Inhibition of Candida albicans yeast– hyphal transition by combination of fluconazole with amphotericin B

Candidiasis represents a major threat to the life and health in immune-compromised individuals. The number of antifungal drugs is limited for the treatment of candidiasis. Combination therapy is one of the most frequently used techniques to alleviate this problem. Clinical isolates of Candida albicans were obtained from the immune-compromised patients. Antifungal susceptibilities to fluconazole and amphotericin B alone and in combination were performed by broth microdilution method. Eventually direct microscopic observation, time-kill kinetic assay, biomass and metabolic activity of the hypha, Sap enzyme activity and expression of SAP3 gene were carried out in C. albicans. Combination of fluconazole with amphotericin B demonstrated synergistic and partial synergistic effects with fractional inhibitory concentration index ranged from 0.031 to 0.75. The data indicated that combination of fluconazole with amphotericin B exerted antifungal effects through reducing time-kill kinetic, yeast– hyphal transition, biomass and metabolic activity of the hypha and Sap enzyme activity in C. albicans. Additionally, the expression levels of the SAP3 gene were significantly down regulated (P<0.001) in C. albicans treated with combination of fluconazole with amphotericin B. Taken together, these events may confirm the potential uses of combination of fluconazole with amphotericin B against C. albicans. The results suggest that SAP3 gene could be probable target of synergistic interaction of fluconazole and amphotericin B in C. albicans.