Mycobacterium tuberculosis Lsr2 ChIP-seq
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ABSTRACT:
PROVIDER: PRJEB31102 | ENA |
REPOSITORIES: ENA
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Project description:Two billion people are estimated to have latent tuberculosis infection associated with dormant Mycobacterium tuberculosis. Mycobacteria possess a great portfolio of regulatory proteins which that control transitions betweento dormancy and resuscitation, including the essential protein kinase B (PknB). Here, we established that depletion of PknB resulted in global alteration of the M. tuberculosis transcriptome, and identified and implicated the DNA-binding protein Lsr2 as a main transcriptional regulator likely responsible for these changes. Furthermore, we showed that Lsr2 was phosphorylated by PknB in vitro and phosphorylation of Lsr2 on threonine 112 was important for M. tuberculosis growth and survival in the Wayne non-replicating persistence model. Our fluorescence anisotropy and electromobility shift assays revealed demonstrated that phosphorylation prevented reduced affinity of Lsr2 binding to DNA, and ChHIP-sequencing experiments confirmed increased DNA binding by of a phosphoablative (T112A) Lsr2 mutant in M. tuberculosis. According to our structural modelling studies revealed that phosphomimetic T112D mutation (T112D) to Lsr2 resulted in increased dynamics of the C-terminal part and a shift of the DNA binding loop of in the Lsr2 DNA binding domain, which disrupted prevented the DNA-protein interactions. Our findings suggest that PknB- mediated phosphorylation of Lsr2 is necessary for fine- tuning of gene expression during M. tuberculosis growth and transition to dormancy enabling M. tuberculosis to adapt and survive to cause disease.
2019-10-02 | E-MTAB-7627 | biostudies-arrayexpress
Project description:To survive a dynamic host environment, Mycobacterium tuberculosis must endure a series of challenges from reactive oxygen and nitrogen stress, to drastic shifts in oxygen availability. The mycobacterial Lsr2 protein has been implicated in reactive oxygen defense via direct protection of DNA. To examine the role of Lsr2 in pathogenesis and physiology of M. tuberculosis, we generated a strain deleted for lsr2. Analysis of the M. tuberculosis ?lsr2 strain demonstrated that Lsr2 is not required for DNA protection, as this strain was as equally susceptible as the wild-type to DNA-damaging agents. The lsr2 mutant did display severe growth defects under normoxic and hyperoxic conditions, but was not required for growth under low oxygen conditions. However, it was also required for adaptation to anaerobiosis. The defect in anaerobic adaptation led to a marked decrease in viability during, as well as a lag in recovery from, anaerobiosis. Gene expression profiling of ?lsr2 under aerobic and anaerobic conditions in conjunction with published DNA binding-site data indicate that Lsr2 is a global transcriptional regulator controlling adaptation to changing oxygen levels. The ?lsr2 strain was capable of establishing an early infection in the Balb/c mouse model; however, it was severely defective in persisting in the lungs and caused no discernible lung pathology. These findings demonstrate M. tuberculosis Lsr2 is a global transcriptional regulator required for control of genes involved in adaptation to extremes in oxygen availability and is required for persistent infection. Wild type H37Rv or lsr2 mutant strains were grown aerobically or in a Rach dormancy model in dubos tween albumin media and analyzed. Alternately, either aerobically grown or Rach model hypoxic samples were challenged with H2O2 samples and harvested 1h later. Experiments were repeated in triplicate or quadruplicate.
2014-05-24 | E-GEOD-57948 | biostudies-arrayexpress
Project description:To survive a dynamic host environment, Mycobacterium tuberculosis must endure a series of challenges from reactive oxygen and nitrogen stress, to drastic shifts in oxygen availability. The mycobacterial Lsr2 protein has been implicated in reactive oxygen defense via direct protection of DNA. To examine the role of Lsr2 in pathogenesis and physiology of M. tuberculosis, we generated a strain deleted for lsr2. Analysis of the M. tuberculosis Δlsr2 strain demonstrated that Lsr2 is not required for DNA protection, as this strain was as equally susceptible as the wild-type to DNA-damaging agents. The lsr2 mutant did display severe growth defects under normoxic and hyperoxic conditions, but was not required for growth under low oxygen conditions. However, it was also required for adaptation to anaerobiosis. The defect in anaerobic adaptation led to a marked decrease in viability during, as well as a lag in recovery from, anaerobiosis. Gene expression profiling of Δlsr2 under aerobic and anaerobic conditions in conjunction with published DNA binding-site data indicate that Lsr2 is a global transcriptional regulator controlling adaptation to changing oxygen levels. The Δlsr2 strain was capable of establishing an early infection in the Balb/c mouse model; however, it was severely defective in persisting in the lungs and caused no discernible lung pathology. These findings demonstrate M. tuberculosis Lsr2 is a global transcriptional regulator required for control of genes involved in adaptation to extremes in oxygen availability and is required for persistent infection.
