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JAC Advance Access originally published online on December 4, 2006
Journal of Antimicrobial Chemotherapy 2007 59(6):1247-1260; doi:10.1093/jac/dkl460
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© The Author 2006. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Special section: Efflux

Bacterial efflux pump inhibitors from natural sources

Michael Stavri1, Laura J. V. Piddock2 and Simon Gibbons1,*

1 Centre for Pharmacognosy and Phytotherapy, The School of Pharmacy, University of London 29-39 Brunswick Square, London WC1N 1AX, UK 2 Antimicrobial Agents Research Group, Division of Immunity and Infection, The Medical School, University of Birmingham Birmingham B15 2TT, UK

*Corresponding author. Tel: +44-207-7535913; Fax: +44-207-7535909; E-mail: simon.gibbons{at}pharmacy.ac.uk

The rapid spread of bacteria expressing multidrug resistance (MDR) has necessitated the discovery of new antibacterials and resistance-modifying agents. Since the initial discovery of bacterial efflux pumps in the 1980s, many have been characterized in community- and hospital-acquired Gram-positive and Gram-negative pathogens, such as Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and, more recently, in mycobacteria. Efflux pumps are able to extrude structurally diverse compounds, including antibiotics used in a clinical setting; the latter are rendered therapeutically ineffective. Antibiotic resistance can develop rapidly through changes in the expression of efflux pumps, including changes to some antibiotics considered to be drugs of last resort. It is therefore imperative that new antibiotics, resistance-modifying agents and, more specifically, efflux pump inhibitors (EPIs) are characterized. The use of bacterial resistance modifiers such as EPIs could facilitate the re-introduction of therapeutically ineffective antibiotics back into clinical use such as ciprofloxacin and might even suppress the emergence of MDR strains. Here we review the literature on bacterial EPIs derived from natural sources, primarily those from plants. The resistance-modifying activities of many new chemical classes of EPIs warrant further studies to assess their potential as leads for clinical development.

Keywords: MDR , MRSA , Staphylococcus aureus , NorA, efflux , Mycobacterium , Pseudomonas , Escherichia , modulators


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