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

Mycoses. 2011 Jul;54(4):e99-109. doi: 10.1111/j.1439-0507.2009.01852.x. Epub 2010 Mar 11.

Abstract

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 MIC(50). 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / isolation & purification
  • Acetates / pharmacology
  • Acetates / toxicity
  • Acyclic Monoterpenes
  • Antifungal Agents / isolation & purification*
  • Antifungal Agents / pharmacology*
  • Antifungal Agents / toxicity
  • Candida albicans / drug effects*
  • Candida albicans / growth & development
  • Candida albicans / isolation & purification
  • Candida albicans / pathogenicity
  • Candidiasis / microbiology
  • Drug Resistance, Fungal*
  • Epithelial Cells / drug effects
  • Geranium / chemistry*
  • HeLa Cells
  • Humans
  • Inhibitory Concentration 50
  • Microbial Sensitivity Tests
  • Microbial Viability / drug effects
  • Monoterpenes / isolation & purification
  • Monoterpenes / pharmacology
  • Monoterpenes / toxicity
  • Plant Oils / chemistry*
  • Plant Oils / isolation & purification
  • Plant Oils / pharmacology*
  • Terpenes / isolation & purification
  • Terpenes / pharmacology
  • Terpenes / toxicity

Substances

  • Acetates
  • Acyclic Monoterpenes
  • Antifungal Agents
  • Monoterpenes
  • Plant Oils
  • Terpenes
  • geranyl acetate
  • geraniol
  • citronellol