Efflux-mediated drug resistance in Gram-positive bacteria

Gram-positive bacteria express numerous membrane transporters that promote the efflux of various drugs, including many antibiotics, from the cell to t he outer medium. Drug transporters can be specific to a particular drug, or can have broad specificity, as in so-called multidrug transporters. This b road specificity can be a consequence of the hydrophobic nature of transpor ted molecules, as suggested by recent structural studies of soluble multidr ug-binding proteins. Although the functions of drug transporters may involv e both the protection of bacteria from outside toxins and the transport of natural metabolites, their clinical importance lies largely in providing Gr am-positive pathogens with resistance to macrolides, tetracyclines and fluo roquinolones. A number of agents, discovered in recent years, that inhibit drug transporters can potentially be used to overcome efflux-associated ant ibiotic resistance.