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

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.

Combination of Farnesol with Common Antifungal Drugs: Inhibitory Effect against Clinical Isolates of <em>Candida</em> Species

“…As a result, the search for efficient agents antifungal with minimum side effects and low toxicity is highly recommended [32]. Besides, the efficacy of conventional drugs is often undesirable due to their high toxicity, low tolerability, or narrow spectrum of action [15]. Hence, the abovementioned issues have encouraged researchers to explore novel antifungal agents, even though combination therapies to overcome therapeutic failure of VVC in women infected with resistant Candida species which led to recurrent VVC as well as economic burden in health care system.…”

“…Some studies have reported that farnesol inhibits hyphae formation, has antioxidant effects, also inhibiting drug transporters. Moreover, previously published data proposed that farnesol has in vitro synergistic effects with various antifungals like nystatin, itraconazole and fluconazole [14,15]. Furthermore, this signaling molecule was observed to inhibit biofilm formation and in combination with certain antifungals, farnesol can serve as an adjuvant in therapy of candidiasis [16].…”

Combination of Farnesol with Common Antifungal Drugs: Inhibitory Effect against Candida Species Isolated from Women with RVVC

“…Some studies have reported that farnesol inhibits hyphae formation, also inhibiting drug transporters [14][15][16][17]. Published data have proposed that farnesol has in vitro synergistic effects with various antifungals such as nystatin, itraconazole, fluconazole, amphotericin B, and echinocandins [18,19]. Furthermore, this signaling molecule was observed to inhibit the biofilm formation, and in combination with certain antifungals, farnesol can even serve as an adjuvant in the therapy of candidiasis [20].…”

Intracellular production of reactive oxygen species and a DAF-FM-related compound in Aspergillus fumigatus in response to antifungal agent exposure

“…This compound acts as a quorum-sensing molecule in C. albicans and is involved in the inhibition of the yeast-to-hypha transition 10 , thereby blocking biofilm formation 11 . It has been linked to significant fungal growth alterations, such as conidiation inhibition, growth retardation, and apoptosis-like cell death, in several species of pathogenic fungi 12 – 15 .…”