Efflux in fungi: la pièce de résistance

Abstract

Pathogens must be able to overcome both host defenses and antimicrobial treatment in order to successfully infect and maintain colonization of the host. One way fungi accomplish this feat and overcome intercellular toxin accumulation is efflux pumps, in particular ATP-binding cassette transporters and transporters of the major facilitator superfamily. Members of these two superfamilies remove many toxic compounds by coupling transport with ATP hydrolysis or a proton gradient, respectively. Fungal genomes encode a plethora of members of these families of transporters compared to other organisms. In this review we discuss the role these two fungal superfamilies of transporters play in virulence and resistance to antifungal agents. These efflux transporters are responsible not only for export of compounds involved in pathogenesis such as secondary metabolites, but also export of host-derived antimicrobial compounds. In addition, we examine the current knowledge of these transporters in resistance of pathogens to clinically relevant antifungal agents.

Figure 1. Schematic representation of the two main fungal transporters responsible for efflux of toxic compounds.

Representation of an ABC transporter of the PDR family (A) and an MFS transporter of the DHA12 family (B). The NBDs of the ABC transporter are depicted in red, while the TMDs important for substrate specificity are colored green and gold for the ABC and MFS transporters, respectively.