Evaluation of anti-Candida potential of geranium oil constituents against clinical isolates of Candida albicans differentially sensitive to fluconazole: inhibition of growth, dimorphism and sensitization

• Published in: Mycoses 2011-07, Vol.54 (4), p.e99-e109
• Main Authors: Zore, Gajanan B., Thakre, Archana D., Rathod, V., Karuppayil, S. Mohan
• Format: Article
• Language: English
• Subjects: Acetates - isolation & purification; Acetates - pharmacology; Acetates - toxicity; Antifungal Agents - isolation & purification; Antifungal Agents - pharmacology; Antifungal Agents - toxicity; Candida albicans; Candida albicans - drug effects; Candida albicans - growth & development; Candida albicans - isolation & purification; Candida albicans - pathogenicity; Candidiasis - microbiology; Cell cycle; citronellol; Clinical isolates; Cytotoxicity; Dimorphism; Drug Resistance, Fungal; Epithelial Cells - drug effects; fluconazole; G1 phase; Geraniol; Geranium; Geranium - chemistry; geranium oil; geranyl acetate; HeLa Cells; Humans; Inhibitory Concentration 50; Inoculum; isoprenoids; Microbial Sensitivity Tests; Microbial Viability - drug effects; Minimum inhibitory concentration; Monoterpenes - isolation & purification; Monoterpenes - pharmacology; Monoterpenes - toxicity; Oil; Plant Oils - chemistry; Plant Oils - isolation & purification; Plant Oils - pharmacology; Terpenes - isolation & purification; Terpenes - pharmacology; Terpenes - toxicity
• ISSN: 0933-7407; 1439-0507
• DOI: 10.1111/j.1439-0507.2009.01852.x

Summary 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 μg ml−1] and a standard strain of C. albicans ATCC 10231 was resistant (≥64 μg ml−1). Geraniol and geranyl acetate were equally effective, fungicidal at 0.064% v/v concentrations i.e. MICs (561 μg ml−1 and 584 μg 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.