One of the key mechanisms that confers drug resistance in bacteria involves the action of energyconsuming transporters that drive the efflux of toxic compounds from the cell. In the Gramnegative group of bacteria, which have a characteristic system of two lipid membranes, some of these transporters are the engine components of tripartite assemblies that span both membranes and the interstitial periplasm. These assemblies have been the focus of extensive structural and mechanistic studies for decades, and we provide a brief synopsis of the current understanding of how they are organized into functioning machines, how those machines might work in detail and the likely points in the machinery that could be targets for therapeutic intervention.

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