Gene expression changes in Corynebacterium glutamicum at increased growth temperature in the absence of PPIase FkpA
Ontology highlight
ABSTRACT:
ORGANISM(S): Corynebacterium glutamicum Corynebacterium glutamicum ATCC 13032
PROVIDER: GSE65294 | GEO | 2015/09/08
SECONDARY ACCESSION(S): PRJNA273637
REPOSITORIES: GEO
Similar Datasets
Project description:Comparative transcriptome analyses revealed 69 genes exhibiting ?2-fold mRNA level changes in C. glutamicum DfkpA.Overall, 34 genes exhibited ?2-fold increased and 35 genes at least 0.5-fold decreased mRNA levels in JVO1 DfkpA. About half of these genes (32) encode for hypothetical/putative proteins. LdhA encoding L-lactate dehydrogenase exhibited by far the strongest increased mRNA level (8.5-fold) in the absence of FkpA. Determination of the respective specific LdhA activities revealed about 2-fold increased activity in JVO1 DfkpA (0.73 ± 0.05 U/mg) compared to the reference JVO1 (0.41 ± 0.02 U/mg). Notably, the two short gene lists include four genes encoding transcriptional regulators exhibiting increased mRNA levels (farR, lexA, divS, znr) and two exhibiting decreased mRNA levels (ramB, mmpLR) in the absence of FkpA under the conditions tested. The mRNA level of cysK was increased (2.05-fold) which is repressed by RamB whose mRNA level was decreased (0.27-fold). In contrast, the mRNA level of RamB-repressed ald was decreased (0.31-fold) and not increased. To identify the influence of PPIase FkpA on global gene expression, DNA microarray analyses were performed with a ?fkpA mutant compared to the reference C. glutamicum JVO1. For this purpose RNA was isolated from exponentially growing cells cultivated in CgXII minimal medium with 4% glucose at increased temperature (35°C) above growth optimum of C. glutamicum. Two biological replicates were performed with each representing an intra-array duplicate.
2015-09-08 | E-GEOD-65294 | biostudies-arrayexpress
Project description:Purpose: Free nitrous acid (FNA) has recently been demonstrated as an antimicrobial agent to a range of microorganisms. However, its antimicrobial mechanism is largely unknown. For this study Pseudomonas aeruginosa PAO1 was selected to gain a systematic understanding of the antimicrobial mechanism of FNA. Methods: PAO1 was grown under anaerobic denitrifying conditions and when FNA was added (0.1 mg-N/L) growth temporarily stopped. From cultures with and without added FNA, RNA was extracted and the abundance of gene transcripts was detected by sequencing. Transcripts exhibiting â¥2.5 or â¤-2.5 fold abundance change in the presence of FNA were designated as differentially expressed. Results:In response to FNA, 167 genes showed increased transcription while 424 exhibited deceased transcript levels. Respiration was likely inhibited as denitrification activity was severely decreased. Genes coding for enzymes of the tricarboxylic acid cycle were down regulated, while highly increased transcripts were detected for pyruvate fermentation, indicating a possible survival response to FNA. Moreover, genes coding ribosomal proteins had significantly decreased transcript levels, implicating that protein biosynthesis was severely inhibited by FNA. Whereas, genes encoding proteins functioning to preserve ribosome units under stressful conditions, were up-regulated during FNA exposure. Conclusion: In this study, we performed genome-wide high throughput RNA sequencing (RNA-Seq) analysis on PAO1 in the absence and presence of a bacteriostatic-level of FNA (0.1 mg N/L). By combining the global activated/suppressed gene profiles and detected physiological responses, we detected the microbial response to FNA exposure and revealed potential antimicrobial mechanisms of FNA on this prevalent opportunistic pathogen and environmentally relevant denitrifier. mRNA profiles of P. aeruginosa PAO1 towards FNA stress were generated by next generation sequencing in triplicate via Illumina 2000.
