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Transcriptional response of Streptococcus pneumoniae to Zn2+-limitation and the repressor/activator function of AdcR

ABSTRACT: Zinc (Zn2+) is an important trace metal ion that has been shown to regulate the expression of several (virulence) genes in streptococci. Previously, we analyzed the genome-wide response of S. pneumoniae to Zn2+-stress. In this work, we have performed a transcriptomic analysis to identify genes that are differentially expressed under intracellular Zn2+-limitation. This revealed a number of genes that are highly upregulated in the absence of extracellular Zn2+, amongst which the genes belonging to the regulon of the Zn2+-responsive repressor AdcR, like adcBCA, encoding a Zn2+-dependent ABC-uptake system, adcAII, encoding a Zn2+-binding lipoprotein, and also virulence genes belonging to the Pht family (phtA, phtB, phtD and phtE). Using transcriptome analysis, lacZ-reporter studies, in vitro DNA binding experiments, and in silico operator predictions, we show that AdcR directly represses the promoters of adcRCBA, adcAII-phtD, phtA, phtB and phtE in the presence of Zn2+. AdcR can also function as an activator, since in the presence of Zn2+ it directly induces expression of adh that encodes a Zn2+-containing alcohol dehydrogenase. In conclusion, the genome-wide transcriptional response of S. pneumoniae to Zn2+-limitation was established, which is mainly mediated via direct regulation by the Zn2+-dependent regulator AdcR. This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Streptococcus pneumoniae D39

PROVIDER: GSE29236 | GEO | 2011/05/13

SECONDARY ACCESSION(S): PRJNA139945

REPOSITORIES: GEO

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Transcriptional response of Streptococcus pneumoniae to Zn2+-limitation and the repressor/activator function of AdcR

Project description:Zinc (Zn2+) is an important trace metal ion that has been shown to regulate the expression of several (virulence) genes in streptococci. Previously, we analyzed the genome-wide response of S. pneumoniae to Zn2+-stress. In this work, we have performed a transcriptomic analysis to identify genes that are differentially expressed under intracellular Zn2+-limitation. This revealed a number of genes that are highly upregulated in the absence of extracellular Zn2+, amongst which the genes belonging to the regulon of the Zn2+-responsive repressor AdcR, like adcBCA, encoding a Zn2+-dependent ABC-uptake system, adcAII, encoding a Zn2+-binding lipoprotein, and also virulence genes belonging to the Pht family (phtA, phtB, phtD and phtE). Using transcriptome analysis, lacZ-reporter studies, in vitro DNA binding experiments, and in silico operator predictions, we show that AdcR directly represses the promoters of adcRCBA, adcAII-phtD, phtA, phtB and phtE in the presence of Zn2+. AdcR can also function as an activator, since in the presence of Zn2+ it directly induces expression of adh that encodes a Zn2+-containing alcohol dehydrogenase. In conclusion, the genome-wide transcriptional response of S. pneumoniae to Zn2+-limitation was established, which is mainly mediated via direct regulation by the Zn2+-dependent regulator AdcR. Two condition design comparison of Wild-type strain including a dye swap Refer to individual Series. This SuperSeries is composed of the following subset Series: GSE29234: adcR mutant vs wild type D39 GSE29235: Low Zn vs high Zn in CDM

2011-05-13 | E-GEOD-29236 | biostudies-arrayexpress

The regulation of the AdcR regulon in Streptococcus pneumoniae depends both on Zn2+- and Ni2+- availability

Project description:By using the transcriptomic approach, we have elucidated the effect of Ni2+ on the global gene expression of S. pneumoniae D39 by identifying several differentially expressed genes/operons in the presence of a high extracellular concentration of Ni2+. The genes belonging to the AdcR regulon (adcRCBA, adcAII-phtD, phtA, phtB and phtE) and the PsaR regulon (pcpA, prtA and psaBCA) were highly upregulated in the presence of Ni2+. We have further studied the role of Ni2+ in the regulation of the AdcR regulon by using ICP-MS analysis, electrophoretic mobility shift assays and transcriptional lacZ-reporter studies, and demonstrate that Ni2+ is directly involved in the derepression of the AdcR regulon via the Zn2+-dependent repressor AdcR, and has an opposite effect on the expression of the AdcR regulon as compared to Zn2+. This SuperSeries is composed of the SubSeries listed below.

2015-11-20 | GSE73852 | GEO

D39 wild-type vs D39 ÎadcR In CDM with 0.3 mM Ni2+

Project description:By using the transcriptomic approach, we have elucidated the effect of Ni2+ on the global gene expression of S. pneumoniae D39 by identifying several differentially expressed genes/operons in the presence of a high extracellular concentration of Ni2+. The genes belonging to the AdcR regulon (adcRCBA, adcAII-phtD, phtA, phtB and phtE) and the PsaR regulon (pcpA, prtA and psaBCA) were highly upregulated in the presence of Ni2+. We have further studied the role of Ni2+ in the regulation of the AdcR regulon by using ICP-MS analysis, electrophoretic mobility shift assays and transcriptional lacZ-reporter studies, and demonstrate that Ni2+ is directly involved in the derepression of the AdcR regulon via the Zn2+-dependent repressor AdcR, and has an opposite effect on the expression of the AdcR regulon as compared to Zn2+. Comparison of the Streptococcus pneumoniae D39 wild-type vs D39 ÎadcR in CDM Plus 0.3 mM Ni2+ Two condition design comparison of Wild-type strain vs mutant strain including a dye swap

