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Journal of Bacteriology, August 2005, p. 5341-5346, Vol. 187, No. 15
0021-9193/05/$08.00+0     doi:10.1128/JB.187.15.5341-5346.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Induction of the MexXY Efflux Pump in Pseudomonas aeruginosa Is Dependent on Drug-Ribosome Interaction

Katy Jeannot,1 Mara L. Sobel,2 Farid El Garch,1 Keith Poole,2 and Patrick Plésiat1*

Laboratoire de Bactériologie, Hôpital J. Minjoz, F-25030 Besançon, France,1 Department of Microbiology and Immunology, Queen's University, Kingston, Ontario K7L 3N6, Canada2

Received 1 April 2005/ Accepted 12 May 2005

MexXY is an inducible efflux system that contributes to the natural resistance of Pseudomonas aeruginosa to antibiotics. Experiments involving real-time PCR after reverse transcription in reference strain PAO1 showed concentration-dependent induction of gene mexY by various ribosome inhibitors (e.g., chloramphenicol, tetracycline, macrolides, and aminoglycosides) but not by antibiotics acting on other cellular targets (e.g., ß-lactams, fluoroquinolones). Confirming a functional link between the efflux system and the translational machinery, ribosome protection by plasmid-encoded proteins TetO and ErmBP increased the resistance of a {Delta}mexAB-oprM mutant of PAO1 to tetracycline and erythromycin, respectively, as well as the concentrations of both drugs required to induce mexY. Furthermore, spontaneous mutations resulting in specific resistance to dihydrostreptomycin or spectinomycin also raised the minimal drug concentration for mexXY induction in strain PAO1. While strongly upregulated in a PAO1 mutant defective in gene mexZ (which codes for a putative repressor of operon mexXY), gene mexY remained inducible by agents such as tetracycline, chloramphenicol, and spectinomycin, suggesting additional regulatory loci for mexXY. Altogether, these data demonstrate physiological interplays between MexXY and the ribosome and are suggestive of an alternative function for MexXY beyond antibiotic efflux.

* Corresponding author. Mailing address: Laboratoire de Bactériologie, Hôpital Jean Minjoz, 25030 Besançon Cedex, France. Phone: (33) 3 81 66 82 86. Fax: (33) 3 81 66 89 14. E-mail: patrick.plesiat{at}univ-fcomte.fr.

Journal of Bacteriology, August 2005, p. 5341-5346, Vol. 187, No. 15
0021-9193/05/$08.00+0     doi:10.1128/JB.187.15.5341-5346.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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