathway seems to be indispensable for the antifungal effect of Ger as calcineurin signaling mutant was hypersensitive to Ger while calcineurin overexpressing strain remained resistant. Ger also causes mitochondrial dysfunction, impaired iron homeostasis and genotoxicity. Furthermore, Ger inhibits both virulence attributes of hyphal morphogenesis and biofilm formation. Taken together, our results suggest that Ger is potential antifungal agent that warrants further investigation in clinical applications so that it could be competently employed in therapeutic strategies to treat Candida infections.

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Acknowledgments

S.H. thank for the financial assistance in the form of Young Scientist award (SR/FT/LS-12/2012) from Science and Engineering Research Board (SERB), New Delhi. We are grateful to Joseph Heitman for providing Candida reference and calcineurin mutant strains as generous gift. We are grateful to Sumathi Muralidhar, Regional Sexually Transmitted Disease Research Centre, Safdarjung Hospital, New Delhi, for providing clinical isolates of C. albicans and non-C. albicans strains. We acknowledge the assistance of Jasvir Singh and Rita Salam, IARI, New Delhi, for assisting us in TEM and SEM experiments, respectively. We thank Rajendra Prasad, Director of Amity Institute of Biotechnology for encouragement and providing the available facilities for research in the institute.

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    1. Amity Institute of Biotechnology, Amity University Haryana, Manesar, Gurgaon, 122413, India

      Shweta Singh, Zeeshan Fatima & Saif Hameed

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    1. Shweta Singh
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    Communicated by Erko Stackebrandt.

    Shweta Singh and Zeeshan Fatima have contributed equally to this work.

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    Singh, S., Fatima, Z. & Hameed, S. Insights into the mode of action of anticandidal herbal monoterpenoid geraniol reveal disruption of multiple MDR mechanisms and virulence attributes in Candida albicans . Arch Microbiol 198, 459–472 (2016). https://doi.org/10.1007/s00203-016-1205-9

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