Mechanisms of multidrug transporters

Authors

  • Henk Bolhuis,

    1. Department of Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Kerklaan 30, NL-9751 NN Haren, The Netherlands
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    • 1Max Planck Institut für Biochemie, Am Klopferspitz 18A, D-82152 Martinsried, Germany.

  • Hendrik W van Veen,

    1. Department of Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Kerklaan 30, NL-9751 NN Haren, The Netherlands
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  • Bert Poolman,

    1. Department of Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Kerklaan 30, NL-9751 NN Haren, The Netherlands
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  • Arnold J.M Driessen,

    1. Department of Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Kerklaan 30, NL-9751 NN Haren, The Netherlands
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  • Wil N Konings

    Corresponding author
    1. Department of Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Kerklaan 30, NL-9751 NN Haren, The Netherlands
      Corresponding author. Tel.: +31 (50) 363 21 50; Fax: +31 (50) 363 21 54; E-mail: W.N.KONINGS@BIOL.RUG.NL
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Corresponding author. Tel.: +31 (50) 363 21 50; Fax: +31 (50) 363 21 54; E-mail: W.N.KONINGS@BIOL.RUG.NL

Abstract

Drug resistance, mediated by various mechanisms, plays a crucial role in the failure of the drug-based treatment of various infectious diseases. As a result, these infectious diseases re-emerge rapidly and cause many victims every year. Another serious threat is imposed by the development of multidrug resistance (MDR) in eukaryotic (tumor) cells, where many different drugs fail to perform their therapeutic function. One of the causes of the occurrence of MDR in these cells is the action of transmembrane transport proteins that catalyze the active extrusion of a large number of structurally and functionally unrelated compounds out of the cell. The mode of action of these MDR transporters and their apparent lack of substrate specificity is poorly understood and has been subject to many speculations. In this review we will summarize our current knowledge about the occurrence, mechanism and molecular basis of (multi-)drug resistance especially as found in bacteria.

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