Glutamate dehydrogenase (GdhA) of S. pneumoniae is required for high temperature adaptation
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ABSTRACT:
PROVIDER: PRJNA647689 | ENA |
REPOSITORIES: ENA
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Project description:During its progression from nasopharynx to other sterile and non-sterile niches of its human host, Streptococcus pneumoniae must cope with changes in temperature. We hypothesized that the pneumococcal temperature adaptation is an important facet of pneumococcal in host survival. Here we evaluate the effect of temperature on the phenotype of pneumococcus and the role of glutamate dehydrogenase (GdhA) during thermal stress adaptation associated with virulence and survival. Microarray analysis revealed a significant transcriptional response to temperature changes, affecting the expression of 132 and 119 genes at 34°C and 40°C, respectively, at mid-exponential growth phase relative to at 37ºC. One of the differentially regulated genes was gdhA, which is upregulated at 40°C while downregulated at 34°C relative to 37°C. Mutation of gdhA attenuated the growth, cell size, biofilm formation, pH survival, and virulence factor generation in a temperature dependent manner. Moreover, we identify that both D39 and ΔgdhA strains showed homo-lactic fermentation in glucose, however, ΔgdhA had higher formate production than D39 at all temperatures, which raised the hypothesis that gdhA involves in the regulation of pyruvate formate lyase (pflB) which is activated by catabolite control protein A (CcpA). In silico analysis pointed that a putative CcpA binding site (cre) was found in two proximal regions of -gdhA-coding sequence. The CcpA binding to the putative promoter region of gdhA was confirmed by EMSA. Furthermore, the transcriptional regulation of gdhA by CcpA, was temperature dependent. Finally, ΔgdhA grown at 34°C or 40°C was less virulent in Galleria mellonella infection model, suggesting that GdhA is required for pneumococcal virulence in fluctuating temperatures. These data demonstrated that temperature is an important parameter that affects physiology of S. pneumoniae and GdhA plays a significant role in temperature adaptation.
2021-11-24 | GSE154888 | GEO
Project description:Glud1 (glutamate dehydrogenase 1) transgenic mice release more excitatory neurotransmitter glutamate to synaptic cleft throughout lifespan and show signs of accelerated aging. Here we compared transcriptomic profiles of these animals to their wild-type counterparts. The hippocampus was used for the analysis. Keywords: transgenic analysis Three Glud1 transgenic mice vs. three age-matched wide-type mice. Age: 9-month-old. Tissue: hippocampus.
2010-07-12 | E-GEOD-11419 | biostudies-arrayexpress
Project description:Glud1 (glutamate dehydrogenase 1) transgenic mice release more excitatory neurotransmitter glutamate to synaptic cleft throughout lifespan and show signs of accelerated aging. Here we compared transcriptomic profiles of these animals to their wild-type counterparts. The hippocampus was used for the analysis. Keywords: transgenic analysis
2010-07-12 | GSE11419 | GEO
Project description:Glud1 (Glutamate dehydrogenase 1) transgenic mice release more excitatory neurotransmitter glutamate to synaptic cleft throughout lifespan. Here we compared transcriptomic profiles of these animals to their wild-type counterparts across 5 ages. The hippocampus was used for the analysis.
2014-07-31 | GSE48911 | GEO
Project description:Glud1 (Glutamate dehydrogenase 1) transgenic mice release more excitatory neurotransmitter glutamate to synaptic cleft throughout lifespan. Here we compared transcriptomic profiles of these animals to their wild-type counterparts across 5 ages. The hippocampus was used for the analysis. Longitudinal studies of Glud1 transgenic and wide-type mice across 5 age points: 10 days post birth, 4.5 mo, 9 mo, 14.5 mo, and 20 mo.
