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Science 15 April 1994:
Vol. 264. no. 5157, pp. 382 - 388
DOI: 10.1126/science.8153625
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Articles

Science, Vol 264, Issue 5157, 382-388
Copyright © 1994 by American Association for the Advancement of Science

articles

Prevention of drug access to bacterial targets: permeability barriers and active efflux

H Nikaido

Department of Molecular and Cell Biology, University of California, Berkeley 94720-3206.

Some species of bacteria have low-permeability membrane barriers and are thereby "intrinsically" resistant to many antibiotics; they are selected out in the multitude of antibiotics present in the hospital environment and thus cause many hospital-acquired infections. Some strains of originally antibiotic-susceptible species may also acquire resistance through decreases in the permeability of membrane barriers. Another mechanism for preventing access of drugs to targets is the membrane-associated energy-driven efflux, which plays a major role in drug resistance, especially in combination with the permeation barrier. Recent results indicate the existence of bacterial efflux systems of extremely broad substrate specificity, in many ways reminiscent of the multidrug resistance pump of mammalian cells. One such system seems to play a major role in the intrinsic resistance of Pseudomonas aeruginosa, a common opportunistic pathogen. As the pharmaceutical industry succeeds in producing agents that can overcome specific mechanisms of bacterial resistance, less specific resistance mechanisms such as permeability barriers and multidrug active efflux may become increasingly significant in the clinical setting.


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Identification and Characterization of Inhibitors of Multidrug Resistance Efflux Pumps in Pseudomonas aeruginosa: Novel Agents for Combination Therapy.
O. Lomovskaya, M. S. Warren, A. Lee, J. Galazzo, R. Fronko, M. Lee, J. Blais, D. Cho, S. Chamberland, T. Renau, et al. (2001)
Antimicrob. Agents Chemother. 45, 105-116
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Identification and molecular characterization of an efflux system involved in Pseudomonas putida S12 multidrug resistance.
J. Kieboom and J. A. M. de Bont (2001)
Microbiology 147, 43-51
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