Overcoming Fungal Multidrug Resistance by Natural Compounds Targeting Efflux Pumps

Since ages, fungal pathogens are exploiting the human host by causing superficial to deep-seated fungal infections. Candida albicans, being the most prevalent pathogen, accounts for approximately 50–60% or more causes of candidiasis in humans leading to alarming mortality worldwide. In spite of significant advances being made in the improvement of antifungal drugs, only limited number of antifungal drugs are currently available and that too are not able to keep pace with the evolution and development of multidrug resistance (MDR) in C. albicans. Among the several causes of MDR, overexpression of drug efflux pumps contributes majorly to MDR. Thus, blocking or modulating the function of the drug efflux pumps still represents an attractive approach to combat MDR. The natural sources have the plethora of many promising natural compounds which can efficiently be exploited to improve the antifungal therapeutics. There is a need to unravel the intrinsic studies on natural inhibitors of efflux pumps. This book chapter unfolds the role of such natural compounds that target drug efflux pumps (the major culprits of MDR) thereby having the potential to chemosensitize towards known antifungal drugs.

Keywords: ABC transporters, Candida, CaMdr1p, Cdr1p, Efflux pumps, Efflux pump inhibitors, Fluconazole, MDR, MFS transporters, Natural compounds.