In Vitro Effects of Farnesol Alone and in Combination with Antifungal Drugs Against Aspergillus Clinical Isolates

Med Mycol J. 2021;62(1):5-10. doi: 10.3314/mmj.20-00016.

Abstract

Farnesol is an extracellular quorum-sensing molecule produced by Candida albicans. Farnesol is also a sesquiterpene alcohol existing in many herbal products and has various activity against fungal cells. We aimed to investigate the efficacy of farnesol alone and the contribution of farnesol on the activity of voriconazole and amphotericin B against Aspergillus clinical isolates in vitro. A total of 45 Aspergillus clinical isolates were used in this study. The MIC values of voriconazole, amphotericin B, and farnesol were determined using reference broth microdilution method. The interactions of farnesol with voriconazole and amphotericin B were investigated by the checkerboard method and evaluated based on the fractional inhibitor concentration index (FICI). The MIC ranges of farnesol, voriconazole, and amphotericin B were 1,500-6,000 μM, 0.125-1 μg/mL, and 0.125-0.5 μg/mL against Aspergillus fumigatus isolates, 3,000-12,000 μM, 0.125-0.5 μg/mL, and 0.25-2 μg/mL against Aspergillus flavus isolates, respectively. The most common interaction in combination tests was "no interaction," and synergistic interaction was not detected. The combinations of farnesol with voriconazole and amphotericin B had antagonistic activity against 38% and 27% of all isolates, respectively.We concluded that the responses of different fungal species against farnesol are variable, and different interactions may be observed when it is combined with different antifungals. Therefore, it should be noted that farnesol may have an adverse effect on some fungi or interact negatively with antifungals used in combination.

Keywords: Aspergillus; amphotericin B; antifungal activity; farnesol; voriconazole.

MeSH terms

  • Amphotericin B / pharmacology*
  • Antifungal Agents / pharmacology*
  • Aspergillus / drug effects*
  • Aspergillus / isolation & purification
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Drug Interactions
  • Drug Resistance, Fungal
  • Drug Synergism
  • Farnesol / adverse effects
  • Farnesol / pharmacology*
  • Humans
  • Voriconazole / pharmacology*

Substances

  • Antifungal Agents
  • Drug Combinations
  • Farnesol
  • Amphotericin B
  • Voriconazole