2016-04-06 | E-GEOD-73323 | biostudies-arrayexpress
Project description:Purpose: Free nitrous acid (FNA) has recently been demonstrated as an antimicrobial agent to a range of microorganisms. However, its antimicrobial mechanism is largely unknown. For this study Pseudomonas aeruginosa PAO1 was selected to gain a systematic understanding of the antimicrobial mechanism of FNA. Methods: PAO1 was grown under anaerobic denitrifying conditions and when FNA was added (0.1 mg-N/L) growth temporarily stopped. From cultures with and without added FNA, RNA was extracted and the abundance of gene transcripts was detected by sequencing. Transcripts exhibiting ≥2.5 or ≤-2.5 fold abundance change in the presence of FNA were designated as differentially expressed. Results:In response to FNA, 167 genes showed increased transcription while 424 exhibited deceased transcript levels. Respiration was likely inhibited as denitrification activity was severely decreased. Genes coding for enzymes of the tricarboxylic acid cycle were down regulated, while highly increased transcripts were detected for pyruvate fermentation, indicating a possible survival response to FNA. Moreover, genes coding ribosomal proteins had significantly decreased transcript levels, implicating that protein biosynthesis was severely inhibited by FNA. Whereas, genes encoding proteins functioning to preserve ribosome units under stressful conditions, were up-regulated during FNA exposure. Conclusion: In this study, we performed genome-wide high throughput RNA sequencing (RNA-Seq) analysis on PAO1 in the absence and presence of a bacteriostatic-level of FNA (0.1 mg N/L). By combining the global activated/suppressed gene profiles and detected physiological responses, we detected the microbial response to FNA exposure and revealed potential antimicrobial mechanisms of FNA on this prevalent opportunistic pathogen and environmentally relevant denitrifier.
2016-04-06 | GSE73323 | GEO
Project description:<p>The etiologies of primary immunodeficiencies often yield novel insights about the immune system. Although a genetic etiology has been suspected for patients with abnormally low CD4+ T cells in the absence of HIV infection or any known causes of lymphopenia, no genetic mutation has been described to date for any case of primary CD4 lymphopenia. In this study, we characterized a non-consanguineous family with two non-HIV infected boys exhibiting an inverted CD4 to CD8 T cell ratio and a history of recurrent chronic viral infections since birth. Consistent with a decreased thymic output of CD4+ T cells, the percentage of CD31+ cells in the CD4+ naive population of these patients was decreased. In addition, the activation of T cells was significantly impaired in the patient upon TCR stimulation. Given the mother's T cells show completely skewed X chromosome inactivation, we suspected that the nature of this disease is X-linked. We performed X-chromosome exon-capture targeted single-end Solexa sequencing on two brothers and the mother and found a 10 base pair deletion at an intron-exon junction of Magnesium Transporter 1 (MAGT1), a Mg<sup>2+</sup> specific transporter. We confirmed that this deletion leads to altered splicing, frameshift, early termination of the mRNA, and deficient protein expression in the lymphocytes of the two patients. Moreover, knockdown of this transporter in T cells isolated from healthy donors can recapitulate the observed T cell activation defect while its ectopic expression in the patients' lymphocytes can restore T cell stimulation. Our discovery highlights the significance of this transporter to T cell function.</p>
| phs000365 | dbGaP
Project description:Acetamide (CAS 60-35-5) is detected in common foods including milk, eggs, beef, and roasted coffee beans. Chronic rodent bioassays using high doses (≥1000 mg/kg/day) suggest acetamide is a group 2B possible human carcinogen due to the induction of liver tumors. Weight-of-evidence indicates acetamide is not genotoxic, and therefore a threshold response is expected. We used a toxicogenomics approach in Wistar rats gavaged daily for 7 and 28 days to determine the benchmark dose (BMD), and investigate its mode of action from differential gene expression. Two exposure experiements were carried out in succsession. An initial dose range finding experiment used male Wistar rats gavaged daily for 7 days at 0, 30, 100, 300 and 1000 mg/kd/day. A second experiment used both male and female Wistar rats exposed for 7 and 28 days to 0, 300,500,750,1000 and 1500 mg/kg/day. No treatment related changes in terminal body weight, clinical chemistry, or histopathology were observed at doses of 30, 100, or 300 mkd. At 1000 mkd, the dose reported to elicit carcinogenesis, liver weights decreased 1.3-fold with the presence of single cell necrosis, hepatocyte vacuolization, and increased mitotic activity consistent with a 4.2 fold increase in the cell proliferation index. Accordingly, plasma ALT and AST were increased 2.0- and 2.2-fold, respectively. RNA-Seq analysis identified 1 differentially expressed gene at 300 mkd, and 2,685 at 1000 mkd (|fold-change| ≥ 1.5 and FDR ≤ 0.05). Down-regulated genes were associated with lipid metabolism while up-regulated genes included cell signaling, immune response, and cell cycle functions. Collectively, these results revealed a no-observable adverse effect level (NOAEL) and no-observed-transcriptional effect level (NOTEL) at 300 mkd, warranting further investigation at doses between 300 and 1000 mkd to identify the benchmark dose (BMD). Functional enrichment indicates perturbation of cell cycle and lipid metabolism, though a more refined dose-response evaluation will be needed to demonstrate dose-dependent effects related to the MOA of acetamide. Funding by the Bill and Melinda Gates Foundation (OPP1142801).
