PMID:7651136

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Citation

Ma, D, Cook, DN, Alberti, M, Pon, NG, Nikaido, H and Hearst, JE (1995) Genes acrA and acrB encode a stress-induced efflux system of Escherichia coli. Mol. Microbiol. 16:45-55

Abstract

Defined mutations of acrA or acrB (formerly acrE) genes increased the susceptibility of Escherichia coli to a range of small inhibitor molecules. Deletion of acrAB increased susceptibility to cephalothin and cephaloridine, but the permeability of these beta-lactams across the outer membrane was not increased. This finding is inconsistent with the earlier hypothesis that acrAB mutations increase drug susceptibility by increasing the permeability of the outer membrane, and supports our model that acrAB codes for a multi-drug efflux pump. The natural environment of an enteric bacterium such as E. coli is enriched in bile salts and fatty acids. An acrAB deletion mutant was found to be hypersusceptible to bile salts and to decanoate. In addition, acrAB expression was elevated by growth in 5 mM decanoate. These results suggest that one major physiological function of AcrAB is to protect E. coli against these and other hydrophobic inhibitors. Transcription of acrAB is increased by other stress conditions including 4% ethanol, 0.5 M NaCl, and stationary phase in Luria-Bertani medium. Finally, acrAB expression was shown to be increased in mar (multiple-antibiotic-resistant) mutants.

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Keywords

Acriflavine/pharmacology; Anti-Bacterial Agents/pharmacology; Bacterial Proteins/biosynthesis; Bacterial Proteins/genetics; Bacterial Proteins/physiology; Biological Transport, Active; Carrier Proteins; Cell Membrane Permeability; Cholic Acids/pharmacology; Drug Resistance, Multiple/genetics; Escherichia coli/drug effects; Escherichia coli/genetics; Escherichia coli/growth & development; Escherichia coli/metabolism; Escherichia coli Proteins; Fatty Acids/pharmacology; Gene Expression Regulation, Bacterial; Lipoproteins/biosynthesis; Lipoproteins/genetics; Lipoproteins/physiology; Membrane Proteins/biosynthesis; Membrane Proteins/genetics; Membrane Proteins/physiology; Membrane Transport Proteins; Microbial Sensitivity Tests; Multidrug Resistance-Associated Proteins; Mutagenesis, Insertional; Operon; P-Glycoprotein; Sodium Dodecyl Sulfate/pharmacology; Time Factors

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