The number of dangerous and fatal infections caused by pathogenic Candida yeasts is increasing rapidly every year. One of the biggest problems encountered in treating these infections is the ability of cells to acquire resistance to known antifungal drugs. The most common mechanism of resistance is multidrug resistance pumps. Usually, in resistant strains activity of such pumps is upregulated, leading to increased antifungal drug efflux out of cells. Because of that, the concentrations of drugs within the cells are too low to inhibit the growth of pathogenic Candida yeasts. One possible way to increase the concentrations of antifungals inside the cells is an inhibition of the activity of efflux pumps, using alternative substrates, i.e. drugs used for the treatment of chronic diseases.
The aim of this study was to evaluate the ability of statins - drugs to lower the level of cholesterol in the blood – to inhibit the efflux of antifungals. The effects of statins alone or in combinations with antifungals were tested against different strains of C. glabrata and C. albicans, including strains mutant in ABC family efflux pumps – CDR1 and CDR2. The efficiency of the statins was determined using the microdilution method and electrochemical measurements. The results of our experiments revealed that three of chosen statins (atorvastatin, fluvastatin, and rosuvastatin) at tested concentrations (0,5 - 256 μg/ml) had no fungicidal activity against C. glabrata and C. albicans. At the same time, combinations with known antifungals (fluconazole and nystatin) reduced the growth of tested cells used in this study.
These findings show that statins strengthen the effects of antifungal drugs and might be helpful in the treatment of Candida infections.