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Impact of impaired polyamine biosynthesis on Streptococcus pneumoniae TIGR4 gene expression

ABSTRACT: Impact of impaired polyamine biosynthesis on Streptococcus pneumoniae TIGR4 gene expression

PROVIDER: PRJEB22705 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR2131460.fastq.gz	Fastqsanger.gz
	ERR2131461.fastq.gz	Fastqsanger.gz
	ERR2131462.fastq.gz	Fastqsanger.gz
	ERR2131463.fastq.gz	Fastqsanger.gz
	ERR2131464.fastq.gz	Fastqsanger.gz

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Impact of impaired polyamine biosynthesis on Streptococcus pneumoniae TIGR4 gene expression

Project description:The polyamine biosynthesis gene, speE, in Streptococcus pneumoniae TIGR4 is necessary for survival in murine models of pneumococcal pneumonia. To date, there is no description of polyamine biosynthesis dependent pneumococcal gene expression. In this study, we compared gene expression between the wild-type and biosynthesis deficient (speE) TIGR4 by RNA-Seq analysis.

2023-01-01 | E-MTAB-6070 | biostudies-arrayexpress

Polyamine synthesis effects capsule expression in Streptococcus pneumoniae TIGR4

Project description:Purpose: We recently reported that isogenic deletion of lysine decarboxylase (ΔcadA/SP_0916), an enzyme that catalyzes the biosynthesis of polyamine cadaverine in Streptococcus pneumoniae TIGR4 results in loss of capsular polysaccharide (CPS), which constitutes a novel mechanism of regulation of CPS. Here, we conducted RNA-Seq to elucidate molecular mechanisms of CPS regulation in polyamine synthesis impaired pneumococci. Result: Significantly differentially expressed genes in ΔcadA represent pneumococcal pathways involved in the biosynthesis of precursors for CPS and peptidoglycan. Conclusion: We establish a possible link and interchange between two cellular processes such as high energy demanding capsule production and oxidative stress responses in polyamine synthesis impaired pneumococci (ΔcadA).

2019-09-30 | GSE130511 | GEO

Polyamine biosynthesis in Salmonella

Project description:Verification of the polyamine biosynthesis mutant

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Polyamine synthesis effects capsule expression in Streptococcus pneumoniae TIGR4

Project description:Polyamine synthesis effects capsule expression in Streptococcus pneumoniae TIGR4

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RNA-seq analysis of transport deficient S. pneumoniae TIGR4 mutants

Project description:The polyamine transport operon in Streptococcus pneumoniae TIGR4 is necessary for survival in murine models of pneumococcal pneumonia. To date, there is no description of polyamine transport dependent pneumococcal gene expression. In this study, we compared gene expression between the wild-type and transport deficient (potABCD) TIGR4 by RNA-Seq analysis.

2017-08-14 | E-MTAB-5951 | biostudies-arrayexpress

Host response to S. pneumoniae TIGR4 and ΔpotABCD

Project description:The aim of this experiment is to determine the difference in protein expression, if any, in a mouse model of pneumococcal pneumonia using wild type and a polyamine transport operon deletion mutant strain of S. pneumoniae TIGR4, using expression proteomics. Eight week old female C57bl/6 mice were used in this study. The experimental design had two groups of 3 animals each that were administered 50 µL 1 X 107 CFU wild type S. pneumoniae TIGR4 or S. pneumoniae TIGR4 ΔpotABCD strain by intranasal instillation. The control group with three animals received 50 µL PBS. Mice were euthanized 4 hr and 12 hr post infection and lung tissues were harvested. The control group animals were euthanized 12 hr post infection.

