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


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 biofilm formation. It also reduced cell adherence to polystyrene surface and the human oral epithelial cells.


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. However, clinical investigations on the therapeutic applications of citronellal are required.
Amity Institute of Biotechnology, Amity University Haryana, Gurgaon (Manesar), India.
Shweta
S
Singh
Amity Institute of Biotechnology, Amity University Haryana, Gurgaon (Manesar), India.
Zeeshan
Z
Fatima
Amity Institute of Biotechnology, Amity University Haryana, Gurgaon (Manesar), India.
Saif
S
Hameed
D000080462:Acyclic Monoterpenes; D000447:Aldehydes / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development; D002176:Candida albicans / Q000187:drug effects* / Q000472:pathogenicity; D002448:Cell Adhesion / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D039821:Monoterpenes / Q000494:pharmacology*; D014774:Virulence / Q000187:drug effects*
D000080462:Acyclic Monoterpenes; D000447:Aldehydes; D000935:Antifungal Agents; D039821:Monoterpenes; C108217:citronellal