An AcrAB-mediated multidrug-resistant phenotype is maintained following restoration of wild-type activities by efflux pump genes and their regulators

A. Martins (1) , C. Iversen (2) , L. Rodrigues (1) , G. Spengler (1) , J. Ramos (1) , W.V. Kern (3) , I. Couto (1, 4) , M. Viveiros (1) , S. Fanning (2) , J.M. Pages , L. Amaral (1)

1 ULISBOA - Universidade de Lisboa = University of Lisbon
2 School of Agriculture
3 University Hospital
4 FCT NOVA - Faculdade de Ciências e Tecnologia = School of Science & Technology

In this study, we aimed to answer the question 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?' 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, β-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.

Mots clés: Overexpression; Efflux pumps; MDR phenotype

A. Martins, C. Iversen, L. Rodrigues, G. Spengler, J. Ramos, et al.. An AcrAB-mediated multidrug-resistant phenotype is maintained following restoration of wild-type activities by efflux pump genes and their regulators. International Journal of Antimicrobial Agents, 2009, 34 (6), pp.602. ⟨10.1016/j.ijantimicag.2009.06.029⟩. ⟨hal-00556355⟩