Polyamine biosynthesis in Salmonella
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ABSTRACT:
PROVIDER: PRJEB35646 | ENA |
REPOSITORIES: ENA
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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
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
Project description:The speG gene has been reported to regulate polyamine metabolism in Escherichia coli and Shigella, but its role in Salmonella remains unknown. Our preliminary studies have revealed that speG widely affects the transcriptomes of infected in vitro M and Caco-2 cells and that it is required for the intracellular replication of Salmonella enterica serovar Typhimurium (S. Typhimurium) in HeLa cells. In this study, we demonstrated that speG plays a time-dependent and cell type-independent role in the intracellular replication of S. Typhimurium. Moreover, high-performance liquid chromatography of four major polyamines demonstrated putrescine, spermine, and cadaverine as the leading polyamines in S. Typhimurium. The deletion of speG significantly increased the levels of the three polyamines in intracellular S. Typhimurium, suggesting the inhibitory effect of speG on the biosynthesis of these polyamines. The deletion of speG was associated with elevated levels of these polyamines in the attenuated intracellular replication of S. Typhimurium in host cells, which was subsequently validated by the dose-dependent suppression of intracellular proliferation after the addition of the polyamines. Furthermore, our RNA transcriptome analysis of S. Typhimurium SL1344 and its speG mutant outside and inside Caco-2 cells revealed that speG regulates the genes with documented virulence in flagellar biosynthesis, fimbrial expression, and functions of types III and I secretion systems. speG also affects the expression of genes that have been rarely reported to correlate with polyamine metabolism, including those associated with the periplasmic nitrate reductase system, glucarate metabolism, the phosphotransferase system, cytochromes, and the succinate reductase complex in S. Typhimurium in the mid-log growth phase, as well as those in the ilv–leu and histidine operons of intracellular S. Typhimurium after invasion in Caco-2 cells. In the present study, we characterized the phenotypes and transcriptome effects of speG in S. Typhimurium and reviewed the relevant literature to facilitate a more comprehensive understanding of the key role of speG in the polyamine metabolism and virulence regulation of Salmonella.
2017-08-22 | GSE102885 | GEO
Project description:Arginine catabolism and polyamine biosynthesis pathway disparities within Francisella tularensis subpopulations
| PRJNA837875 | ENA
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
Project description:Pancreatic ductal adenocarcinoma (PDA) cells have a distinct dependence on de novo ornithine synthesis from glutamine via ornithine aminotransferase (OAT), which supports polyamine synthesis and is required for tumor growth. This directional OAT activity is normally largely restricted to infancy and contrasts with the reliance of most adult normal tissues and other cancer types on arginase (ARG) to generate arginine-derived ornithine, the substrate for polyamine synthesis. This dependence associates with arginine depletion in PDA tumor microenvironment, and is driven by mutant KRAS, which induces the expression of OAT and polyamine synthesis enzymes, including the rate-limiting enzyme ornithine decarboxylase-1 (ODC1). Loss of OAT, but not ARG2, largely mimics loss of ODC1, altering the transcriptional profiles in PDA cells, which in turn correlate with alterations in open chromatin states.
2023-01-01 | GSE193411 | GEO
Project description:Polyamines, including putrescine (PUT), spermidine (SPD) and spermine (SPM), are abundant polycations supporting various cellular functions. Their cellular content is tightly controlled by biosynthesis, degradation and uptake or export via the polyamine transport system (PTS). However, the mammalian PTS remains poorly characterized. Mutated Chinese hamster ovary cells, CHO-MG, are frequently used to study the PTS owing to their phenotype of reduced polyamine uptake and resistance to methylglyoxal bis-(guanylhydrazone) (MGBG), a toxic polyamine biosynthesis inhibitor. Yet, the underlying genetic defect remains enigmatic. We recently proved that the P5B-type ATPase, ATP13A2, is a polyamine transporter and here, we analyzed whether the P5B-type ATPases are deficient in CHO-MG. Label-free shogun proteomics found that ATP13A3 expression is reduced in CHO-MG. Mutations in the ATP13A3 gene were found to critically disturb the protein sequence. Interestingly, depleting ATP13A3 in the wild-type CHO cells induced a CHO-MG phenotype, whereas its complementation in CHO-MG rescued the phenotype. Together, we demonstrate that defective ATP13A3 contributes to the CHO-MG phenotype, designating ATP13A3 as a new member of the mammalian PTS that may partially overlap in function with ATP13A2.
2020-12-09 | PXD020559 | Pride
Project description:Francisella tularensis is a highly infectious zoonotic pathogen with as few as 10 organisms causing tularemia, a disease that is fatal if untreated. Although F. tularensis subspecies tularensis (type A) and subspecies holarctica (type B) share over 99.5% average nucleotide identity, notable differences exist in genomic organization and pathogenicity. The type A clade has been further divided into subtypes A.I and A.II, with A.I strains being recognized as some of the most virulent bacterial pathogens known. In this study, we report on major disparities that exist between the F. tularensis subpopulations in arginine catabolism and subsequent polyamine biosynthesis. The genes involved in these pathways include the speDEA and aguAB operons, along with metK. In the hypervirulent F. tularensis A.I clade, such as the A.I prototype strain SCHU S4, these genes were found to be intact and highly transcribed. In contrast, both subtype A.II and type B strains have a truncated speA gene, while the type B clade also has a disrupted aguA and truncated aguB. Ablation of the chromosomal speE gene that encodes a spermidine synthase reduced subtype A.I SCHU S4 growth rate, whereas the growth rate of type B LVS was enhanced. These results demonstrate that spermine synthase SpeE promotes faster replication in the F. tularensis A.I clade, whereas type B strains do not rely on this enzyme for fitness. Our ongoing studies on metabolism should provide a better understanding of the factors that contribute to F. tularensis pathogenicity.
2022-07-13 | GSE202948 | GEO
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
Project description:Polyamine metabolism in the human placenta
| PRJEB45391 | ENA