Alteration of Azole-Resistant Candida albicans Cell Permeability by a Flavonoid from Dalea elegans

Abstract

Background: The flavonoid 2′,4′-dihydroxy-5′-(1′′′,1′′′-dimethylalil)-8-prenylpinocembrin (8PP), obtained from Dalea elegans roots has demonstrated antifungal activities. It also overcomes the resistance to azoles in azole-resistant Candida albicans (RCa). It collaborates with fluconazole to decrease cell growth and viability and inhibits ABC cdr transporters at the carrying site and associated ATPase. In addition, 8PP reduces cell viability dependent on oxidoreductase activity in planktonic cultures. It shows a dual oxidant-antioxidant activity with accumulating endogenous reactive oxygen species (ROS) in RCa biofilms. Objectives: This work evaluated the effects of 8PP, fluconazole, and their combination on RCa viability, which is dependent on cell permeability. Methods: RCa 12 - 99 strain of oral origin was used. Its viability was assessed through propidium iodide (PI) cell uptake and observing yeast morphology by fluorescence microscopy. Results: RCa 12 - 99 strain cells, collected in the mid-exponential phase, incorporated PI and completely stained red after incubation with 8PP or fluconazole at concentrations that inhibit cell growth and viability. When combined at 125 µM of each, 8PP and fluconazole appeared more effective than separately. The results indicated that the compounds tested impaired cell permeability directly or indirectly. Conclusions: 8PP and fluconazole and their combination caused alterations in cell permeability in azole-resistant Candida albicans. They were effective both individually and in combination.