An AcrAB-mediated multidrug-resistant phenotype is maintained following restoration of wild-type activities by efflux pump genes and their regulators.
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.
Martins
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A
Unit of Mycobacteriology, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisboa, Portugal.
Iversen
C
C
Rodrigues
L
L
Spengler
G
G
Ramos
J
J
Kern
W V
WV
Couto
I
I
Viveiros
M
M
Fanning
S
S
Pages
J M
JM
Amaral
L
L
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
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