Assembly and transport mechanism of tripartite drug efflux systems.
Multidrug efflux (MDR) pumps remove a variety of compounds from the cell into the external environment. There are five different classes of MDR pumps in bacteria, and quite often a single bacterial species expresses multiple classes of pumps. Although under normal circumstances MDR pumps confer low-level intrinsic resistance to drugs, the presence of drugs and mutations in regulatory genes lead to high level expression of MDR pumps that can pose problems with therapeutic treatments. This review focuses on the resistance nodulation cell division (RND)-class of MDR pumps that assemble from three proteins. Significant recent advancement in structural aspects of the three pump components has shed new light on the mechanism by which the tripartite efflux pumps extrude drugs. This new information will be critical in developing inhibitors against MDR pumps to improve the potency of prescribed drugs.
Misra
Rajeev
R
Faculty of Cellular and Molecular Biosciences, School of Life Sciences, Arizona State University, Tempe, AZ 85285-4501, USA. rajeev.misra@asu.edu
Bavro
Vassiliy N
VN
D000942:Antigens, Bacterial / Q000737:chemistry; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry; D001692:Biological Transport; D024901:Drug Resistance, Multiple, Bacterial / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000378:metabolism; D008074:Lipoproteins / Q000378:metabolism; D050576:Membrane Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism; D017434:Protein Structure, Tertiary
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D008074:Lipoproteins; D050576:Membrane Fusion Proteins; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D004364:Pharmaceutical Preparations; C083497:AcrA protein, E coli; C083496:AcrB protein, E coli; C116101:YajC protein, Brucella; C073126:tolC protein, E coli