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Journal of Bacteriology, February 2005, p. 1246-1253, Vol. 187, No. 4
0021-9193/05/$08.00+0     doi:10.1128/JB.187.4.1246-1253.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Mutations in PA2491 (mexS) Promote MexT-Dependent mexEF-oprN Expression and Multidrug Resistance in a Clinical Strain of Pseudomonas aeruginosa

Mara L. Sobel, Shadi Neshat, and Keith Poole*

Department of Microbiology and Immunology, Queen's University, Kingston, Ontario, Canada

Received 29 September 2004/ Accepted 11 November 2004

Disruption of the PA2491 gene in a mini-Tn5-tet insertion mutant of a clinical isolate of Pseudomonas aeruginosa increased expression of the mexEF-oprN multidrug efflux genes and decreased production of outer membrane protein OprD, concomitant with enhanced resistance to chloramphenicol, quinolones, and imipenem, which was reminiscent of previously described nfxC mutants. PA2491 encodes a probable oxidoreductase previously shown to be positively regulated by the MexT positive regulator of mexEF-oprN expression (T. Köhler, S. F. Epp, L. K. Curty, and J. C. Pechére, J. Bacteriol. 181:6300-6305, 1999). Spontaneous multidrug-resistant mutants of the P. aeruginosa clinical isolate hyperexpressing mexEF-oprN and showing reduced production of OprD were readily selected in vitro, and all of them were shown to carry mutations in PA2491, highlighting the probable significance of such mutations as determinants of MexEF-OprN-mediated multidrug resistance in vivo.


* Corresponding author. Mailing address: Department of Microbiology and Immunology, Queen's University, Kingston, Ontario, Canada K7L 3N6. Phone: (613) 533-6677. Fax: (613) 533-6796. E-mail: poolek{at}post.queensu.ca.


Journal of Bacteriology, February 2005, p. 1246-1253, Vol. 187, No. 4
0021-9193/05/$08.00+0     doi:10.1128/JB.187.4.1246-1253.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




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