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. 2009 Dec;34(6):602-4. doi: 10.1016/j.ijantimicag.2009.06.029. Epub 2009 Sep 5.


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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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


  • AcrA protein, E coli
  • AcrB protein, E coli
  • Anti-Bacterial Agents
  • Escherichia coli Proteins
  • Lipoproteins
  • Membrane Transport Proteins
  • Multidrug Resistance-Associated Proteins
  • Quinolones
  • beta-Lactams
  • Tetracycline