Browse
Submit Data
Databases
API
Help

Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

16 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Time course RNA-seq of Mycobacterium tuberculosis exposed to nitric oxide.

ABSTRACT: Mycobacterium tuberculosis is an intracellular human pathogen with the ability to resist and adapt to many adverse conditions it encounters upon infection. Among these, overcoming the production of nitric oxide by macrophages could be key for M. tuberculosis success. We have challenged M. tuberculosis with a sub-lethal concentration of nitric oxide and followed the transcriptomic response through RNA-seq for 48 hours.

INSTRUMENT(S): Illumina HiSeq 2000

ORGANISM(S): Mycobacterium tuberculosis H37Rv

SUBMITTER: Teresa Cortes

PROVIDER: E-MTAB-5557 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Publications

Delayed effects of transcriptional responses in Mycobacterium tuberculosis exposed to nitric oxide suggest other mechanisms involved in survival.

Cortes Teresa T Schubert Olga T OT Banaei-Esfahani Amir A Collins Ben C BC Aebersold Ruedi R Young Douglas B DB

Scientific reports 20170815 1

Mycobacterium tuberculosis has succeeded as a human pathogen for tens of thousands of years thanks to its ability to resist and adapt to the adverse conditions it encounters upon infection. Bacterial adaptation to stress is commonly viewed in the context of transcriptional regulation, with the implicit expectation that an initial transcriptomic response is tightly coupled to an ensuing proteomic response. However, after challenging M. tuberculosis with nitric oxide we found that the rapid transc ...[more]

PMID: 28811595

Similar Datasets

BCG vaccine strains lack narK2 and narX induction and exhibit altered phenotypes during dormancy

Project description:Mycobacterium tuberculosis is the causative agent of tuberculosis, a disease that affects one-third of the world’s population. The sole extant vaccine for tuberculosis is the live attenuated Mycobacterium bovis bacille Calmette-Guerin (BCG). We examined 13 representative BCG strains from around the world to ascertain their ability to express DosR-regulated dormancy antigens. These are known to be recognized by T-cells of M. tuberculosis infected individuals, especially those harboring latent infections. Differences in expression of these antigens could be valuable for use as diagnostic markers to distinguish BCG vaccination from latent tuberculosis. We determined that all BCG strains were defective for induction of two dormancy genes, narK2 (Rv1737c) and narX (Rv1736c). NarK2 is known to be necessary for nitrate respiration during anaerobic dormancy. Analysis of the narK2/X promoter region revealed a base substitution mutation in all tested BCG strains and M. bovis in comparison to the M. tuberculosis sequence. We also show that nitrate reduction by BCG strains during dormancy was greatly reduced compared to M. tuberculosis and varied between tested strains. Several dormancy regulon transcriptional differences were also identified among the strains, as well as variation in their growth and survival. These findings demonstrate defects in DosR regulon expression during dormancy and phenotypic variation between commonly used BCG vaccine strains. 12 different BCG strains were examined as well as M. tuberculosis H37Rv and M. bovis. Two arrays per strain were analyzed, one with the addition of nitric oxide and the other utilizing hypoxia treatment, both conditions shown to induce expression of the dormancy regulon. The reference sample for each array was log phase M. tuberculosis H37Rv.

2008-05-03 | E-GEOD-11315 | biostudies-arrayexpress

Mycobacterium bovis transcriptional response to nitric oxide

Project description:We used microarray hybridization to analyze the expression pattern of M. bovis after exposure to nitric oxide. In M. tuberculosis, this treatment has been shown to induce a response similar to the hypoxic stress. Results showed the up-regulation of 51 genes belonging to the DosR regulon. The most remarkable difference with M. tuberculosis was the lack of expression of narX and narK2 in M. bovis, both genes related to survival during hypoxic stress. We further confirm this by qRT-PCR and also explore differential activity at promoter level. Four independent biological replicates were analyzed for each condition, and two dye-swap experiments were included.

2010-05-17 | E-GEOD-15164 | biostudies-arrayexpress

Transcription profiling of mouse embryonic stem cells (D3-pOCT-mESC) grown in low concentrations of nitric oxide

Project description:In order to identify the genes regulated in mouse embryonic stem cells by the effect of low concentrations of nitric oxide (NO), we analysed the transcriptome of cells treated with NO and compared it to those of cells cultured in the absence of leukemia inhibitory factor (LIF), and in the presence of LIF. We used the cell line D3-pOct4, which carries the enhanced Green Fluorescence Protein gene (eGFP) under the control of the Oct-4 promotor. This line is continuously maintained in the undifferentiated state in comparison with the wild type line in the presence of LIF. Experiment Overall Design: D3-pOct4 cells cultured in the presence of 1000 U/ml of LIF, in the absence of LIF, and in the absence of LIF with 2uM of diethylenetriamine nitric oxide adduct (DETA)/NO were grown for 7 days, maintaining the conditions of the treatment everyday. DETA-NO (Sigma) was used as donor of nitric oxide. RNA was extracted and analyzed by Bioanalyzer of Agilent. The cDNA microarray chip used was Mouse Genome 430_2.0 (Affymetrix) and the data were analyzed with GeneChip Operating System v1.4.0.036 using global scaling as the normalization method.

