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Structure and Function of Multidrug Transporters

  • Chapter
Resolving the Antibiotic Paradox

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 456))

Abstract

Toxic compounds have always been part of the natural environment in which microorganisms dwell. The development of strategies for life in this habitat has been crucial for survival of the cell. As a result, microorganisms have developed versatile mechanisms to resist antibiotics and other cytotoxic drugs. Examples are the enzymatic degradation or inactivation of drugs (Davies, 1994), and the alteration of drug targets (Spratt, 1994). In addition, microorganisms possess membrane proteins which catalyze transmembrane drug transport, and hence, are able to overcome cell cytotoxicity by lowering the cytoplasmic drug concentration (Lewis, 1994; Balzi and Goffeau, 1994; Borst and Ouellette, 1995). Some of these drug transporters are fairly specific for a given drug or class of drugs, but the so-called multidrug transporters have specificity for compounds with very different chemical structures and cellular targets. Microbial multidrug transporters can be amplified in drug resistant pathogenic microorganisms, and can shift their drug profiles, making them a menace to drug treatment. Multidrug transporters are also found in mammals, in which they are a cause of multidrug resistance of tumor cells. The structure and function of multidrug transporters is conserved from bacteria to man. On the basis of bioenergetic and structural criteria, multidrug transport systems can be divided into two major classes, Secondary transporters mediate the extrusion of drugs from the cell in a coupled exchange with ions (Paulsen et al, 1996a). ATP-binding cassette [ABC] transporters utilize the release of phosphate bond-energy by ATP hydrolysis, to pump drugs out of the cell (Higgins, 1992).

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Authors and Affiliations

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

    Hendrik W. van Veen & Wil N. Konings

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  1. Hendrik W. van Veen
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  2. Wil N. Konings
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  1. Wayne State University, Detroit, Michigan, USA

    Barry P. Rosen  & Shahriar Mobashery  & 

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van Veen, H.W., Konings, W.N. (1998). Structure and Function of Multidrug Transporters. In: Rosen, B.P., Mobashery, S. (eds) Resolving the Antibiotic Paradox. Advances in Experimental Medicine and Biology, vol 456. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4897-3_8

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  • DOI: https://doi.org/10.1007/978-1-4615-4897-3_8

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  • Print ISBN: 978-1-4613-7220-2

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