Farnesol against Coccidioides posadasii : its effect on growth, ergosterol

Abstract

Coccidioidomycosis is a systemic mycosis caused by the dimorphic fungi Coccidioides spp. The treatment for chronic and/or disseminated coccidioidomycosis can be prolonged and complicated. Therefore, the search for new drugs is necessary. Farnesol is a precursor in the sterol biosynthesis pathway that has been shown to present antifungal activity. Thus, the objective of this study was to evaluate the in vitro antifungal activity of farnesol alone and in combination with antifungal agents against clinical and environmental strains of Coccidioides posadasii, as well as to determine their effect on the synthesis of ergosterol and on cell permeability. This study employed the broth macrodilution method to determine the minimum inhibitory concentration (MIC) of farnesol against strains of C. posadasii. Quantification of ergosterol was performed with ten strains of C. posadasii, after the exposure to sub-inhibitory concentrations of farnesol. Finally, the activity of farnesol was evaluated at the presence of osmotic stress, induced by the addition of NaCl to the culture medium, during the susceptibility tests. The results showed that farnesol exhibited low MICs (ranging from 0,00171- 0,01369 mg/L) against all tested strains. The combination of farnesol with the antifungals showed synergistic effects (FICI≤0.5). As for ergosterol quantification, it was observed that exposure to sub-inhibitory concentrations of farnesol decreased the amount of ergosterol extracted from the fungal cells. Furthermore, farnesol also showed lower MIC values when the strains were subjected to osmotic stress, indicating the action of this compound on the fungal membrane. Thus, due to the high in vitro antifungal activity, this work brings perspectives for the performance of in vivo studies to further elucidate the effects of farnesol on the host cells.