Abstract
Candida spp. is a significant cause of topical and fungal infections in humans. In addition to Candida albicans, many non-albicans species such as C. krusei, C. glabrata, C. parapsilosis, C. tropicalis, C. guilliermondii cause severe infections. The main antifungal agents belong to three different classes, including azoles, polyenes, and echinocandins. However, resistance to all three categories of drugs has been reported. Therefore, there is an urgent need to search for other alternatives with antifungal activity. Many herbal extracts and compounds from natural sources show excellent antifungal activity. In this study, we used an oil extract from the fruits of Zanthoxylum armatum, which showed significant antifungal activity against various Candida spp. by two different methods—minimum inhibitory concentration (MIC) and agar diffusion. In addition, we attempted to explore the possible mechanism of action in C. albicans. It was found that the antifungal activity of Z. armatum oil is fungicidal and involves a decrease in the level of ergosterol in the cell membrane. The decrease in ergosterol level resulted in increased passive diffusion of a fluorescent molecule, rhodamine6G, across the plasma membrane, indicating increased membrane fluidity. The oil-treated cells showed decreased germ tube formation, an important indicator of C. albicans’ virulence. The fungal cells also exhibited decreased attachment to the buccal epithelium, the first step toward invasion, biofilm formation, and damage to oral epithelial cells. Interestingly, unlike most antifungal agents, in which the generation of reactive oxygen species is responsible for killing, no significant effect was observed in the present study.
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Acknowledgements
We are thankful to Prof Joachim Morschhäuser (Würzburg, Germany) for providing the C. albicans fluconazole-resistant cultures. We also acknowledge Mamta Saini for helping in completion of this study.
Funding
R. Pasrija received funding from Science & Engineering Research Board (SERB) (CRG/2020/004986) under the Department of Science and Technology and Maharshi Dayanand University, Radhakrishnan (R.K.Fund) minor research project (Sanctioned amount: Rs. 50,000).
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R.Pasrija conceived and designed the experiments. D. Kumari and S. Wadhwan conducted the experiments and analyzed the data. R.Pasrija, and V. Mittal wrote the manuscript. R.Pasrija, A. K. Chhillar, and V. Mittal analyzed the data.
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Pasrija, R., Kumari, D., Wadhwan, S. et al. The Zanthoxylum armatum fruit’s oil exterminates Candida cells by inhibiting ergosterol biosynthesis without generating reactive oxygen species. Int Microbiol 27, 423–434 (2024). https://doi.org/10.1007/s10123-023-00401-w
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DOI: https://doi.org/10.1007/s10123-023-00401-w