title: An AcrAB-mediated multidrug-resistant phenotype is maintained following restoration of wild-type activities by efflux pump genes and their regulators.
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.
authors.affiliation: Unit of Mycobacteriology, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisboa, Portugal.
authors.forename: A
authors.initials: A
authors.lastname: Martins
authors.forename: C
authors.initials: C
authors.lastname: Iversen
authors.forename: L
authors.initials: L
authors.lastname: Rodrigues
authors.forename: G
authors.initials: G
authors.lastname: Spengler
authors.forename: J
authors.initials: J
authors.lastname: Ramos
authors.forename: W V
authors.initials: WV
authors.lastname: Kern
authors.forename: I
authors.initials: I
authors.lastname: Couto
authors.forename: M
authors.initials: M
authors.lastname: Viveiros
authors.forename: S
authors.initials: S
authors.lastname: Fanning
authors.forename: J M
authors.initials: JM
authors.lastname: Pages
authors.forename: L
authors.initials: L
authors.lastname: Amaral
mesh_terms: D000220:Adaptation, Biological; D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial; D004926:Escherichia coli / Q000187:drug effects* / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D008074:Lipoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism*; D015363:Quinolones / Q000378:metabolism / Q000494:pharmacology; D012692:Serial Passage; D013752:Tetracycline / Q000378:metabolism / Q000494:pharmacology; D047090:beta-Lactams / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D029968:Escherichia coli Proteins; D008074:Lipoproteins; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015363:Quinolones; D013752:Tetracycline; D047090:beta-Lactams; C083497:AcrA protein, E coli; C083496:AcrB protein, E coli