Drug resistance in yeasts--an emerging scenario

Abstract

In view of the increasing threat posed by fungal infections in immunocompromised patients and due to the non-availability of effective treatments, it has become imperative to find novel antifungals and vigorously search for new drug targets. Fungal pathogens acquire resistance to drugs (antifungals), a well-established phenomenon termed multidrug resistance (MDR), which hampers effective treatment strategies. The MDR phenomenon is spread throughout the evolutionary scale. Accordingly, a host of responsible genes have been identified in the genetically tractable budding yeast Saccharomyces cerevisiae, as well as in a pathogenic yeast Candida albicans. Studies so far suggest that, while antifungal resistance is the culmination of multiple factors, there may be a unifying mechanism of drug resistance in these pathogens. ABC (ATP binding cassette) and MFS (major facilitator superfamily) drug transporters belonging to two different superfamilies, are the most prominent contributors to MDR in yeasts. Considering the abundance of the drug transporters and their wider specificity, it is believed that these drug transporters may not exclusively export drugs in fungi. It has become apparent that the drug transporters of the ABC superfamily of S. cerevisiae and C. albicans are multifunctional proteins, which mediate important physiological functions. This review summarizes current research on the molecular mechanisms underlying drug resistance, the emerging regulatory circuits of MDR genes, and the physiological relevance of drug transporters.