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Microbiology and Molecular Biology Reviews, December 2002, p. 671-701, Vol. 66, No. 4
1092-2172/02/$04.00+0     DOI: 10.1128/MMBR.66.4.671-701.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Regulation of Bacterial Drug Export Systems

Steve Grkovic, Melissa H. Brown, and Ronald A. Skurray*

School of Biological Sciences, University of Sydney, New South Wales 2006, Australia

The active transport of toxic compounds by membrane-bound efflux proteins is becoming an increasingly frequent mechanism by which cells exhibit resistance to therapeutic drugs. This review examines the regulation of bacterial drug efflux systems, which occurs primarily at the level of transcription. Investigations into these regulatory networks have yielded a substantial volume of information that has either not been forthcoming from or complements that obtained by analysis of the transport proteins themselves. Several local regulatory proteins, including the activator BmrR from Bacillus subtilis and the repressors QacR from Staphylococcus aureus and TetR and EmrR from Escherichia coli, have been shown to mediate increases in the expression of drug efflux genes by directly sensing the presence of the toxic substrates exported by their cognate pump. This ability to bind transporter substrates has permitted detailed structural information to be gathered on protein-antimicrobial agent-ligand interactions. In addition, bacterial multidrug efflux determinants are frequently controlled at a global level and may belong to stress response regulons such as E. coli mar, expression of which is controlled by the MarA and MarR proteins. However, many regulatory systems are ill-adapted for detecting the presence of toxic pump substrates and instead are likely to respond to alternative signals related to unidentified physiological roles of the transporter. Hence, in a number of important pathogens, regulatory mutations that result in drug transporter overexpression and concomitant elevated antimicrobial resistance are often observed.

* Corresponding author. Mailing address: School of Biological Sciences, Macleay Building A12, University of Sydney, Sydney, New South Wales 2006, Australia. Phone: 61 2 9351 2376. Fax: 61 2 9351 4771. E-mail: skurray{at}bio.usyd.edu.au.

Microbiology and Molecular Biology Reviews, December 2002, p. 671-701, Vol. 66, No. 4
1092-2172/02/$04.00+0     DOI: 10.1128/MMBR.66.4.671-701.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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Copyright © 2002 by the American Society for Microbiology. All rights reserved.