and anti- activity of citral in combination with fluconazole.

Background: The ability of to develop biofilms on inert surfaces or living tissues favors recalcitrant and chronic candidiasis associated, in many instances, with resistance to current antifungal therapy.

Aim: The aim of this study was to evaluate the antifungal activity of citral, a phytocompound present in lemongrass essential oil, in monotherapy and combined with fluconazole against azole-resistant planktonic cells and biofilms. The effect of citral combined with fluconazole was also analysed with regard to the expression of fluconazole resistance-associated genes in and the effectiveness of the combination therapy in a model of candidiasis.

Results: Citral reduced biofilm formation at initial stages and the metabolic activity of the mature biofilm. The combination of citral with fluconazole was synergistic, with a significant increase in the survival of infected with . RNA analysis revealed a reduction of the expression of the efflux pump encoded by , leading to a greater effect of fluconazole.

Conclusion: Citral in monotherapy and in combination with fluconazole could represent an interesting therapy to treat recalcitrant infections associated to biofilms.