Antibiofilm Activity of Farnesol Associated With Tyrosol Against Candida Species

Objectives: The aim of this study was to assess the effect of farnesol in combination with tyrosol against single and mixed biofilms formed by Candida albicans and Candida glabrata in vitro.
Methods: The effect of the drug combination against each strain in planktonic state was determined by minimum inhibitory concentration and checkerboard assays. Candida biofilms were developed within 96-well plates, during 24 h. After, treatments with farnesol and tyrosol, alone or in combination, were performed twice a day for 1 minute, during three days. The antibiofilm activity was determined by total biomass quantification (crystal violet staining) and metabolic activity evaluation (XTT reduction assay). The effects of chlorhexidine gluconate, farnesol and tyrosol alone were used as positive controls. Data were analyzed by one-way ANOVA and Holm-Sidak’s post-hoc test (α = 0.05).
Results: The association of farnesol and tyrosol had a synergic effect on planktonic cells of C. glabrata, with a fractional inhibitory concentration index (FICI) of 0.32. For C. albicans, this effect was classified as indifferent (FICI of 0.6). Regarding total biofilm biomass, farnesol and tyrosol, alone or in combination, promoted significant reductions only for single biofilms of C. glabrata, with reductions ranging from 40 to 57.5%. The highest decrease in biomass was observed for C. glabrata biofilm treated with the drug combination. In addition, drug combination produced the highest decreases in metabolic activity, with significant reductions of 75, 88.7 and 76.3%, respectively for single biofilms of C. albicans and C. glabrata, and mixed biofilms of the two species.
Conclusions: The association of farnesol and tyrosol had a more pronounced effect on C. glabrata than on C. albicans. Future studies should evaluate the action of these drugs in combination on other parameters of biofilm quantification and on other Candida species, aiming to develop adjunctive therapies to control Candida infections.