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Molecular mechanisms of AcrB-mediated multidrug export
Martijn Zwama1, Akihito Yamaguchi2
1Laboratory of Cell Membrane Structural Biology, Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka, 567-0047, Japan; Department of Biomolecular Science and Regulation, Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka, 567-0047, Japan; Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, 565-0871, Japan.
Abstract:
The over-expression of multidrug efflux pumps belonging to the Resistance-Nodulation-Division (RND) superfamily is one of the main causes of multidrug-resistance (MDR) in Gram-negative pathogenic bacteria. AcrB is the most thoroughly studied RND transporter and has functioned as a model for our understanding of efflux-mediated MDR. This multidrug-exporter can recognize and transport a wide range of structurally unrelated compounds (including antibiotics, dyes, bile salts and detergents), while it shows a strict inhibitor specificity. Here we discuss our current knowledge of AcrB, and include recent advances, regarding its structure, mechanism of drug transport, substrate recognition, different intramolecular entry pathways and the drug export driven by remote conformational coupling.
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