Efflux Pump Inhibitors: A Novel Approach to Combat Efflux-Mediated Drug Resistance in Bacteria

• Published in: Current drug targets Vol. 17; no. 6; p. 702
• Main Authors: Wang, Yinhu, Venter, Henrietta, Ma, Shutao
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01.05.2016
• Subjects: Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Bacterial Infections - drug therapy; Bacterial Proteins - antagonists & inhibitors; Bacterial Proteins - metabolism; Drug Resistance, Multiple, Bacterial - drug effects; Drug Synergism; Gram-Negative Bacteria - drug effects; Gram-Positive Bacteria - drug effects; Humans; Membrane Transport Proteins - metabolism; Structure-Activity Relationship
• ISSN: 1873-5592
• DOI: 10.2174/1389450116666151001103948

The increasing multi-drug resistance has become a major threat to the public health. Overexpression of multidrug efflux pumps is one of the major mechanisms of drug resistance in bacteria. Since active efflux of antibacterial agents plays a significant role in mediating drug resistance in bacteria, the inhibition of efflux pumps appears to be a promising strategy to restore antibacterial potency. In recent years, in order to address this grave problem of multiple drug resistance mediated by efflux pump, a large number of efflux pump inhibitors have been discovered and tested, including natural products, antibiotics and synthetic molecules. This review mainly describes recent achievements in the search for new molecules that are able to inhibit efflux pumps in both Gram-positive and Gram-negative bacteria, in particular emphasis on natural and synthetic inhibitors of the NorA efflux pump in Staphylococcus aureus, MexAB-OprM efflux pump in Pseudomonas aeruginosa, and AcrAB-TolC efflux pump in Enterobacteriaceae, giving special attention to their mechanisms of action, structure-activity relationships and synergetic effect with clinically available antibiotics.