Role of the Multidrug Efflux System MexXY in the Emergence of Moderate Resistance to Aminoglycosides among <i>Pseudomonas aeruginosa</i> Isolates from Patients with Cystic Fibrosis

  • Christelle Vogne
    Laboratoire de Bactériologie, Hôpital Jean Minjoz, F-25030 Besançon, France
  • Julio Ramos Aires
    Department of Molecular and Cell Biology, University of California, Berkeley, California 94720
  • Christiane Bailly
    Laboratoire de Bactériologie, Hôpital Jean Minjoz, F-25030 Besançon, France
  • Didier Hocquet
    Laboratoire de Bactériologie, Hôpital Jean Minjoz, F-25030 Besançon, France
  • Patrick Plésiat
    Laboratoire de Bactériologie, Hôpital Jean Minjoz, F-25030 Besançon, France

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<jats:title>ABSTRACT</jats:title> <jats:p> This study investigates the role of active efflux system MexXY in the emergence of aminoglycoside (AG) resistance among cystic fibrosis (CF) isolates of <jats:italic>Pseudomonas aeruginosa</jats:italic> . Three genotypically related susceptible and resistant (S/R) bacterial pairs and three other AG-resistant CF strains were compared to four non-CF strains moderately resistant to AGs. As demonstrated by immunoblot experiments, pump MexY was strongly overproduced in all of the resistant bacteria. This MexXY upregulation was associated with a 2- to 16-fold increase in the MICs of AGs in the S/R pairs and lower intracellular accumulation of dihydrostreptomycin. Alterations in <jats:italic>mexZ</jats:italic> , the repressor gene of operon <jats:italic>mexXY</jats:italic> , were found in all of the AG-resistant CF isolates and in one non-CF strain. Complementation of these bacteria with a plasmid-borne <jats:italic>mexZ</jats:italic> gene dramatically reduced the MICs of AGs, thus highlighting the role played by MexXY in the development of moderate resistance in CF patients. In contrast, complementation of the three non-CF strains showing wild-type <jats:italic>mexZ</jats:italic> genes left residual levels of resistance to AGs. These data indicate that a locus different from <jats:italic>mexZ</jats:italic> may be involved in overproduction of MexXY and that other nonenzymatic mechanisms contribute to AG resistance in <jats:italic>P. aeruginosa</jats:italic> . </jats:p>

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