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Antimicrobial Agents and Chemotherapy, April 2003, p. 1371-1375, Vol. 47, No. 4
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.4.1371-1375.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

MexXY-OprM Efflux Pump Is Necessary for Adaptive Resistance of Pseudomonas aeruginosa to Aminoglycosides

Laboratoire de Bactériologie, Hôpital Jean Minjoz, Besançon, France,¹ Department of Microbiology, Kyoto Pharmaceutical University, Kyoto, Japan,² Essential Therapeutics, Mountain View, California³

Received 26 February 2002/ Returned for modification 24 August 2002/ Accepted 23 January 2003

Exposure of Pseudomonas aeruginosa to aminoglycosides frequently selects for recalcitrant subpopulations exhibiting an unstable, "adaptive" resistance to these antibiotics. In this study, we investigated the implication in the phenomenon of MexXY-OprM, an active efflux system known to export aminoglycosides in P. aeruginosa. Immunoblotting experiments demonstrated that the transporter MexY, but not the outer membrane pore OprM, was overproduced during the post-drug exposure adaptation period in wild-type strain PAO1. Furthermore, MexY production was dependent upon the degree of bacterial exposure to gentamicin (drug concentration). In contrast to parental strain PAO1, mutants defective in MexXY or in OprM were unable to develop adaptive resistance. Altogether, these results indicate that the resistance process requires the rapid production of MexXY and the interaction of these proteins with the constitutively produced component OprM.

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