Using yeast to discover inhibitors of multidrug efflux in Candida albicans

Abstract

Fungal infections range from mild readily treated conditions such athlete's foot or thrush to life-threatening illnesses that affect immunocompromised or immunosuppressed patients. The antimycotic azole drugs, which target the enzyme lanosterol 14a-demethylase required for ergosterol biosynthesis, have provided therapy for a wide range of fungal infections over several decades. However, significant resistance is conferred by the removal of azole drugs from fungal cells via multidrug efflux pumps belong to the ABCG class of ATP-binding cassette transporters and a DHA1 class major facilitator superfamily efflux pump. This chapter will describe how the genetically tractable and biochemically well-characterised yeast Saccharomyces cerevisiae has provided a platform for the discovery and testing of novel inhibitors of these two classes of drug efflux pump in fungal pathogens of humans.