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Mycobacterium tuberculosis Sensor Kinase DosS Modulates the Autophagosome in a DosR-independent Manner [II]

ABSTRACT: Transcriptional profiling of bacterial RNA samples from infected Rhesus Bone Marrow Derived Macrophages (RhBMDMs) compared to RNA isolated from respective in vitro grwon cultures viz M. tuberculosis H37Rv or Isogeneic mutant MtbdosS

ORGANISM(S): Mycobacterium tuberculosis Mycobacterium tuberculosis CDC1551 Mycobacterium tuberculosis H37Rv

PROVIDER: GSE118867 | GEO | 2018/08/22

REPOSITORIES: GEO

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Mycobacterium tuberculosis Sensor Kinase DosS Modulates the Autophagosome in a DosR-independent Manner [I]

Project description:Transcriptional profiling of RNA samples from un-infected Rhesus Bone Marrow Derived Macrophages (RhBMDMs) exposed to IMDM complete media used as control were compared to RNA from RhBMDMs infected for 24 hr with 'dos' mutants of Mtb viz. MtbΔdosR, MtbΔdosS, or MtbΔdosT

2018-08-22 | GSE118866 | GEO

Mycobacterium tuberculosis sensor kinase DosS modulates the autophagosome in a DosR-independent manner.

Project description:Dormancy is a key characteristic of the intracellular life-cycle of Mtb. The importance of sensor kinase DosS in mycobacteria are attributed in part to our current findings that DosS is required for both persistence and full virulence of Mtb. Here we show that DosS is also required for optimal replication in macrophages and involved in the suppression of TNF-? and autophagy pathways. Silencing of these pathways during the infection process restored full virulence in Mtb?dosS mutant. Notably, a mutant of the response regulator DosR did not exhibit the attenuation in macrophages, suggesting that DosS can function independently of DosR. We identified four DosS targets in Mtb genome; Rv0440, Rv2859c, Rv0994, and Rv0260c. These genes encode functions related to hypoxia adaptation, which are not directly controlled by DosR, e.g., protein recycling and chaperoning, biosynthesis of molybdenum cofactor and nitrogen metabolism. Our results strongly suggest a DosR-independent role for DosS in Mtb.

| S-EPMC6754383 | biostudies-literature

Mycobacterium tuberculosis Sensor Kinase DosS Modulates the Autophagosome in a DosR-independent Manner

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-08-22 | GSE118869 | GEO

The DosS-DosT/DosR Mycobacterial Sensor System.

Project description:DosS/DosR is a two-component regulatory system in which DosS, a heme-containing sensor also known as DevS, under certain conditions undergoes autophosphorylation and then transfers the phosphate to DosR, a DNA-binding protein that controls the entry of Mycobacterium tuberculosis and other mycobacteria into a latent, dormant state. DosT, a second sensor closely related to DosS, is present in M. tuberculosis and participates in the control of the dormancy response mediated by DosR. The binding of phosphorylated DosR to DNA initiates the expression of approximately fifty dormancy-linked genes. DosT is accepted to be a gas sensor that is activated in the ferrous state by the absence of an oxygen ligand or by the binding of NO or CO. DosS functions in a similar fashion as a gas sensor, but contradictory evidence has led to the suggestion that it also functions as a redox state sensor. This review focuses on the structure, biophysical properties, and function of the DosS/DosT heme sensors.

| S-EPMC4082495 | biostudies-literature

Mycobacterium tuberculosis Sensor Kinase DosS Modulates the Autophagosome in a DosR-independent Manner

Project description:Mycobacterium tuberculosis Sensor Kinase DosS Modulates the Autophagosome in a DosR-independent Manner

| PRJNA487069 | ENA

Mycobacterium tuberculosis Sensor Kinase DosS Modulates the Autophagosome in a DosR-independent Manner [II]

Project description:Mycobacterium tuberculosis Sensor Kinase DosS Modulates the Autophagosome in a DosR-independent Manner [II]

| PRJNA487075 | ENA

Mycobacterium tuberculosis Sensor Kinase DosS Modulates the Autophagosome in a DosR-independent Manner [I]

Project description:Mycobacterium tuberculosis Sensor Kinase DosS Modulates the Autophagosome in a DosR-independent Manner [I]

| PRJNA487072 | ENA

Phosphoproteomics of Mycobacterium tuberculosis DosR, DosS, and DosT

Project description:Mass Spectrometry based Phosphoproteomics was carried out on M. tuberculosis wild type strain H37Rv and the isogenic mutant strains MtbΔdosR, MtbΔdosS, and MtbΔdosT that were cultured in aerobic as well as hypoxic conditions. During later the oxygen was gradually deprived in cultures that were kept static.

2019-08-31 | PXD015256 | JPOST Repository

Unique roles of DosT and DosS in DosR regulon induction and Mycobacterium tuberculosis dormancy.

Project description:In Mycobacterium tuberculosis, the sensor kinases DosT and DosS activate the transcriptional regulator DosR, resulting in the induction of the DosR regulon, which is important for anaerobic survival and perhaps latent infection. The individual and collective roles of these sensors have been postulated biochemically, but their roles in vivo have remained unclear. This work demonstrates distinct and additive roles for each sensor during anaerobic dormancy. Both sensors are necessary for wild-type levels of DosR regulon induction, and concomitantly, full induction of the regulon is required for wild-type anaerobic survival. In the anaerobic model, DosT plays an early role, responding to hypoxia. DosT then induces the regulon and with it DosS, which sustains and further induces the regulon. DosT then loses its functionality as oxygen becomes limited, and DosS alone maintains induction of the genes from that point forward. Thus, M. tuberculosis has evolved a system whereby it responds to hypoxic conditions in a stepwise fashion as it enters an anaerobic state.

| S-EPMC2715697 | biostudies-literature

Mycobacterium tuberculosis Growth After Aerobic Expression of the DosR Regulon

Project description:Investigation of whole genome gene expression of M. tuberculosis strain H37Rv:deltaRv3133c::pEXNF-3133c following ectopic expression of a plasmid-borne copy of wildtype Rv3133c compared the same strain with Rv3133c uninduced. The M. tuberculosis H37Rv:deltaRv3133c was originally described in Mol Microbiol. 2003 May; 48(3): 833–843.

2012-01-31 | GSE33752 | GEO

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