2020-01-13 | GSE132815 | GEO
Project description:Thiazolidinediones increase tissue insulin sensitivity and are protective against worsening of nephropathy and hypertension in diabetes. Mechanisms underlying protection at the renal level likely involve a variety of unknown changes in gene expression. We examined kidney gene expression in obese and lean Zucker rats in response to rosiglitazone (Avandia®), a peroxisome proliferator activated receptor (gamma-subtype) agonist. Lean and obese Zucker rats were treated with either control chow or chow with added rosiglitazone (3 mg/kg�bw) for 12 weeks (n = 3/group). Total kidney mRNA expression was evaluated using the Affymetrix Rat Genome 230 2.0 GeneChip. 903 probe sets were significantly (P < 0.05) altered with at least 1.5-fold changes between groups. In untreated obese rats, 300 probe sets were increased and 244 decreased, relative to lean. Increased genes included the β-subunit of the epithelial sodium channel (ENaC), the thiazide-sensitive Na-Cl cotransporter, and aquaporin 3. Decreased genes included angiotensin converting enzyme, type 1 (ACE1). FatiGO analysis showed that the highest number of altered genes between lean and obese belonged to the categories: ion binding, hydrolase activity, and protein binding. RGZ increased expression of uncoupling protein 1 (UCP1), CD36, and fatty acid binding protein 4 (FAbp4) in both lean and obese rats. In obese rats, 33 genes were normalized by RGZ (no longer different from lean) including ACE1, fatty acid synthase (Fasn), and stearoyl-coenzyme A desaturase 2 (Scd2). Ingenuity Pathways System analysis of genes upregulated by RGZ in obese rats revealed two major nodes affected: PPAR-gamma and tumor necrosis factor alpha (TNF-alpha). Experiment Overall Design: Twelve male Zucker rats (6 Lean and 6 Obese) were used in the study. Three rats from each body type were fed either with control diet (ground chow diet) or control diet with rosiglitazone (3 mg/kg body weight). The rats were weighed weekly and fed diets and recieved water ad libitum for 12 weeks.
2008-04-06 | E-GEOD-7193 | biostudies-arrayexpress
Project description:: Prostate cancer (PCa) is the most commonly diagnosed genital cancer in men worldwide. Among patients who developed advanced PCa, 80% suffered from bone metastasis, with a sharp drop in the survival rate. Using quantitative global succinylome analysis, we characterized a significant increase of lysine 118 succinylation (K118su) of lactate dehydrogenase A (LDHA), which plays a role in increasing LDHA activity. As a substrate of SIRT5, LDHA-K118su significantly increased the migration and invasion of PCa cells and LDHA activity in PCa patients.