2015-11-20 | E-GEOD-73851 | biostudies-arrayexpress

The metalloregulatory site in Streptococcus pneumoniae AdcR, a zinc-activated MarR-family repressor

2010-10-01 | GSE21506 | GEO

High Ni2+ vs Low Ni2+

Project description:By using the transcriptomic approach, we have elucidated the effect of Ni2+ on the global gene expression of S. pneumoniae D39 by identifying several differentially expressed genes/operons in the presence of a high extracellular concentration of Ni2+. The genes belonging to the AdcR regulon (adcRCBA, adcAII-phtD, phtA, phtB and phtE) and the PsaR regulon (pcpA, prtA and psaBCA) were highly upregulated in the presence of Ni2+. We have further studied the role of Ni2+ in the regulation of the AdcR regulon by using ICP-MS analysis, electrophoretic mobility shift assays and transcriptional lacZ-reporter studies, and demonstrate that Ni2+ is directly involved in the derepression of the AdcR regulon via the Zn2+-dependent repressor AdcR, and has an opposite effect on the expression of the AdcR regulon as compared to Zn2+. Comparison of the Streptococcus pneumoniae D39 wild-type in CDM Plus 0.5 mM Ni and CDM plus 0 mM Ni2+ Two condition design comparison of two conditions 0.5 mM Ni2+ Vs 0 mM Ni2+ including a dye swap

2015-11-20 | E-GEOD-73850 | biostudies-arrayexpress

The metalloregulatory site in Streptococcus pneumoniae AdcR, a zinc-activated MarR-family repressor

Project description:Streptococcus pneumoniae D39 AdcR (adhesion competence repressor) is the first metal-sensing member of the MarR (multiple antibiotic resistance repressor) family to be characterized. Expression profiling of a âadcR strain grown in liquid culture under microaerobic conditions revealed that transcript amounts for 13 genes were up-regulated relative to the wild-type strain, among them adcR, adcCBA, encoding a high affinity ABC uptake system for zinc, and genes encoding cell-surface zinc-binding pneumococcal histidine triad (pht) and adcII (lmb, laminin binding) proteins. Down-regulated transcripts included those encoding two putative zinc-containing alcohol dehydrogenases. Bacterial strains were grown exponentially in rich (BHI) media at 37C and an atmosphere of 5% CO2 to OD620~0.2, and were processed as described in the related Sample records. Samples were collected from three independent biological replicates and included one dye swap. Data were normalized using the Lowess (block) method without background subtraction. Changes in relative transcript amounts of positive or negative 2-fold with Bayesian P value of <0.001 were considered significant, and were included as supplementary material for the accompanying manuscript (The metalloregulatory site in Streptococcus pneumoniae AdcR, a zinc-activated MarR-family repressor; Reyes-Caballero, H. et al, manuscript in preparation).

2010-10-01 | E-GEOD-21506 | biostudies-arrayexpress

adcR mutant vs wild type D39

Project description:Comparison of the Streptococcus pneumoniae D39 adcR mutant vs D39 wild type in CDM plus 0.2mM Zn One condition design comparison of two strains including a dye swap

2011-05-13 | E-GEOD-29234 | biostudies-arrayexpress

The regulation of the AdcR regulon in Streptococcus pneumoniae depends both on Zn2+- and Ni2+- availability

Project description:The regulation of the AdcR regulon in Streptococcus pneumoniae depends both on Zn2+- and Ni2+- availability

| PRJNA298223 | ENA

Impact of adcR delation on the transcriptome of Streptococcus pneumoniae D39 in the presence of Zinc

Project description:Transcriptome comparison of the Streptococcus pneumoniae D39 ΔadcR to D39 wild-type grown in CDM plus 0.2mM Zn2+.

2011-05-13 | GSE29234 | GEO

Intracellular Zn2+ transients modulate global gene expression in dissociated rat hippocampal neurons

Project description:Zinc (Zn2+) is an integral component of many proteins and has been shown to act in a regulatory capacity in different mammalian systems, including as a neurotransmitter in neurons throughout the brain. While Zn2+ plays an important role in modulating neuronal potentiation and synaptic plasticity, little is known about the signaling mechanisms of this regulation. In dissociated rat hippocampal neuron cultures, we used fluorescent Zn2+ sensors to rigorously define resting Zn2+ levels and stimulation-dependent intracellular Zn2+ dynamics, and we performed RNA-Seq to characterize Zn2+-dependent transcriptional effects upon stimulation. We found that relatively small changes in cytosolic Zn2+ during stimulation altered expression levels of 931 genes, and these Zn2+ dynamics induced transcription of many genes implicated in neurite expansion and synaptic growth. Additionally, while we were unable to verify the presence of synaptic Zn2+ in these cultures, we did detect the synaptic vesicle Zn2+ transporter ZnT3 and found it to be substantially upregulated by cytosolic Zn2+ increases. These results provide the first global sequencing-based examination of Zn2+-dependent changes in transcription and identify genes that may mediate Zn2+-dependent processes and functions.

2019-07-01 | GSE126841 | GEO

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