Arginine catabolism and polyamine biosynthesis pathway disparities within Francisella tularensis subpopulations
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA837875 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR19190200_1.fastq.gz | Fastqsanger.gz | |||
| SRR19190200_2.fastq.gz | Fastqsanger.gz | |||
| SRR19190300_1.fastq.gz | Fastqsanger.gz | |||
| SRR19190300_2.fastq.gz | Fastqsanger.gz | |||
| SRR19190101_1.fastq.gz | Fastqsanger.gz |
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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: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 speHEA 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 in vitro fitness. Our ongoing studies on amino acid and polyamine flux within hypervirulent A.I strains should provide a better understanding of the factors that contribute to F. tularensis pathogenicity.
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Project description:Grapes (Vitis vinifera L.) are economically the most important fruit crop worldwide. However, the complexity of molecular and biochemical events that lead to ripening of nonclimacteric fruits is not fully understood. In particular the role of polyaminesM-BM-4 catabolism has been little explored. Ripening of Trincadeira grapes submitted to mock and guazatine treatments, a potent inhibitor of polyamine oxidase activity, was studied taking into account the transcriptional and metabolic profilings complemented with biochemical data. The mRNA expression profiles of one time point (EL 38) corresponding to harvest stage was compared between mock and guazatine treatments using the Affymetrix GrapeGenM-BM-. genome array containing 23096 probesets corresponding to 18711 unique sequences. A total of 2113 probesets (1877 unigenes) were significantly differentially expressed (1.5 fold) between these samples. These unigenes were assigned to the functional categories of M-bM-^@M-^\metabolismM-bM-^@M-^], M-bM-^@M-^\regulation overviewM-bM-^@M-^], M-bM-^@M-^\signalingM-bM-^@M-^], M-bM-^@M-^\cellular processM-bM-^@M-^], M-bM-^@M-^\transport overviewM-bM-^@M-^], M-bM-^@M-^\response to stimulus, stressM-bM-^@M-^], M-bM-^@M-^\diverse/miscellaneous functionsM-bM-^@M-^], M-bM-^@M-^\xenoprotein, transposable elementM-bM-^@M-^], M-bM-^@M-^\developmentM-bM-^@M-^] and M-bM-^@M-^\unknownM-bM-^@M-^]. Quantitative RT-PCR validated microarrays results being carried out for seven selected genes and three developmental stages (EL 35, EL 36 and EL 38). Functional enrichment analysis revealed that genes involved in amino acid, carbohydrate and water transport were more up-regulated in mock treated samples which may suggest that the strong dehydrated phenotype obtained in guazatine treated samples may be due to impaired transport mechanisms. In addition, genes involved in terpenesM-BM-4 metabolism were differentially expressed between guazatine and mock treated samples. Altogether, the results support an important role of polyamine catabolism in normal grape ripening namely in aroma development and cell expansion. 1 time point in 2010 season at EL 38. 3 biological replicates. 2 treatments
2013-09-30 | E-GEOD-44823 | biostudies-arrayexpress
Project description:Grapes (Vitis vinifera L.) are economically the most important fruit crop worldwide. However, the complexity of molecular and biochemical events that lead to ripening of nonclimacteric fruits is not fully understood. In particular the role of polyamines´ catabolism has been little explored. Ripening of Trincadeira grapes submitted to mock and guazatine treatments, a potent inhibitor of polyamine oxidase activity, was studied taking into account the transcriptional and metabolic profilings complemented with biochemical data. The mRNA expression profiles of one time point (EL 38) corresponding to harvest stage was compared between mock and guazatine treatments using the Affymetrix GrapeGen® genome array containing 23096 probesets corresponding to 18711 unique sequences. A total of 2113 probesets (1877 unigenes) were significantly differentially expressed (1.5 fold) between these samples. These unigenes were assigned to the functional categories of “metabolism”, “regulation overview”, “signaling”, “cellular process”, “transport overview”, “response to stimulus, stress”, “diverse/miscellaneous functions”, “xenoprotein, transposable element”, “development” and “unknown”. Quantitative RT-PCR validated microarrays results being carried out for seven selected genes and three developmental stages (EL 35, EL 36 and EL 38). Functional enrichment analysis revealed that genes involved in amino acid, carbohydrate and water transport were more up-regulated in mock treated samples which may suggest that the strong dehydrated phenotype obtained in guazatine treated samples may be due to impaired transport mechanisms. In addition, genes involved in terpenes´ metabolism were differentially expressed between guazatine and mock treated samples. Altogether, the results support an important role of polyamine catabolism in normal grape ripening namely in aroma development and cell expansion.
2013-09-30 | GSE44823 | 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.
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Project description:In other bacteria, arginine induces the expression of genes involved in arginine catabolism. This study obtained the identification of genes involved in the arginine metabolism of Mycobacterium tuberculosis. Mycobacterium tuberculosis was cultured with arginine or ammonium chloride as sole nitrogen source. In the log phase of growth, RNA was isolated and whole genome expression was determined. The study contains three biological replicates.
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Project description:In other bacteria, arginine induces the expression of genes involved in arginine catabolism. This study obtained the identification of genes involved in the arginine metabolism of Mycobacterium tuberculosis.
2015-04-01 | GSE67445 | GEO
Project description:Metabolic reprogramming is a hallmark of cancer. However, mechanisms underlying metabolic reprogramming and how altered metabolism in turn enhances tumorigenicity are poorly understood. Here, we report that arginine levels are elevated in hepatocellular carcinoma (HCC) despite reduced expression of arginine synthesis genes, in murine and patient tumors. Tumor cells accumulate high levels of arginine due to increased uptake and reduced arginine-to-polyamine conversion. Importantly, the high levels of arginine promote tumor formation via further metabolic reprogramming, including changes in glucose, amino acid, nucleotide, and fatty acid metabolism. Mechanistically, arginine binds RNA-binding motif protein 39 (RBM39) to control expression of metabolic genes. RBM39-mediated upregulation of asparagine synthesis leads to enhanced arginine uptake, creating a positive feedback loop to sustain high arginine levels and oncogenic metabolism. Thus, arginine is a second messenger-like molecule that reprograms metabolism to promote tumor growth.
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2014-07-16 | E-GEOD-56060 | biostudies-arrayexpress
Project description:SUMMARY Non-Hispanic Black/African American (Black/AA) men in the United States have disproportionally higher incidence and mortality rates of lung cancer compared to non-Hispanic White (NHW) men. Biological factors are believed to play critical roles in driving the disparities. Nevertheless, large-scale genomic studies fail to identify significant somatic differences in lung cancer driver genes contributing to the disparities. Elevated expression of protein arginine methyltransferases (PRMTs) correlating with poorer prognosis is observed in many cancer types. Here, we observed a higher PRMT6 expression in lung cancer of Black/AA men compared to NHW men. PRMT6 formed a heteromer complex with PRMT1 to catalyze arginine methylation of interleukin enhancer-binding factor 2 essential for cell proliferation. Disrupting PRMT1/PRMT6 heteromer complex by a competitive peptide reduced cell proliferation in non-small cell lung cancer cell lines and lung cancer patient-derived organoids. This work implicates that PRMT1/PRMT6 heteromer complex contributes to poorer lung cancer outcomes in Black/AA men vs. NHW men that could serve as a target to eliminate cancer health disparities.
2023-12-15 | MSV000093674 | MassIVE