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 diseases. As a result, these infectious diseases re-emerge rapidly and cause many victims every year. Another serious threat is imposed by the development of multidrug resistance (MDR) in eukaryotic (tumor) cells, where many different drugs fail to perform their therapeutic function. One of the causes of the occurrence of MDR in these cells is the action of transmembrane transport proteins that catalyze the active extrusion of a large number of structurally and functionally unrelated compounds 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 summarize our current knowledge about the occurrence, mechanism and molecular basis of (multi-)drug resistance especially as found in bacteria.
Bolhuis
H
H
Department of Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Haren, The Netherlands.
van Veen
H W
HW
Poolman
B
B
Driessen
A J
AJ
Konings
W N
WN
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry / Q000502:physiology; D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000502:physiology; D000595:Amino Acid Sequence; D001692:Biological Transport; D002352:Carrier Proteins / Q000502:physiology*; D018432:Drug Resistance, Multiple; D006801:Humans; D008969:Molecular Sequence Data; D013329:Structure-Activity Relationship
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D002352:Carrier Proteins