2008-10-26 | E-GEOD-13235 | biostudies-arrayexpress

Transcription profiling of human CD3-positive T cells from SLE and controls reveals activation of mTOR controls the loss of TCRI? in lupus T cells through HRES-1/Rab4-regulated lysosomal degradation

Project description:CD3-positive T cells were negatively isolated from 10 SLE patients and 9 healthy controls without SLE. All of the SLE samples and control samples were compared with one another to identify baseline differences in expression due to the disease. Next, T cell preparations from 4 of the control subjects were stimulated with either Nitric Oxide (NOC-18) 600 uM for 24hr or stimulated through CD3/CD28 for 24hr to determine which genes were responsive to these signaling mechanisms. Here, we show that activity of the mammalian target of rapamycin (mTOR), which is a sensor of the mitochondrial transmembrane potential, is increased in SLE T cells. Activation of mTOR was inducible by NO, a key trigger of MHP which in turn enhanced the expression of HRES-1/Rab4, a small GTPase that regulates recycling of surface receptors through early endosomes. Expression of HRES-1/Rab4 was increased in SLE T cells and, in accordance with its dominant impact on the endocytic recycling of CD4, it was inversely correlated with diminished CD4 expression. HRES-1/Rab4 over-expression was also inversely correlated with diminished TCRÎ¶ protein levels. Combined with follow up studies, these results suggest that activation of mTOR causes the loss of TCRÎ¶ in lupus T cells through HRES-1/Rab4-dependent lysosomal degradation. Experiment Overall Design: 10 replicate T cell samples from SLE (Lupus) patients Experiment Overall Design: 9 replicate T cell samples from healthy control (BC) subjects Experiment Overall Design: 4 replicate Nitric Oxide (NOC-18) stimulated T cell samples from 4 of the control subjects Experiment Overall Design: 4 replicate CD3/CD28 stimulated T cell samples from 4 of the control subjects

2009-02-28 | E-GEOD-13887 | biostudies-arrayexpress

Gene expression profile of human embryonic stem cells growth in low concentrations of nitric oxide

Project description:Identification of genes regulated in human embryonic stem cells by the effect of low concentrations of nitric oxide. The transcriptome of cells treated with NO were compared with that of cells cultured in abscense of LIF, and undifferentiated ES cells cultured in presence of LIF. The H181 hES cell line was used for the experiments. These data complement a previous study realized in mES cells under the same NO conditions . The aim of the work is to know how NO modify transcriptome of ES cells and how participate in the modulation of self renewal and differentiation. Passages between 72 and 74 of the H181 cell line were cultured on Matrigel-coated tissue culture plates in presence of 8ng/ml of bFGF for maintain them undifferentiated (control). For treatments, cells were cultured in the absence of bFGF to induce differentiation and treat cells with 2uM of DETA/NO. Cells were grown for 6 days mantaining the conditions of the treatment each 19 hours. Dietilentriamine-NO (DETA-NO) (Sigma) was used as donor of nitric oxide. Expression data of cells treated with NO in absence of bFGF were compared with cells cultured in absence of this, in order to observe how the treatment affects the transcriptome, and if there is some similarity with undifferentiated condition in presence of bFGF.

2012-03-20 | E-GEOD-36609 | biostudies-arrayexpress

Transcription profiling of human umbilical vein endothelial cells to identify targets of pharmacological histone deacetylase inhibition

Project description:We and others have previously reported the paradoxical downregulation of endothelial nitric oxide synthase (eNOS, NOS3) steady-state mRNA by pharmacological histone deacetylase (HDAC) inhibitors. This microarray experiment was designed to identify novel targets of an HDAC inhibitor (trichostatin A (TSA), 500 nM, 24h, Sigma) in primary human endothelial cells (human umbilical vein endothelial cells, HUVEC). Experiment Overall Design: HUVEC were isolated and cultured from three individuals (n=3, biological replicates). Paired samples were then treated with TSA (500nM, 24h, Sigma) or a vehicle-control. After sample preparation, hybridization to Affymetrix Human Genome Focus Arrays, image acquisition and the evaluation of several quality control metrics, summary expression measures were computed using the MAS5.0, RMA and GCRMA pre-processing strategies, respectively. The values were generated using the affy and gcrma packages of the Bioconductor Project.

