Preventing drug access to targets: cell surface permeability barriers and active efflux in bacteria.
Bacteria, being unicellular, are constantly exposed to toxic compounds in their environment. Gram-negative bacteria and mycobacteria are unusually successful in surviving in the presence of toxic compounds because they combine two mechanisms of resistance. They produce effective permeability barriers, comprising the outer membrane and the mycolate-containing cell wall, on the cell surface. Further, they actively pump out drug molecules that trickle through the barrier, often utilizing multidrug efflux pumps. In Gram-negative bacteria, multidrug pumps of exceptionally wide specificity frequently interact with outer membrane channels and accessory proteins, forming multisubunit complexes that extrude drug molecules directly into the medium, bypassing the outer membrane barrier.
Nikaido
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Department of Molecular and Cell Biology, University of California, 229 Stanley Hall, Berkeley, CA 94720-3206, USA. nhiroshi@uclink4.berkeley.edu
D001693:Biological Transport, Active; D002352:Carrier Proteins; D002463:Cell Membrane Permeability / Q000502:physiology; D004352:Drug Resistance, Microbial; D018432:Drug Resistance, Multiple; D006090:Gram-Negative Bacteria / Q000502:physiology; D008565:Membrane Proteins / Q000502:physiology; D009159:Mycobacteriaceae / Q000502:physiology
D002352:Carrier Proteins; D008565:Membrane Proteins