SmeC, an outer membrane multidrug efflux protein of Stenotrophomonas maltophilia.
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, beta-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 beta-lactamase activity provided by a C-terminally truncated L2 enzyme, which was apparently responsible for the beta-lactam resistance of the SmeABC-hyperexpressing mutant. This represents the first report of coregulation of an efflux resistance determinant and a beta-lactamase.
Li
Xian-Zhi
XZ
Department of Microbiology and Immunology, Queen's University, Kingston, Ontario, Canada K7L 3N6.
Zhang
Li
L
Poole
Keith
K
D001425:Bacterial Outer Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001692:Biological Transport; D003001:Cloning, Molecular; D018432:Drug Resistance, Multiple / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D009876:Operon; D017422:Sequence Analysis, DNA; D020615:Stenotrophomonas maltophilia / Q000235:genetics* / Q000378:metabolism; D001618:beta-Lactamases / Q000378:metabolism
D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D001618:beta-Lactamases