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Background  Farnesol has potential antifungal activity against  Candida albicans  biofilms, but the molecular mechanism of this activity is still unclear. Farnesol inhibits hyphal growth by regulating the cyclic AMP (cAMP) signalling pathway in  C. albicans , and  CYR1  and  PDE2  regulate a pair of enzymes that are directly responsible for cAMP synthesis and degradation. Here, we hypothesize that farnesol enhances the antifungal susceptibility of  C. albicans  biofilms by regulating  CYR1  and  PDE2 .    Results  The resistance of the  CYR1 - and  PDE2 -overexpressing strains to caspofungin, itraconazole and terbinafine was increased in planktonic cells, and that to amphotericin B was increased in biofilms. Meanwhile, the biofilms of the  CYR1 - and  PDE2 -overexpressing strains were thicker (all  p  < 0.05) and consisted of more hyphae than that of the wild strain. The intracellular cAMP levels were higher in the biofilms of the  CYR1 -overexpressing strain than that in the biofilms of the wild strain (all  p  < 0.01), while no changes were found in the  PDE2 -overexpressing strain. Exogenous farnesol decreased the resistance of the  CYR1 - and  PDE2 -overexpressing strains to these four antifungals, repressed the hyphal and biofilm formation of the strains, and decreased the intracellular cAMP level in the biofilms (all  p  < 0.05) compared to the untreated controls. In addition, farnesol decreased the expression of the gene  CYR1  and the protein CYR1 in biofilms of the  CYR1 -overexpressing strain (all  p  < 0.05) but increased the expression of the gene  PDE2  and the protein PDE2 in biofilms of the  PDE2 -overexpressing strain (all  p  < 0.01).    Conclusions  The results indicate that  CYR1  and  PDE2  regulate the resistance of  C. albicans  biofilms to antifungals. Farnesol suppresses the resistance of  C. albicans  biofilms to antifungals by regulating the expression of the gene  CYR1  and  PDE2 , while  PDE2  regulation was subordinate to  CYR1  regulation.

The possible molecular mechanisms of farnesol on the antifungal resistance of C. albicans biofilms: the regulation of CYR1 and PDE2