2018-10-27 | PXD002300 | Pride

Inhibition of the Aryl Hydrocarbon Receptor - Polyamine Biosynthesis Axis Suppresses Multiple Myeloma and prostate cancer progression

Project description:Polyamine inhibition for cancer therapy is, conceptually, an attractive approach but has yet to meet success in the clinical setting. The aryl hydrocarbon receptor (AHR) is the central transcriptional regulator of xenobiotic response. Our study revealed that AHR also positively regulated intracellular polyamine production via direct transcriptional activation of two genes (ODC1 and AZIN1) involved in polyamine biosynthesis and control, respectively. In multiple myeloma patients, AHR levels inversely correlated with survival, suggesting that AHR inhibition may be beneficial for treatment of this disease .We identified clofazimine, an FDA-approved anti-leprosy drug, as a potent AHR antagonist and a suppressor of polyamine biosynthesis. Experiments in a transgenic model of multiple myeloma (Vk*Myc mice) and in immunocompromised mice bearing multiple myeloma cell xenografts, revealed high efficacy of clofazimine comparable to that of bortezomib, a first-in-class proteasome inhibitor used for treatment of multiple myeloma. This study identified a previously unrecognized regulatory axis between AHR and polyamine metabolism and discovered clofazimine as an inhibitor of AHR and a potentially clinically-relevant anti-multiple myeloma agent. RNA-seq: human multiple myeloma MM1S and human normal fibroblasts WI38 cells -/+ CLF 2-4uM for 24hrs; -/+ shAHR

2018-07-18 | GSE117160 | GEO

Polyamine and EIF5A hypusination downstream of c-Myc confers targeted therapy resistance in BRAF mutant melanoma

Project description:BRAF inhibitors are widely employed in the treatment of melanoma with the BRAF V600E mutation. However, the development of resistance greatly compromises their therapeutic efficacy. Here, we elucidate the role of polyamine biosynthesis and its regulatory mechanisms in promoting BRAF inhibitor resistance. Leveraging CRISPR-Cas9 screens, we identify AMD1 (S-adenosylmethionine decarboxylase 1), a critical enzyme for polyamine biosynthesis, as a druggable target whose inhibition reverses vemurafenib resistance. Metabolomic and proteomic analyses reveal that polyamine biosynthesis is upregulated in vemurafenib-resistant cancer, resulting in enhanced EIF5A hypusination, translation of mitochondrial proteins and oxidative phosphorylation. We also identify that sustained c-Myc levels in vemurafenib-resistant cancer are responsible for elevated polyamine biosynthesis. Finally, inhibition of polyamine biosynthesis or c-Myc reversed vemurafenib resistance both in vitro and in vivo in a xenograft model. With the polyamine biosynthesis signature correlated with poor prognosis in BRAF mutant melanoma patients, our findings reveal that the polyamine-hypusination-mitochondrial respiration pathway is an effective therapeutic target that can maximize the therapeutic efficacy of existing BRAF inhibitors.

2024-07-10 | GSE243344 | GEO

Arginine catabolism and polyamine biosynthesis pathway disparities within Francisella tularensis subpopulations

Project description:Arginine catabolism and polyamine biosynthesis pathway disparities within Francisella tularensis subpopulations

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Hypusine Biosynthesis in β Cells Links Polyamine Metabolism to Facultative Cellular Proliferation to Maintain Glucose Homeostasis

Project description:Deoxyhypusine synthase (DHPS) utilizes the polyamine spermidine to catalyze the hypusine modification of the mRNA translation factor eIF5A and promotes oncogenesis through poorly-defined mechanisms. Because germline deletion of Dhps is embryonically lethal, its role in normal postnatal cellular function in vivo remains unknown. We generated a mouse model that allows for inducible, postnatal deletion of Dhps specifically in postnatal islet β cells, which function to maintain glucose homeostasis. Removal of Dhps did not have an effect under normal physiologic conditions. However, upon development of insulin resistance, which induces β-cell proliferation, Dhps deletion caused alterations in proteins required for mRNA translation, reduced production of the cell cycle molecule Cyclin D2, impaired β-cell proliferation, and overt diabetes. We found that hypusine biosynthesis was downstream of protein kinase C-ζ and was required for c-Myc-induced proliferation. Our studies reveal a requirement for DHPS in β cells to link polyamines to mRNA translation to effect facultative cellular proliferation and glucose homeostasis.

2019-08-30 | GSE136581 | GEO

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