Abstract
There is an increasing burden of multidrug resistance. As a result, deciphering the mechanisms of action of natural compounds with antifungal activity has gained considerable prominence. We aimed to elucidate the probable mechanism of action of citronellal, a monoterpenoid found in the essential oil extracted from Cymbopogon plants, against Candida albicans. Drug susceptibility was measured by broth microdilution and spot assays. Ergosterol levels were estimated using the alcoholic potassium hydroxide method and H+ extrusion was assessed by monitoring the glucose-induced acidification of the external medium. Virulence traits were studied by hyphal morphogenesis and biofilm formation, along with fungal cell adherence to polystyrene surface and human oral epithelial cells. Citronellal showed anticandidal activity against C. albicans and non-albicans species of Candida at a minimum inhibitory concentration of 1 mg/ml. Citronellal interfered with membrane homeostasis, which is the major target of known antifungal drugs, by increasing the hypersensitivity of the fungi to membrane-perturbing agents, reducing ergosterol levels, and diminishing glucose-induced H+ extrusion. In addition, oxidative and genotoxic stresses were induced via an increased production of reactive oxygen species. Furthermore, citronellal inhibited the virulent attributes of yeast-to-hypha transition and biofilm formation. It also reduced cell adherence to polystyrene surface and the human oral epithelial cells. This is the first study to propose the cell membrane, morphogenetic switching, biofilm formation, and cell adherence of Candida albicans as potential targets for the anticandidal activity of citronellal. However, clinical investigations on the therapeutic applications of citronellal are required.
Highlights
There is an increasing burden of multidrug resistance
Data from the broth microdilution assay revealed that Cit showed an antifungal activity against C. albicans at an minimal inhibitory concentration (MIC) of 1mg/ml (Figure 1A)
The MIC determined by broth microdilution assay was 1.2mg/ml (Figure 1A), which was further confirmed with a spot assay (Figure 1B)
Summary
There is an increasing burden of multidrug resistance. As a result, deciphering the mechanisms of action of natural compounds with antifungal activity has gained considerable prominence. Citronellal interfered with membrane homeostasis, which is the major target of known antifungal drugs, by increasing the hypersensitivity of the fungi to membrane-perturbing agents, reducing ergosterol levels, and diminishing glucose-induced H+ extrusion. Conclusions: This is the first study to propose the cell membrane, morphogenetic switching, biofilm formation, and cell adherence of Candida albicans as potential targets for the anticandidal activity of citronellal. In the search for novel antifungal drugs, compounds from natural sources are recognized as safer and more promising alternatives to synthetic agents(5) (6). It has been suggested in several studies that various natural compounds are effective against C. albicans. The antifungal activity of geraniol, which is a monoterpenoid compound, was established(9)
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