2023-06-21 | PXD022005 | Pride
Project description:Dyskeratosis congenita (DC) is an inherited multi-system disorder, characterized by oral leukoplakia, nail dystrophy, and abnormal skin pigmentation, as well as high rates of bone marrow failure, solid tumors, and other medical problems such as osteopenia. DC and telomere biology disorders (collectively referred to as TBD here) are caused by germline mutations in telomere biology genes leading to very short telomeres and limited proliferative potential of hematopoietic stem cells. We found that skeletal stem cells (SSCs) within the bone marrow stromal cell population (BMSCs, also known as bone marrow-derived mesenchymal stem cells), may contribute to the hematological phenotype. TBD-BMSCs exhibited reduced clonogenicity, reduced telomerase activity, spontaneous differentiation into adipocytes and fibrotic cells, and increased senescence in vitro. Upon in vivo transplantation into mice, TBD-BMSCs failed to form bone or support hematopoiesis, unlike normal BMSCs. TERC reduction (a TBD-associated gene) in normal BMSCs by siTERC-RNA recapitulated the TBD-BMSC phenotype by reducing proliferation and secondary colony forming efficiency, and by accelerating senescence in vitro. Microarray profiles of control and siTERC-BMSCs showed decreased hematopoietic factors at the mRNA level, and decreased secretion of factors at the protein level. These findings are consistent with defects in SSCs/BMSCs contributing to bone marrow failure in TBD. RNA (5 mg) isolated from N-BMSCs, siNC-BMSCs and siTERC-BMSCs 72hrs after transfection using an RNeasy Mini kit (Qiagen), was reverse transcribed and hybridized to an Affymetrix GeneChip Human Genome U133 Plus 2.0 array (LMT, NCI-Frederick). Three independent replicates for each experimental condition were carried out to control for intra-sample variation. Genes that were under/over-represented by >2-fold were analyzed using GeneSpring software. Signal intensity values were normalized using RMA (Robust Multi-array Analysis) summarization and baseline transformation to median of all samples was performed. Entities were filtered based on their signal intensity values. Hierarchical clustering was performed on filtered signal intensity (>20.0), non-averaged, fold change >2. A fold change analysis (>10-fold) was performed to generate a list of top genes under/over represented between the groups.
2014-12-09 | E-GEOD-64023 | biostudies-arrayexpress
Project description:We investigated an acute kidney injury (AKI) model in rats induced by cisplatin (Cp) administration. The cisplatin is widely used since its biochemical and histopathological characteristics are representative of drug-induced AKI in humans. Male Wistar rats were dosed once ip with 0, 1 and 3 mg/kg cisplatin. Tubular necorsis was observed histopathologically in all treated rats and war recovery on day 26. Gene expression profiling of the kidney cortex with microarrays 3, 5, 8, and 26 days after single administration of 3mg/kg Cp revealed a major profile pattern characterized by maximally increased and decreased mRNA levels on day 8, with clear changes already found 3 days after treatment for about half of the mRNAs. The mRNA expression pattern after administration of 1mg/kg Cp was overall similar, yet with a dose-dependent smaller fold-change. In summary we found 274 mRNAs showing significantly altered levels in the kidney of which 162 were increased and 112 decreased, respectively. Functional interpretation of the proteins encoded by these mRNAs revealed induction of a DNA damage response likely caused by the known molecular activity of Cp as DNA alkylating agent. Increased mRNAs associated with apoptosis (encoded by the corresponding genes like B-cell lymphoma 3-encoded protein, Bcl3; mouse double minute 2 homolog, Mdm2; p21/WAF1 also known as cyclin-dependent kinase inhibitor 1), cell cycle regulation (encoded by the corresponding genes like Cyclin-G1, Ccng1; B-cell translocation gene 2, Btg2) and stress response may have partly been induced by the DNA damage, but also by the kidney damage associated with Cp administration. Increased levels of mRNAs indicating regeneration (encoded by the corresponding genes like SPARC- related modular calcium-binding protein 2, Smoc2; Tenascin C, Tnc) and decreased levels of mRNAs coding for proteins related to kidney function, indicating dedifferentiation, are likely related to the observed kidney injury. Male Han Wistar rats (8 weeks old) were randomly grouped (n = 6) and dosed once i.p. with 0, 1 or 3 mg/kg body weight cis-diamminedichloroplatinum (II) (cisplatin; Sigma Aldrich, Germany) diluted in 0.9% saline. For histopathological examination of the kidney and for kidney RNA isolation animals were euthanized on days 3, 5, 8 and 26.
2016-08-23 | E-GEOD-85957 | biostudies-arrayexpress