Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Stress profile elicited by trehalose-6-phosphate accumulation in Mycobacterium tuberculosis

ABSTRACT: The otsB2 gene encoding trehalose-6-phosphate phosphatase is essential for in vitro growth of Mycobacterium tuberculosis and required to establish an acute infection in mice. Essentiality of otsB2 is due to direct or indirect toxic effects associated with the substrate trehalose-6-phosphate that accumulates when OtsB2 gene expression is impaired. In order to gain insight into the molecular basis of trehalose-6-phosphate mediated toxic effects, whole genome transcriptome profiling was done using RNA-seq. A conditional otsB2 mutant of Mycobacterium tuberculosis was generated by inserting an anhydrotetracycline-inducible promoter cassette upstream of the otsB2 start codon,and the transcriptome profile of a fully induced mutant resembling the wildtype phenotype was compared to that of a partially silenced mutant under conditions where 30% residual growth relative to the fully induced mutant was observed.

ORGANISM(S): Mycobacterium tuberculosis

PROVIDER: GSE70291 | GEO | 2016/11/21

SECONDARY ACCESSION(S): PRJNA288174

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Transcriptome analysis of VapC21 overexpression and deletion in Mycobacterium tuberculosis.

Project description:We report the effects of VapC21 overexpression on Mycobacterium tuberculosis H37Rv strain. The total RNA was isolated from M. tuberculosis harboring either pTetR-int or pTetR-Int-vapC21 the expression was induced with 50 ng/ml anhydrotetracycline for 24 hrs. We report the effect of deletion VapC21 on the transciptional profile of Mycobacterium tuberculosis Erdman strain. For RNA-seq analysis, total RNA was isolated from mid-log phase culture of either parental or △vapC21 mutant strain.

2020-10-05 | GSE154320 | GEO

Transcriptome analysis of MazF6 overexpression in Mycobacterium tuberculosis

Project description:We report the effects of MazF6 overexpression on Mycobacterium tuberculosis H37Rv strain. The total RNA was isolated from M. tuberculosis harboring either pTetR-int or pTetR-Int-mazF6 the expression was induced with 50 ng/ml anhydrotetracycline for 24 hrs.

2022-04-01 | GSE182591 | GEO

Maltose-1-Phosphate Stress Stimulon in Mycobacterium tuberculosis

Project description:New chemotherapeutics are urgently required to control the tuberculosis pandemic fueled by the emergence of multidrug- and extensively-drug-resistant Mycobacterium tuberculosis strains and the bacterium`s catastrophic alliance with HIV. Here we describe a novel trehalose-to-Î±-glucan pathway in M. tuberculosis comprising four enzymatic steps mediated by TreS, Pep2, GlgB, and GlgE, identified as an essential maltosyltransferase capable of utilizing maltose 1-phosphate. Using traditional and chemical reverse genetics, we show that GlgE inactivation causes rapid death of M. tuberculosis in vitro and in mice, through self-poisoning by maltose 1-phosphate accumulation driven by a self-amplifying feedback loop promoting pleiotropic phosphosugar-induced stress responses. Moreover, this Î±-glucan pathway exhibited a synthetic lethal interaction with the glucosyltransferase Rv3032 involved in biosynthesis of specialized Î±-glucan derivatives. The unique combination of gene essentiality within a synthetic lethal pathway validates GlgE as a new class of drug targets, revealing novel synergistic mechanisms to induce death in M. tuberculosis. Transcriptional profiling was performed to characterize the lethality induced by maltose 1-phosphate accumulation. Triplicate 10 mL cultures of the conditional lethal Mtb mutant strain H37Rv Delta treS Delta glgE (pMV361::treS) and of the vector control strain H37Rv Delta treS Delta glgE (pMV361) were grown in liquid culture to log-phase in the presence of 5 mM validamycin A (VA) to suppress M1P formation. Subsequently, cells were washed to remove the inhibitor; after 48 h of starvation for VA cultures were harvested. Keywords: tuberculosis, trehalose, compound treatment design, genetic modification design, and stimulus or stress design Three biological replicates with one dye-flip

2010-05-14 | E-GEOD-18575 | biostudies-arrayexpress

Maltose-1-Phosphate Stress Stimulon in Mycobacterium tuberculosis

Project description:New chemotherapeutics are urgently required to control the tuberculosis pandemic fueled by the emergence of multidrug- and extensively-drug-resistant Mycobacterium tuberculosis strains and the bacterium`s catastrophic alliance with HIV. Here we describe a novel trehalose-to-α-glucan pathway in M. tuberculosis comprising four enzymatic steps mediated by TreS, Pep2, GlgB, and GlgE, identified as an essential maltosyltransferase capable of utilizing maltose 1-phosphate. Using traditional and chemical reverse genetics, we show that GlgE inactivation causes rapid death of M. tuberculosis in vitro and in mice, through self-poisoning by maltose 1-phosphate accumulation driven by a self-amplifying feedback loop promoting pleiotropic phosphosugar-induced stress responses. Moreover, this α-glucan pathway exhibited a synthetic lethal interaction with the glucosyltransferase Rv3032 involved in biosynthesis of specialized α-glucan derivatives. The unique combination of gene essentiality within a synthetic lethal pathway validates GlgE as a new class of drug targets, revealing novel synergistic mechanisms to induce death in M. tuberculosis. Transcriptional profiling was performed to characterize the lethality induced by maltose 1-phosphate accumulation. Triplicate 10 mL cultures of the conditional lethal Mtb mutant strain H37Rv Delta treS Delta glgE (pMV361::treS) and of the vector control strain H37Rv Delta treS Delta glgE (pMV361) were grown in liquid culture to log-phase in the presence of 5 mM validamycin A (VA) to suppress M1P formation. Subsequently, cells were washed to remove the inhibitor; after 48 h of starvation for VA cultures were harvested. Keywords: tuberculosis, trehalose, compound treatment design, genetic modification design, and stimulus or stress design

