Structural understanding of efflux-mediated drug resistance: potential routes to efflux inhibition |
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Authors: | McKeegan Kenneth S Borges-Walmsley M Ines Walmsley Adrian R |
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Institution: | Centre for Infectious Diseases, Department of Biological Sciences, Wolfson Research Institute, University of Durham Stockton Campus, Stockton-on-Tees TS17 6BH, UK. |
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Abstract: | The active efflux of cytotoxic drugs mediated by multidrug transporters is the basis of multidrug resistance in prokaryotic and eukaryotic cells. Individual multidrug transporters can be extremely versatile, often exhibiting a staggering range of substrate specificity that can negate the effects of clinically relevant therapies. The effective treatment of bacterial, fungal and protozoan infections, along with certain cancer treatments, has been compromised by the presence of multidrug transporters. Traditionally, advances in the understanding of multidrug transporters have been made through biochemical analyses; more recently, however, fundamental advances have been made with the elucidation of several three dimensional structures of representative multidrug pumps. Biochemical and structural analysis of multidrug pumps could lead to the development of novel 'anti-efflux' therapies. |
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