SmeC, an Outer Membrane Multidrug Efflux Protein of Stenotrophomonas maltophilia

• DOI: 10.1128/aac.46.2.333-343.2002
• Publication Date: 2002-07-27T10:06:42Z
• Authors: Xian-Zhi Li; Li Zhang; Keith Poole
• Keywords: 0301 basic medicine; Stenotrophomonas maltophilia; Biological Transport; Gene Expression Regulation, Bacterial; Sequence Analysis, DNA; Drug Resistance, Multiple; beta-Lactamases; 03 medical and health sciences; Bacterial Proteins; Operon; Cloning, Molecular; Bacterial Outer Membrane Proteins

ABSTRACT

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, β-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 β-lactamase activity provided by a C-terminally truncated L2 enzyme, which was apparently responsible for the β-lactam resistance of the SmeABC-hyperexpressing mutant. This represents the first report of coregulation of an efflux resistance determinant and a β-lactamase.