title: Insights into the mode of action of anticandidal herbal monoterpenoid geraniol reveal disruption of multiple MDR mechanisms and virulence attributes in Candida albicans.
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.
authors.affiliation: Amity Institute of Biotechnology, Amity University Haryana, Manesar, Gurgaon, 122413, India.
authors.forename: Shweta
authors.initials: S
authors.lastname: Singh
authors.affiliation: Amity Institute of Biotechnology, Amity University Haryana, Manesar, Gurgaon, 122413, India.
authors.forename: Zeeshan
authors.initials: Z
authors.lastname: Fatima
authors.affiliation: Amity Institute of Biotechnology, Amity University Haryana, Manesar, Gurgaon, 122413, India. saifhameed@yahoo.co.in.
authors.forename: Saif
authors.initials: S
authors.lastname: Hameed
mesh_terms: D000080462:Acyclic Monoterpenes; D000935:Antifungal Agents / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects* / Q000472:pathogenicity; D002473:Cell Wall / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D025301:Hyphae / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013729:Terpenes / Q000494:pharmacology*; D014774:Virulence / Q000187:drug effects*
chemical_list: D000080462:Acyclic Monoterpenes; D000935:Antifungal Agents; D013729:Terpenes; C007836:geraniol
keywords: Calcineurin signaling; Candida; Cell membrane, biofilm; Cell wall; Geraniol; MDR