2014-05-24 | GSE57948 | GEO
Project description:Bacterial nucleoid-associated proteins play important roles in chromosome organization and global gene regulation. We find that Lsr2 of Mycobacterium tuberculosis is a novel nucleoid-associated protein that specifically binds AT-rich regions of the genome, including regions encoding major virulence factors, such as the ESX secretion systems, the lipid virulence factors PDIM/PGL, and the PE/PPE families of antigenic proteins. Comparison of genome-wide binding data with expression data indicates that Lsr2 binding results in transcriptional repression. Domain swamping experiments demonstrate that Lsr2 has an N-terminal dimerization domain and a C-terminal DNA binding domain. NMR analysis of the DNA binding domain of Lsr2 and its interaction with DNA reveals a novel structure and a unique mechanism that enables Lsr2 to discriminately target AT-rich sequences through interactions with the minor groove of DNA. Taken together, we provide evidence that mycobacteria have employed a structurally distinct molecule with an apparently different DNA recognition mechanism to achieve an equivalent function as the Enterobacteriaceae H-NS, coordinating global gene regulation and virulence in this group of medically important bacteria. Comparison of Lsr2 chromatin-immunoprecipitated DNA sequences to total reference DNA
2010-06-19 | E-GEOD-18652 | biostudies-arrayexpress
Project description:Bacterial nucleoid-associated proteins play important roles in chromosome organization and global gene regulation. We find that Lsr2 of Mycobacterium tuberculosis is a novel nucleoid-associated protein that specifically binds AT-rich regions of the genome, including regions encoding major virulence factors, such as the ESX secretion systems, the lipid virulence factors PDIM/PGL, and the PE/PPE families of antigenic proteins. Comparison of genome-wide binding data with expression data indicates that Lsr2 binding results in transcriptional repression. Domain swamping experiments demonstrate that Lsr2 has an N-terminal dimerization domain and a C-terminal DNA binding domain. NMR analysis of the DNA binding domain of Lsr2 and its interaction with DNA reveals a novel structure and a unique mechanism that enables Lsr2 to discriminately target AT-rich sequences through interactions with the minor groove of DNA. Taken together, we provide evidence that mycobacteria have employed a structurally distinct molecule with an apparently different DNA recognition mechanism to achieve an equivalent function as the Enterobacteriaceae H-NS, coordinating global gene regulation and virulence in this group of medically important bacteria.
2009-11-15 | GSE18652 | GEO
Project description:In the present study, we sought to explore the role of Lsr2 as a regulator of transcription in the saprophytic species, M. smegmatis. We used RNA-seq to compare the global transcription profiles of Δlsr2 and wild-type M. smegmatis strains in an attempt to decode Lsr2 regulatory network under optimal conditions or during hypoxia. We show that Lsr2 binds AT-rich regions and mainly acts as a gene repressor, either directly by binding promoter regions or indirectly through DNA-loop formation.
2021-04-22 | GSE169318 | GEO
Project description:In this study, we analyze the role of Lsr2 as a transcription factor in M. smegmatis, a saprophytic bacterium whose natural habitat (soil and water) substantially differs from that of the obligatory mycobacterial pathogens. In summary, the combined RNA-seq and ChIP-seq data revealed that Lsr2 controls gene expression either directly by binding their promoter regions or indirectly through DNA loop formation.
2021-04-22 | GSE164708 | GEO
Project description:The purpose of this study was to understand how prevention of serine/threonine protein kinase (STPK) phosphorylation of PrrA impacts PrrA modulation of M. tuberculosis transcriptional response to nitric oxide.
2022-06-23 | GSE198999 | GEO
Project description:The purpose of this study was to understand how prevention of serine/threonine protein kinase (STPK) phosphorylation of PrrA impacts PrrA modulation of M. tuberculosis transcriptional response to acidic pH and high chloride levels.
2022-06-23 | GSE199000 | GEO
Project description:Comparing gene expression of wild type and lsr2 mutants, to determine the effect of Lsr2 on Streptomyces development and metabolism
2018-06-09 | GSE115537 | GEO