Interaction of Candida albicans with Fluconazole/ Clotrimazole: Effect on Hyphae Formation and Expression of Hyphal Wall Protein 1

Background and Aims:Candida albicans(C.albicans) is the most common opportunistic human pathogen.Therapeutic options for Candida infectionsare limited to available antifungal drugs.The aim of this study was to investigate the effects of fluconazole/clotrimazole (FLU/CLT) on C. albicanshyphae formation.Materials and Methods:We have established the effectiveness of the combination of FLU/CLTon C. albicanshyphae formation. Interaction of C. albicanswith combination of FLU/CLTwasperformed using the CLSI guidelines and time-killing curves.We investigated the anti-hyphal activities of combination of FLU/CLT against C. albicansusing XTT and crystal violet assays as well as scanning electron microscopy and expression of HWP1gene.Results:The interaction of C. albicanswith FLU/CLTresulted in synergistic, partial synergistic and indifferent effects. The interaction of FLU/CLT were confirmed by time-killing curves.FLU/CLTcombinedresulted in the reduction of metabolic activity and hyphae formation in C.albicans. Images taken by scanning electron microscopy indicated the effectiveness on hyphae disruption. According to relative real time polymerase chain reaction analysis, the mean Ct valuesrevealed the significant decrease in expression level of the HWP1gene. A 2.86-and 2.33-fold decrease in HWP1gene expression was observed in combination of FLU/CLT treatment at 2×minimum inhibitory concentrationand 1×minimum inhibitory concentration, respectively (p=0.002). Conclusions: We confirmed that the hyphae is a target for the combination of FLU/CLTinC.albicans.HWP1gene is likely to be considered as a probable targets synergistic interaction of FLU/CLT againstC.albicans.