Inhibitors of Multidrug Resistant Efflux Systems in Bacteria

Resistance of bacteria to many classes of antibiotics is an increasing problem worldwide. Multidrug resistance efflux pumps are recognized as an important component of resistance in both Gram-positive and Gram-negative bacteria. Some bacterial efflux pumps may be selective for one substrate, such as tetracycline, or transport antibiotics of different classes, conferring a multiple drug resistance (MDR) phenotype. Efflux pump inhibitors (EPIs) are promising therapeutic agents, as they should restore the activity of standard antibiotics. The efflux pump inhibitor-antibiotic combination is expected to increase the intracellular concentration of antibiotics that are expelled by efflux pumps, decrease the intrinsic bacterial resistance to antibiotics, reverse the acquired resistance associated with efflux pumps overexpression, and reduce the frequency of the emergence of resistant mutant strains. In recent years, different classes of EPIs have been described and tested, including analogues of antibiotic substrates and new molecules. This review focuses on the families of MDR efflux pumps, and on the current progress for the clinical use of EPIs. The present article is a good review of the recent patents related to efflux pump inhibitors.