MECHANISMS OF MULTIDRUG TRANSPORTERS

Drug resistance, mediated by various mechanisms, plays a crucial role in the failure of the drug-based treatment of various infectious disea ses. As a result, these infectious diseases re-emerge rapidly and caus e many victims every year. Another serious threat is imposed by the de velopment of multidrug resistance (MDR) in eukaryotic (tumor) cells, w here many different drugs fail to perform their therapeutic function. One of the causes of the occurrence of MDR in these cells is the actio n of transmembrane transport proteins that catalyze the active extrusi on of a large number of structurally and functionally unrelated compou nds out of the cell. The mode of action of these MDR transporters and their apparent lack of substrate specificity is poorly understood and has been subject to many speculations. In this review we will summariz e our current knowledge about the occurrence, mechanism and molecular basis of (multi-)drug resistance especially as found in bacteria.