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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptation, Biological
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Anti-Bacterial Agents / metabolism*
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Anti-Bacterial Agents / pharmacology*
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Drug Resistance, Multiple, Bacterial*
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Escherichia coli / drug effects*
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Escherichia coli / metabolism*
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Escherichia coli Proteins / metabolism*
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Lipoproteins / metabolism*
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Membrane Transport Proteins / metabolism*
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Microbial Sensitivity Tests
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Multidrug Resistance-Associated Proteins / metabolism*
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Quinolones / metabolism
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Quinolones / pharmacology
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Serial Passage
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Tetracycline / metabolism
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Tetracycline / pharmacology
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beta-Lactams / metabolism
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beta-Lactams / pharmacology
Substances
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AcrA protein, E coli
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AcrB protein, E coli
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Anti-Bacterial Agents
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Escherichia coli Proteins
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Lipoproteins
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Membrane Transport Proteins
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Multidrug Resistance-Associated Proteins
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Quinolones
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beta-Lactams
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Tetracycline