2008-06-14 | E-GEOD-5856 | biostudies-arrayexpress

Expression data from fission yeast Schizosaccharomyces pombe under nitrosative stress

Project description:Nitric oxide being a versatile molecule inside biological systems, from being both a cell signaling molecule to a potent stress agent, has significant effect in the transcriptional response in fission yeast. We have used fission yeast microarrays to identify cellular targets of Nitric Oxide (NO) and to further understand the cellular mechanism of NO action. We report the change in the global gene expression profile response to NO in S. pombe cells S. pombe cells were treated with pure NO donor compond detaNONOate for 15 minutes at 30 degrees celcius for both the wild type and pap1 deleted strain, the cells were processed through RNA extraction and hybridization on Affymetrix microarrays. We included pap1 deleted strain of S. pombe alongside wild type strain as we earlier reported that pap1 is important to combat nitrosative stress, so pap1 might control the expression of several genes under nitrosative stress. Wild type control and treated samples as well as Mutant control and treated sets are included in 2 biological replicates for each.

2015-01-30 | E-GEOD-50899 | biostudies-arrayexpress

Nitric oxide exposure induces production of Rpf-dependent differentially culturable mycobacteria

Project description:Rationale: Tuberculosis has a devastating impact on global health by claiming nearly 1.4 million lives each year. During infection Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, produces heterogenous populations some of which don’t produce colonies on agar but grow in liquid media and often require supplementation with culture supernatants or recombinant Resuscitation-promoting factor, thus defined as differentially culturable bacilli. Objectives: to evaluate whether exposure to nitric oxide (NO), a well-known host defence molecule, alters mycobacterial growth phenotypes and drives generation of Rpf-dependent differentially culturable bacilli. Methods: a novel NO donor was synthesised and tested against Mtb and Mycobacterium bovis BCG in vitro, followed by growth assays, flow cytometry analysis and assessment of transcriptomic responses. Resuscitation-promoting factor (Rpf) inhibitors were used to characterise the role of Rpf proteins in the reactivation of NO-treated mycobacteria. Mycobacterial phenotypes were also investigated during infection of THP-1 macrophages activated with retinoic acid and vitamin D3. Measurements and Main Results: differentially culturable mycobacteria were generated after exposure to the novel NO donor or during infection of activated THP-1 cells. Resuscitation of these differentially culturable bacilli was largely abolished by specific Rpf inhibitors. Transcriptomic analysis revealed redox-associated stress signatures mediated by SigH and SigF, with significant down-regulation of ribosome and cell wall architecture genes, including rpfA, rpfB and rpfE, and induction of genes involved in response to thiol stress, sulphur metabolism and iron acquisition. Conclusion: Our study provides mechanistic insights into the generation of Rpf-dependent Mtb during tuberculosis and outlines a critical role of NO in this process.

2023-09-01 | E-MTAB-10776 | biostudies-arrayexpress

Characterization of RA839, a non-covalent small-molecule binder to Keap1 and selective activator of Nrf2 signalling

Project description:The activation of the transcription factor NF-E2-related factor 2 (Nrf2) maintains cellular homeostasis in response to oxidative stress by the regulation of multiple cytoprotective genes. Without stressors the activity of Nrf2 is inhibited by its interaction with the kelch-like ECH-associated protein 1 (Keap1). Here, we describe RA839, a small molecule that binds non-covalently to the Nrf2-interacting kelch domain of Keap1 with a Kd of approximately 6 µM, as demonstrated by X-ray co-crystallization and isothermal titration calorimetry. Whole-genome DNA arrays showed that at 10 µM RA839 significantly regulated 105 genes in bone marrow-derived macrophages. Canonical pathway mapping of these genes revealed an activation of pathways linked with Nrf2 signalling. These pathways were also activated after the activation of Nrf2 by the silencing of Keap1 expression. RA839 regulated only two genes in Nrf2 knockout macrophages. Similar to the activation of Nrf2 by either silencing of Keap1 expression or by the reactive compound CDDO-Me, RA839 prevented the induction of both inducible nitric oxide synthase expression and nitric oxide release in response to lipopolysaccharides in macrophages. In mice RA839 acutely induced Nrf2-target gene expression in liver. RA839 is a selective inhibitor of the Keap1/Nrf2 interaction and a useful tool compound to study the biology of Nrf2. Gene expression profile of bone marrow derived murine macrophages (BMDM) from Nrf2+/+ or Nrf2-/- mice treated with RA838, siKeap1-1 or siKeap1-2 were compared to untreated DMSO control or siControl. Four biological replicates were used for each sample group.

2015-10-31 | E-GEOD-71695 | biostudies-arrayexpress

PrrA modulates Mycobacterium tuberculosis response to nitric oxide

Project description:The purpose of this study was to understand the impact of prrA overexpression on global M. tuberculosis transcriptional response to nitric oxide.

2022-06-23 | GSE198997 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data