Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

CelR-mediated activation of the cellobiose-utilization gene cluster in Streptococcus pneumoniae

ABSTRACT: Comparison of the Streptococcus pneumoniae D39 celR mutant compared to D39 wild type in M17 medium+ 0.5 % (w/v) Cellobiose (CM17) The human pathogen Streptococcus pneumoniae harbors many genes encoding phosphotransferase systems (PTSs) and sugar ABC (ATP-binding cassette) transporters, including systems for the utilization of the ?-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 a 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. One condition design comparision of two strains including a dye swap

ORGANISM(S): Streptococcus pneumoniae D39

SUBMITTER: Sulman Shafeeq

PROVIDER: E-GEOD-30891 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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CelR-mediated activation of the cellobiose-utilization gene cluster in Streptococcus pneumoniae.

Shafeeq Sulman S Kloosterman Tomas G TG Kuipers Oscar P OP

Microbiology (Reading, England) 20110721 Pt 10

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 promo ...[more]

PMID: 21778207

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Project description:Streptococcus pneumoniae is a strictly fermentative human pathogen that relies on carbohydrate metabolism to generate energy for growth. The nasopharynx colonised by the bacterium is poor in free sugars, but mucosa lining glycans can provide a source of sugar. In blood and inflamed tissues glucose is the prevailing sugar. As a result during progression from colonisation to disease S. pneumoniae has to cope with a pronounced shift in carbohydrate nature and availability. Thus, we set out to assess the pneumococcal response to sugars found in glycans and the influence of glucose (Glc) on this response at the transcriptional, physiological and metabolic levels. Galactose (Gal), N-acetylglucosamine (GlcNAc) and mannose (Man) affected the expression of 8 to 14% of the genes covering cellular functions including central carbon metabolism and virulence. The pattern of end-products as monitored by in vivo 13C-NMR is in good agreement with the fermentation profiles during growth, while the pools of phosphorylated metabolites are consistent with the type of fermentation observed (homolactic vs. mixed) and regulation at the metabolic level. Furthermore, the accumulation of -Gal6P and Man6P indicate metabolic bottlenecks in the metabolism of Gal and Man, respectively. Glc added to cells actively metabolizing other sugar(s)was readily consumed and elicited a metabolic shift towards a homolactic profile. The transcriptional response to Glc was large (over 5% of the genome). In central carbon metabolism (most represented category), Glc exerted mostly negative regulation. The smallest response was observed on a sugar mix, suggesting that exposure to varied sugars improves the fitness of S. pneumoniae. The expression of classical virulence factors was negatively controlled by Glc in a sugar-dependent manner. Overall, our results shed new light on the link between carbohydrate metabolism, adaptation to host niches and virulence. Two conditions with the same strain (D39), including a dye swap

Dataset Information

CelR-mediated activation of the cellobiose-utilization gene cluster in Streptococcus pneumoniae

Publications

CelR-mediated activation of the cellobiose-utilization gene cluster in Streptococcus pneumoniae.

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