Abstract
Multidrug efflux transporters of the resistance-nodulation-cell division (RND) superfamily are one of the main causes of multidrug resistance (MDR) in Gram-negative bacteria. These proton motive force-dependent transporters generally occur as tripartite efflux complexes that span the cytoplasmic and outer membranes, thus providing a mechanism to directly extrude antimicrobial substrates out of the cell. RND transporters can accommodate an incredibly wide range of antimicrobial agents and play an important role in clinically relevant antimicrobial resistance. The first crystal structure of a multidrug efflux transporter was solved in 2002 for the AcrB RND transporter of Escherichia coli. Subsequently over the last decade, several structures of RND transporters have been successfully crystallized both in the presence and absence of their antimicrobial substrates, providing a fundamental understanding of the structural basis for functional transport mechanisms. This chapter describes the current knowledge of the structural and functional characteristics of RND efflux pumps based on these crystal structures.
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