2010-02-24 | GSE18575 | GEO

Mycobacterium tuberculosis Requires Phosphate-Responsive Gene Regulation to Resist Host Immunity

Project description:Mycobacterium tuberculosis persists in the lungs of mammalian hosts despite inducing an immune response dominated by the macrophage-activating cytokine interferon-gamma (IFN-gamma). We identified the M. tuberculosis phosphate uptake system component PstA1 as a factor required to resist IFN-gamma dependent immunity. A ∆pstA1 mutant was fully virulent in IFN-gamma-/- mice but was attenuated in mice lacking the IFN-gamma-inducible nitric oxide synthase (NOS2). This phenotype suggests that ∆pstA1 bacteria are hypersensitive to an IFN-gamma-dependent immune mechanism(s) other than NOS2. In other species, the Pst system participates in phosphate-responsive gene regulation by interacting with a two-component signal transduction system. We identified genes that exhibited dysregulated expression in the ∆pstA1 mutant and showed that aberrant gene expression was dependent on the two-component system response regulator RegX3. Deletion of regX3 suppressed the replication and virulence defects of ∆pstA1 bacteria in NOS2-/- mice, suggesting that the ∆pstA1 mutant is attenuated, in part, due to aberrant RegX3-dependent gene expression. Our data imply that phosphate is an important signal controlling M. tuberculosis gene expression during replication in the lung. Aerobically growing logarithmic phase Wt or pstA1/regX3/pstA1regX3 mutant strains were grown in phosphate replete media and analyzed after several hours. Experiments were repeated in triplicate (pstA1 mutant) or quadruplicate (regX3/pstA1regX3 mutant).

2013-01-01 | E-GEOD-36998 | biostudies-arrayexpress

Mycobacterium tuberculosis Requires Phosphate-Responsive Gene Regulation to Resist Host Immunity

2013-01-01 | GSE36998 | GEO

Mycobacterium tuberculosis

Project description:Stress profile elicited by trehalose-6-phosphate accumulation in Mycobacterium tuberculosis

| PRJNA288174 | ENA

Mycobacterium tuberculosis Phosphate Uptake System Component PstA2 is Not Required for Gene Regulation or Virulence

Project description:The Mycobacterium tuberculosis genome encodes two complete high-affinity Pst phosphate-specific transporters. We previously demonstrated that a membrane-spanning component of one Pst system, PstA1, was essential both for M. tuberculosis virulence and for regulation of gene expression in response to external phosphate availability. To determine if the alternative Pst system is similarly required for virulence or gene regulation, we constructed a deletion of pstA2. Transcriptome analysis revealed that PstA2 is not required for regulation of gene expression in phosphate-replete growth conditions. PstA2 was also dispensable for replication and virulence of M. tuberculosis in a mouse aerosol infection model. However, a ∆pstA1∆pstA2 double mutant was attenuated in mice lacking the cytokine interferon-gamma, suggesting that M. tuberculosis requires high-affinity phosphate transport to survive phosphate limitation encountered in the host. Surprisingly, ∆pstA2 bacteria were more resistant to acid stress in vitro. This phenotype is intrinsic to the alternative Pst transporter since a ∆pstS1 mutant exhibited similar acid resistance. Our data indicate that the two M. tuberculosis Pst transporters have distinct physiological functions, with the PstA1 transporter being specifically involved in phosphate sensing and gene regulation while the PstA2 transporter influences survival in acidic conditions.

2016-06-29 | GSE83812 | GEO

Mycobacterium tuberculosis Phosphate Uptake System Component PstA2 is Not Required for Gene Regulation or Virulence

Project description:The Mycobacterium tuberculosis genome encodes two complete high-affinity Pst phosphate-specific transporters. We previously demonstrated that a membrane-spanning component of one Pst system, PstA1, was essential both for M. tuberculosis virulence and for regulation of gene expression in response to external phosphate availability. To determine if the alternative Pst system is similarly required for virulence or gene regulation, we constructed a deletion of pstA2. Transcriptome analysis revealed that PstA2 is not required for regulation of gene expression in phosphate-replete growth conditions. PstA2 was also dispensable for replication and virulence of M. tuberculosis in a mouse aerosol infection model. However, a âpstA1âpstA2 double mutant was attenuated in mice lacking the cytokine interferon-gamma, suggesting that M. tuberculosis requires high-affinity phosphate transport to survive phosphate limitation encountered in the host. Surprisingly, âpstA2 bacteria were more resistant to acid stress in vitro. This phenotype is intrinsic to the alternative Pst transporter since a âpstS1 mutant exhibited similar acid resistance. Our data indicate that the two M. tuberculosis Pst transporters have distinct physiological functions, with the PstA1 transporter being specifically involved in phosphate sensing and gene regulation while the PstA2 transporter influences survival in acidic conditions. Aerobically growing logarithmic phase Wt or pstA2 mutant or pstA1A2 double mutant strains were grown in phosphate replete media and analyzed after several hours. Experiments were repeated in triplicate.

2016-06-29 | E-GEOD-83812 | biostudies-arrayexpress

MntR(Rv2788): a transcriptional regulator that controls manganese homeostasis in Mycobacterium tuberculosis.

Project description:Transcriptional profiling of SirR and manganese regulated expression of genes in Mycobacterium tuberculosis strains comparing high manganese vs. low manganese in Rv (wild type Mycobacterium tuberculosis) and ST70 (mntR mutant strain of Mycobacterium tuberculosis)

2015-12-08 | GSE70812 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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