Drugs

, Volume 64, Issue 2, pp 159–204 | Cite as

Efflux-Mediated Drug Resistance in Bacteria

Review Article

Abstract

Drug resistance in bacteria, and especially resistance to multiple antibacterials, has attracted much attention in recent years. In addition to the well known mechanisms, such as inactivation of drugs and alteration of targets, active efflux is now known to play a major role in the resistance of many species to antibacterials. Drug-specific efflux (e.g. that of tetracycline) has been recognised as the major mechanism of resistance to this drug in Gram-negative bacteria. In addition, we now recognise that multidrug efflux pumps are becoming increasingly important. Such pumps play major roles in the antiseptic resistance of Staphylococcus aureus, and fluoroquinolone resistance of S. aureus and Streptococcus pneumoniae. Multidrug pumps, often with very wide substrate specificity, are not only essential for the intrinsic resistance of many Gram-negative bacteria but also produce elevated levels of resistance when overexpressed. Paradoxically, ‘advanced’ agents for which resistance is unlikely to be caused by traditional mechanisms, such as fluoroquinolones and β-lactams of the latest generations, are likely to select for overproduction mutants of these pumps and make the bacteria resistant in one step to practically all classes of antibacterial agents. Such overproduction mutants are also selected for by the use of antiseptics and biocides, increasingly incorporated into consumer products, and this is also of major concern. We can consider efflux pumps as potentially effective antibacterial targets. Inhibition of efflux pumps by an efflux pump inhibitor would restore the activity of an agent subject to efflux. An alternative approach is to develop antibacterials that would bypass the action of efflux pumps.

Notes

Acknowledgements

Research in the authors’ laboratory was supported by a grant from the US Public Health Service (AI-09644). A portion of the review is based on the PhD thesis of X.-Z. Li, who thanks Keith Poole for his encouragement during the graduate study in his laboratory. Neither author has any disclosable interest relevant to the content of the review.

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Copyright information

© adis data information BV 2004

Authors and Affiliations

  1. 1.Department of Molecular and Cell BiologyUniversity of CaliforniaBerkeleyUSA

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