2014-07-31 | E-GEOD-48911 | biostudies-arrayexpress
Project description:During its progression from the nasopharynx to other sterile and nonsterile niches of its human host, Streptococcus pneumoniae must cope with changes in temperature. We hypothesized that the temperature adaptation is an important facet of pneumococcal survival in the host. Here, we evaluated the effect of temperature on pneumococcus and studied the role of glutamate dehydrogenase (GdhA) in thermal adaptation associated with virulence and survival. Microarray analysis revealed a significant transcriptional response to changes in temperature, affecting the expression of 252 genes in total at 34°C and 40°C relative to at 37°C. One of the differentially regulated genes was gdhA, which is upregulated at 40°C and downregulated at 34°C relative to 37°C. Deletion of gdhA attenuated the growth, cell size, biofilm formation, pH survival, and biosynthesis of proteins associated with virulence in a temperature-dependent manner. Moreover, deletion of gdhA stimulated formate production irrespective of temperature fluctuation. Finally, ΔgdhA grown at 40°C was less virulent than other temperatures or the wild type at the same temperature in a Galleria mellonella infection model, suggesting that GdhA is required for pneumococcal virulence at elevated temperature.
| S-EPMC8594611 | biostudies-literature
Project description:<p>Tet3 is the main α-ketoglutarate (αKG)-dependent dioxygenase in neurons that converts 5-methyl-dC into 5-hydroxymethyl-dC and further on to 5-formyl- and 5-carboxy-dC. Neurons possess high levels of 5-hydroxymethyl-dC that further increase during neural activity to establish transcriptional plasticity required for learning and memory functions. How αKG, which is mainly generated in mitochondria as an intermediate of the tricarboxylic acid cycle, is made available in the nucleus has remained an unresolved question in the connection between metabolism and epigenetics. We show that in neurons the mitochondrial enzyme glutamate dehydrogenase, which converts glutamate into αKG in an NAD+-dependent manner, is redirected to the nucleus by the αKG-consumer protein Tet3, suggesting on-site production of αKG. Further, glutamate dehydrogenase has a stimulatory effect on Tet3 demethylation activity in neurons, and neuronal activation increases the levels of αKG. Overall, the glutamate dehydrogenase-Tet3 interaction might have a role in epigenetic changes during neural plasticity.</p><p><br></p>
2021-06-24 | MTBLS2852 | MetaboLights
Project description:In this study, we performed a global quantitative proteomic analysis under extreme temperatures, pH, hydrostatic pressure (HP) and salinity on an archaeal strain, Thermococcus eurythermalis A501. Here is the result of temperature adaptation: low temperature (65°C) and high temperature (95°C), and the optimal culture condition (85°C, pH 7, 2.3% NaCl, 0.1 MPa or 10 MPa) was used as the control.
2020-09-09 | PXD018991 | Pride
Project description:Long term adaptation to enhanced temperature in Microcystis aeruginosa
| PRJEB58140 | ENA
Project description:Tet3 is an Fe2+-dependent enzyme that oxidizes genomic 5-methylcytosine to 5-hydroxymethylcytosine with the help of alpha-ketoglutarate and oxygen. It is the most abundant Tet enzyme in differentiated tissues including brain. Adult brain contains the highest 5-hydroxymethylcytosine levels. How alpha-ketoglutarate is made available for the oxidation of mC in brain cells and how the Tet activity is linked to neural activity are unsolved questions. Our experiments with full mouse brains show that Tet3 interacts in the nucleus directly with selected enzymes of the mitochondrial citric acid cycle. This leads to the formation of isocitrate. Tet3 also interacts with aspartate aminotransferase, which produces oxaloacetate. Although oxaloacetate and isocitrate are biosynthetic alpha-ketoglutarate precursors, they function as inhibitors of Tet3 and are needed to protect the reactive Fe2+ center from degrading DNA. The supply of Tet3 with alpha-ketoglutarate is established by a direct interaction of Tet3 with glutamate dehydrogenase (Glud1), which converts the neurotransmitter glutamate directly into alpha-ketoglutarate. This links Tet3 function to neural activity.
2021-05-10 | PXD004518 | Pride