PMID:19734019

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Citation

Martins, A, Iversen, C, Rodrigues, L, Spengler, G, Ramos, J, Kern, WV, Couto, I, Viveiros, M, Fanning, S, Pages, JM and Amaral, L (2009) An AcrAB-mediated multidrug-resistant phenotype is maintained following restoration of wild-type activities by efflux pump genes and their regulators. Int. J. Antimicrob. Agents 34:602-4

Abstract

In this study, we aimed to answer the following question: 'How does a bacterium become so resistant to a given antibiotic even though the levels of antibiotic to which it has become resistant remained constant in the patient?'Escherichia coli AG100 strain induced to high-level resistance due to overexpression of an AcrAB efflux pump was serially cultured in 10mg/L tetracycline for 60 passages. Between each passage it became increasingly resistant to tetracycline, beta-lactams and quinolones with concomitant restoration of wild-type AcrAB activity. Because the multidrug-resistant phenotype could not be reversed with transfer to drug-free medium or with efflux pump inhibitors, it may have resulted from activation of a 'mutator gene' system that reduced the 'energy consumption' associated with an overexpressed efflux pump system.

Links

PubMed Online version:10.1016/j.ijantimicag.2009.06.029

Keywords

Adaptation, Biological; Anti-Bacterial Agents/metabolism; Anti-Bacterial Agents/pharmacology; Drug Resistance, Multiple, Bacterial; Escherichia coli/drug effects; Escherichia coli/metabolism; Escherichia coli Proteins/metabolism; Lipoproteins/metabolism; Membrane Transport Proteins/metabolism; Microbial Sensitivity Tests; Multidrug Resistance-Associated Proteins/metabolism; Quinolones/metabolism; Quinolones/pharmacology; Serial Passage; Tetracycline/metabolism; Tetracycline/pharmacology; beta-Lactams/metabolism; beta-Lactams/pharmacology

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