Unknown,Transcriptomics,Genomics,Proteomics

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Regulation of glutamine and glutamate metabolism by GlnR and GlnA in Streptococcus pneumoniae

ABSTRACT: Several genes involved in nitrogen metabolism are known to contribute to the virulence of pathogenic bacteria. Here, we studied the function of the nitrogen regulatory protein GlnR in the Gram-positive human pathogen Streptococcus pneumoniae. We demonstrate that GlnR mediates transcriptional repression of genes involved in glutamine synthesis and uptake (glnA, glnPQ), glutamate synthesis (gdhA), and the gene encoding the pentose phosphate pathway enzyme Zwf, which forms an operon with glnPQ. Moreover, the expression of gdhA is also repressed by the pleiotropic regulator CodY. The GlnR-dependent regulation occurs through a conserved operator sequence and is responsive to the concentration of glutamate, glutamine and ammonium in the growth medium. By means of in vitro binding studies and transcriptional analyses we show that the regulatory function of GlnR is dependent on GlnA. Mutants of glnA and glnP displayed significantly reduced adhesion to Detroit 562 human pharyngeal epithelial cells, suggesting a role for these genes in the colonization of the host by S. pneumoniae. Thus, our results provide a thorough insight into the regulation of glutamine and glutamate metabolism of S. pneumoniae as mediated by both GlnR and GlnA. Each amplicon was spotted twice (technical replicates) on the DNA microarray. These replicates are indicated in the platforms and DNA microarray data by the addition of _rep1, _rep2, etc. The RNA for wild-type and mutant strains was isolated in 3 independent biological replicates which were hybridized in (partly dye-swap) to the 3 slides for glnA and 3 slides for glnR.

ORGANISM(S): Streptococcus pneumoniae

SUBMITTER: Oscar Kuipers

PROVIDER: E-GEOD-5088 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Regulation of glutamine and glutamate metabolism by GlnR and GlnA in Streptococcus pneumoniae.

Kloosterman Tomas G TG Hendriksen Wouter T WT Bijlsma Jetta J E JJ Bootsma Hester J HJ van Hijum Sacha A F T SA Kok Jan J Hermans Peter W M PW Kuipers Oscar P OP

The Journal of biological chemistry 20060620 35

Several genes involved in nitrogen metabolism are known to contribute to the virulence of pathogenic bacteria. Here, we studied the function of the nitrogen regulatory protein GlnR in the Gram-positive human pathogen Streptococcus pneumoniae. We demonstrate that GlnR mediates transcriptional repression of genes involved in glutamine synthesis and uptake (glnA and glnPQ), glutamate synthesis (gdhA), and the gene encoding the pentose phosphate pathway enzyme Zwf, which forms an operon with glnPQ. ...[more]

PMID: 16787930

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