title: CelR-mediated activation of the cellobiose-utilization gene cluster in Streptococcus pneumoniae.
abstract: The human pathogen Streptococcus pneumoniae harbours many genes encoding phosphotransferase systems and sugar ABC (ATP-binding cassette) transporters, including systems for the utilization of the β-glucoside sugar cellobiose. In this study, we show that the transcriptional regulator CelR, which has previously been found to be important for pneumococcal virulence, activates the expression of the cellobiose-utilization gene cluster (cel locus) of S. pneumoniae. Expression directed by the two promoters present in the cel locus was increased in the presence of cellobiose as sole carbon source in the medium, while expression decreased in the presence of glucose in the medium. Furthermore, we have predicted a 22 bp putative CelR regulatory site (5'-YTTTCCWTAWCAWTWAGGAAAA-3') in the promoters of celA and celB, and in silico analysis showed that it is highly conserved in other pathogenic streptococci as well. Promoter truncations of celA and celB, where the half or full CelR regulatory site was deleted, confirmed that the CelR-binding site in PcelA and PcelB is functional. Transcriptome studies with the celR mutant and in silico prediction of the CelR regulatory site in the entire D39 genome sequence show that the cel locus is the only cluster of genes under the direct control of CelR. Therefore, CelR is a regulator dedicated to the cellobiose-dependent transcriptional activation of the cel locus.
authors.affiliation: Department of Molecular Genetics, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 7, 9747 AG Groningen, The Netherlands.
authors.forename: Sulman
authors.initials: S
authors.lastname: Shafeeq
authors.affiliation: Department of Molecular Genetics, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 7, 9747 AG Groningen, The Netherlands.
authors.forename: Tomas G
authors.initials: TG
authors.lastname: Kloosterman
authors.affiliation: Department of Molecular Genetics, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 7, 9747 AG Groningen, The Netherlands.
authors.forename: Oscar P
authors.initials: OP
authors.lastname: Kuipers
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D002475:Cellobiose / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D008969:Molecular Sequence Data; D005810:Multigene Family; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013296:Streptococcus pneumoniae / Q000235:genetics* / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D001426:Bacterial Proteins; C119069:CelR protein, bacteria; D012097:Repressor Proteins; D002475:Cellobiose