Mycobacterium tuberculosis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA120279 | ENA |
REPOSITORIES: ENA
Similar Datasets
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
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 Three biological replicates with one dye-flip
2010-05-14 | E-GEOD-18575 | biostudies-arrayexpress
Project description:Mycobacterium tuberculosis Persister Stimulon
| PRJNA340377 | ENA
Project description:Pellicle Stimulon in Mycobacterium tuberculosis
| PRJNA159721 | ENA
Project description:This SuperSeries is composed of the following subset Series: GSE36341: mRNA degradation in Mycobacterium tuberculosis under aerobic conditions GSE36342: mRNA degradation in Mycobacterium smegmatis under aerobic conditions GSE36343: mRNA degradation in Mycobacterium tuberculosis during cold and hypoxic stress GSE36344: mRNA degradation in Mycobacterium tuberculosis with DosR ectopically induced Refer to individual Series
2012-03-08 | E-GEOD-36345 | biostudies-arrayexpress
Project description:TCA1 Stimulon in Mycobacterium tuberculosis
| PRJNA179515 | ENA
Project description:These data represent the global gene expression profile of Mycobacterium tuberculosis after 24 hrs and 72 hrs of inorganic phosphate starvation. Differentially regulated genes appear to include those encoding proteins involved in adaptation to phosphate starvation, namely those involved in phosphate regulation and phosphate assimilation, as well as those involved in the stringent response.
2009-09-22 | GSE14840 | GEO
Project description:Vitamin C Stimulon in Mycobacterium tuberculosis
| PRJNA181017 | ENA
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
Project description: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.
2016-11-21 | GSE70291 | GEO