title: Characterization of an LysR family protein, SmeR from Serratia marcescens S6, its effect on expression of the carbapenem-hydrolyzing beta-lactamase Sme-1, and comparison of this regulator with other beta-lactamase regulators.
abstract: Serratia marcescens S6 produces a chromosomally encoded carbapenem-hydrolyzing class A beta-lactamase, Sme-1 (T. Naas, L. Vandel, W. Sougakoff, D. M. Livermore, and P. Nordmann, Antimicrob. Agents Chemother. 38:1262-1270, 1994). Upstream from smeA we identified a second open reading frame (EMBL accession number Z30237). This encodes a 33.1-kDa protein, SmeR, which has a high degree of homology with NmcR, the LysR regulatory protein of the only other sequenced carbapenem-hydrolyzing class A beta-lactamase, NmcA from Enterobacter cloacae NOR-1. It is weakly related to AmpR of the chromosomal cephalosporinase regulatory systems described in E. cloacae, Yersinia enterocolitica, Citrobacter freundii, and Pseudomonas aeruginosa and is very weakly related to other LysR-type regulators of class A beta-lactamases. SmeR is a weakly positive regulator for Sme-1 expression in the absence of or in the presence of beta-lactam inducers. The -35 and -10 regions of smeR are in the opposite orientations and are face-to-face relative to the smeA promoter. SmeR acts similarly to NmcR and not as the AmpR regulators described for class C beta-lactamase systems. SmeR is a weak inducer in the absence or presence of beta-lactams. As was found for the AmpC-AmpR and NmcA-NmcR systems, a putative SmeR-binding site was present upstream from the beta-lactamase gene promoter regions. beta-Galactosidase activity from a smeR-lacZ translational fusion was expressed constitutively and decreased in the presence of SmeR from a coresident plasmid, suggesting that SmeR is autogeneously controlled. Finally, beta-lactams did not affect the expression of SmeR, which is the second regulator of a class A carbapenem-hydrolyzing beta-lactamase to be identified.
authors.affiliation: Abteilung Mikrobiologie, Biozentrum der Universität Basel, Switzerland.
authors.forename: T
authors.initials: T
authors.lastname: Naas
authors.forename: D M
authors.initials: DM
authors.lastname: Livermore
authors.forename: P
authors.initials: P
authors.lastname: Nordmann
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D001483:Base Sequence; D015780:Carbapenems / Q000378:metabolism*; D003001:Cloning, Molecular; D003470:Culture Media; D004269:DNA, Bacterial / Q000378:metabolism; D005798:Genes, Bacterial; D005809:Genes, Regulator; D008969:Molecular Sequence Data; D010957:Plasmids; D012706:Serratia marcescens / Q000201:enzymology / Q000378:metabolism*; D014157:Transcription Factors; D014158:Transcription, Genetic; D001616:beta-Galactosidase / Q000378:metabolism; D001618:beta-Lactamases / Q000096:biosynthesis* / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D015780:Carbapenems; D003470:Culture Media; D004269:DNA, Bacterial; C094220:SmeR protein, Serratia marcescens; D014157:Transcription Factors; D001616:beta-Galactosidase; C094219:beta-lactamase Sme-1; D001618:beta-Lactamases