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: Fluconazole (FLC) susceptibility of isolates of Candida spp., (n = 42) and efficacy as well as mechanism of anti-Candida activity of three constituents of geranium oil is evaluated in this study. No fluconazole resistance was observed among the clinical isolates tested, however 22% were susceptible-dose-dependent (S-DD) [minimal inhibitory concentration (MIC) >=16 [mu]g ml-1] and a standard strain of C. albicans ATCC 10231 was resistant (>=64 [mu]g ml-1). Geraniol and geranyl acetate were equally effective, fungicidal at 0.064% v/v concentrations i.e. MICs (561 [mu]g ml-1 and 584 [mu]g ml-1 respectively) and killed 99.9% inoculum within 15 and 30 min of exposures respectively. Citronellol was least effective and fungistatic. C. albicans dimorphism (Y->H) was highly sensitive to geranium oil constituents tested (IC50 approximately 0.008% v/v). Geraniol, geranyl acetate and citronellol brought down MICs of FLC by 16-, 32- and 64-fold respectively in a FLC-resistant strain. Citronellol and geraniol arrested cells in G1 phase while geranyl acetate in G2-M phase of cell cycle at MIC50. In vitro cytotoxicity study revealed that geraniol, geranyl acetate and citronellol were non-toxic to HeLa cells at MICs of the C. albicans growth. Our results indicate that two of the three geranium oil constituents tested exhibit excellent anti-Candida activity and significant synergistic activity with fluconazole.

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