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Proton-dependent multidrug efflux systems

I T Paulsen1, M H Brown, R A Skurray

  • 1School of Biological Sciences, University of Sydney, New South Wales, Australia.

Microbiological Reviews
|December 1, 1996
PubMed
Summary
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Multidrug efflux systems, crucial for cellular defense, utilize proton motive force to expel diverse drugs. This review details proton-dependent transporters across prokaryotes and eukaryotes, exploring their families, mechanisms, and physiological roles.

Area of Science:

  • Biochemistry and Molecular Biology
  • Cell Biology
  • Microbiology

Background:

  • Multidrug efflux systems confer resistance to various chemotherapeutic agents by exporting structurally unrelated drugs from cells.
  • These systems are vital in both prokaryotic and eukaryotic organisms, impacting cellular defense mechanisms and drug efficacy.

Purpose of the Study:

  • To review proton-dependent multidrug efflux systems, detailing their classification, mechanisms, and substrate specificities.
  • To explore the structural families, distribution, and potential physiological roles of these essential transport proteins.

Main Methods:

  • Review of existing literature on proton-dependent multidrug efflux systems.
  • Analysis of the major facilitator superfamily (MFS), small multidrug resistance (SMR) family, and resistance/nodulation/cell division (RND) family transporters.

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  • Examination of auxiliary proteins involved in efflux in gram-negative bacteria.

    • Main Results:

    • Proton-dependent multidrug efflux proteins are categorized into MFS, SMR, and RND families, each with distinct structural and functional characteristics.
    • MFS proteins can have 12 or 14 transmembrane segments, SMR proteins have 4, and RND proteins have 12, often exhibiting broad substrate specificity.
    • Gram-negative bacteria utilize auxiliary membrane fusion and outer membrane proteins for complete efflux across both membranes.

    Conclusions:

    • Proton-dependent multidrug efflux systems are diverse, widespread, and often present in multiple copies within single organisms, like E. coli.
    • The molecular basis for their broad substrate specificity and their primary physiological function—whether defense or other roles—warrants further investigation.