Citronellal-induced disruption of membrane homeostasis in Candida albicans and attenuation of its virulence attributes

Abstract

Introduction: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. Methods: 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 acidifi cation of the external medium. Virulence traits were studied by hyphal morphogenesis and biofi lm formation, along with fungal cell adherence to polystyrene surface and human oral epithelial cells. Results: 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 biofi lm formation. It also reduced cell adherence to polystyrene surface and the human oral epithelial cells. Conclusions: This is the fi rst study to propose the cell membrane, morphogenetic switching, biofi lm 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.

Essential oils and their components are a class of antifungals with potent vapour-phase-mediated anti-Candida activity

“…glabrata . The activity of citronellal against Candida species has been shown before, and the proposed mode of action is an alteration of membrane homeostasis associated with decreased ergosterol content 43 . On the other hand, the higher susceptibility of C .…”

Insights into the intracellular mechanisms of citronellal in Candida albicans: implications for reactive oxygen species-mediated necrosis, mitochondrial dysfunction, and DNA damage

“…Moreover, Cit induces hypersensitivity in the presence of a DNA damaging agent 4 . Based on DAPI staining, in the presence of Cit, cells showed enhanced fluorescence indicating DNA damage ( Figure 4A) as well as the downregulation of MSH6, a gene involved in DNA repair (Figure 4B).…”

“…Phenotypic susceptibility assays were performed as described elsewhere 4 . Briefly, for the spot assay, 5μL of fivefold serially diluted yeast cultures (cells suspended in normal saline to an OD 600 of 0.1 (1 × 10 6 cells mL -1 ) were spotted on YPD plates in the absence (control) and presence of Cit (250µg mL -1 ).…”

“…It gives the characteristic lemon-scented aroma to citronella oil. The anticandidal potential of Cit has been demonstrated; it primarily targets fungal cell membranes and inhibits virulence traits, such as morphological shifts and biofilm formation, and it may promote the generation of ROS 4 . This study aimed to add to the existing literature about ROS generation in Cit-treated cells and elucidate other potential targets of Cit in C. albicans.…”

A review on genotoxic and mutagenic effects of monoterpenes

“…On the other hand, citronella, a mono terpenoid found in the essential oil extracted from Cymbopogon plants showed an antifungal effect, probably via alteration of membrane homeostasis by increasing the hypersensitivity of the fungi to membraneperturbing agents, reducing ergosterol levels, and diminishing glucose-induced H + extrusion as well as inducing oxidative and genotoxic stresses in Candida albicans (Singh et al 2016).…”