Prevention of Drug Access to Bacterial Targets: Permeability Barriers and Active Efflux
1994/04/15 by Hiroshi Nikaido · 1,553 citations
Biochemistry, Genetics and Molecular Biology · Medicine · #Antibiotic Resistance in Bacteria #Antibiotic resistance #Antibiotics #Antibiotics Pharmacokinetics and Efficacy #Bacteria #Bacterial outer membrane #Biochemistry #Biology #Drug #Drug Transport and Resistance Mechanisms #Drug resistance #Efflux #Membrane #Membrane permeability #Microbiology #Multiple drug resistance #Pharmacology #Pseudomonas aeruginosa
paper · doi:10.1126/science.8153625
published in Science 264(5157), 382-388 (American Association for the Advancement of Science)
openalex publication_date 1994/04/15 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
Abstract
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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