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Antimicrobial Agents and Chemotherapy, February 2002, p. 333-343, Vol. 46, No. 2
0066-4804/01/$04.00+0     DOI: 10.1128/AAC.46.2.333-343.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

SmeC, an Outer Membrane Multidrug Efflux Protein of Stenotrophomonas maltophilia

Xian-Zhi Li, Li Zhang, and Keith Poole*

Department of Microbiology and Immunology, Queen’s University, Kingston, Ontario, Canada K7L 3N6

Received 25 April 2001/ Returned for modification 29 August 2001/ Accepted 26 October 2001

A homologue of the mexAB-oprM multidrug efflux operon of Pseudomonas aeruginosa, smeABC, was cloned from Stenotrophomonas maltophilia by using, as a probe, a PCR product amplified from this organism with primers based on the mexB sequence. The smeABC genes were hyperexpressed in a mutant strain displaying resistance to several antimicrobials, including aminoglycosides, ß-lactams, and fluoroquinolones. Deletions in smeC but not smeB compromised this resistance, suggesting that SmeC contributed to the multidrug resistance of the mutant as part of another, as-yet-unidentified multidrug efflux system. Consistent with SmeC functioning independently of SmeAB, a promoter activity was identified upstream of smeC. Upstream of the smeABC genes, a putative two-gene operon, smeSR, encoding homologues of bacterial two-component regulatory systems was identified. The cloned smeR gene activated expression of a smeA-lacZ fusion, indicating that SmeR positively regulates expression of the smeABC genes. Consistent with this, the multidrug resistance of the SmeABC-hyperexpressing mutant was compromised by deletion of smeR. Intriguingly, SmeC expression in S. maltophilia paralleled a ß-lactamase activity provided by a C-terminally truncated L2 enzyme, which was apparently responsible for the ß-lactam resistance of the SmeABC-hyperexpressing mutant. This represents the first report of coregulation of an efflux resistance determinant and a ß-lactamase.

* 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.

Antimicrobial Agents and Chemotherapy, February 2002, p. 333-343, Vol. 46, No. 2
0066-4804/01/$04.00+0     DOI: 10.1128/AAC.46.2.333-343.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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