The natural polyamines and the immune system

Seiler, Nikolaus; Atanassov, Christo

doi:10.1007/978-3-0348-7156-3_4

Cited by 50 publications

(49 citation statements)

References 165 publications

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“…For example, simulation results showed that the two S. aureus USA300 isolates were the only strains capable of using spermidine as a sole source of carbon and nitrogen due to the presence of spermidine acetyltransferase (encoded for by speG). Spermidine is produced at high levels in areas of keratinocyte proliferation, inflammation, and wound healing (39), conditions under which S. aureus invades and causes skin infection. We experimentally confirmed that only S. aureus USA300 could grow in TSB media supplemented with 6 mM of spermidine, whereas S. aureus strains Newman and NCTC8325 could not (Fig.…”

Section: S Aureus Strains Can Be Differentiated Using Gem-predicted mentioning

confidence: 99%

Comparative genome-scale modelling of Staphylococcus aureus strains identifies strain-specific metabolic capabilities linked to pathogenicity

Bosi

Monk

Aziz

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

224

196

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Staphylococcus aureus is a preeminent bacterial pathogen capable of colonizing diverse ecological niches within its human host. We describe here the pangenome of S. aureus based on analysis of genome sequences from 64 strains of S. aureus spanning a range of ecological niches, host types, and antibiotic resistance profiles. Based on this set, S. aureus is expected to have an open pangenome composed of 7,411 genes and a core genome composed of 1,441 genes. Metabolism was highly conserved in this core genome; however, differences were identified in amino acid and nucleotide biosynthesis pathways between the strains. Genome-scale models (GEMs) of metabolism were constructed for the 64 strains of S. aureus. These GEMs enabled a systems approach to characterizing the core metabolic and panmetabolic capabilities of the S. aureus species. All models were predicted to be auxotrophic for the vitamins niacin (vitamin B3) and thiamin (vitamin B1), whereas strain-specific auxotrophies were predicted for riboflavin (vitamin B2), guanosine, leucine, methionine, and cysteine, among others. GEMs were used to systematically analyze growth capabilities in more than 300 different growth-supporting environments. The results identified metabolic capabilities linked to pathogenic traits and virulence acquisitions. Such traits can be used to differentiate strains responsible for mild vs. severe infections and preference for hosts (e.g., animals vs. humans). Genome-scale analysis of multiple strains of a species can thus be used to identify metabolic determinants of virulence and increase our understanding of why certain strains of this deadly pathogen have spread rapidly throughout the world.systems biology | mathematical modeling | pathogenicity | core genome | pangenome

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Section: S Aureus Strains Can Be Differentiated Using Gem-predicted mentioning

confidence: 99%

Comparative genome-scale modelling of Staphylococcus aureus strains identifies strain-specific metabolic capabilities linked to pathogenicity

Bosi

Monk

Aziz

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

224

196

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“…3 Arginase produces ornithine, the precursor for polyamines and proline, which are conducive to an environment of growth and repair. 4,5 Studies using cultured macrophages show that arginase also can regulate the production of nitric oxide by competing with nitric oxide synthases for arginine availability. 6,7 Cytokines govern the expression of both arginase and nitric oxide synthase (iNOS).…”

Section: Discussionmentioning

confidence: 99%

“…On the day of injury, samples were collected an average of 8 hours after injury (range [3][4][5][6][7][8][9][10][11][12][13][14][15][16]. Daily blood samples were obtained through indwelling arterial or central venous catheters from trauma patients in the ICU (up to 7 days).…”

Section: Peripheral Blood Mononuclear Cell Isolationmentioning

confidence: 99%

Arginase I Expression and Activity in Human Mononuclear Cells After Injury

Ochoa¹,

Bernard²,

O’Brien³

et al. 2001

Annals of Surgery

146

101

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ObjectiveTo determine the effect of trauma on arginase, an arginine-metabolizing enzyme, in cells of the immune system in humans. Summary Background DataArginase, classically considered an enzyme exclusive to the liver, is now known to exist in cells of the immune system. Arginase expression is induced in these cells by cytokines interleukin (IL) 4, IL-10, and transforming growth factor beta, corresponding to a T-helper 2 cytokine profile. In contrast, nitric oxide synthase expression is induced by IL-1, tumor necrosis factor, and gamma interferon, a T-helper 1 cytokine profile. Trauma is associated with a decrease in the production of nitric oxide metabolites and a state of immunosuppression characterized by an increase in the production of IL-4, IL-10, and transforming growth factor beta. This study tests the hypothesis that trauma increases arginase activity and expression in cells of the immune system. MethodsSeventeen severely traumatized patients were prospectively followed up in the intensive care unit for 7 days. Twenty volunteers served as controls. Peripheral mononuclear cells were isolated and assayed for arginase activity and expression, and plasma was collected for evaluation of levels of arginine, citrulline, ornithine, nitrogen oxides, and IL-10.

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“…Polyamine-depleted cells are stimulated to grow in the presence of exogenous polyamines [6][7][8]. Polyamines have specific roles in embryonic development [9], cell cycle [10,11], cancer [12,13], neurochemistry [14], as well as pulmonary [15] and immune system functions [16,17]. Cellular polyamines are regulated by a complex circuitry of synthesis, degradation, as well as cellular uptake and efflux [3][4][5]18].…”

Section: Introductionmentioning

confidence: 99%

Polyamines in cell growth and cell death: molecular mechanisms and therapeutic applications

Thomas¹

2001

CMLS, Cell. Mol. Life Sci.

780

577

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Polyamines are aliphatic cations with multiple functions and are essential for life. Cellular polyamine levels are regulated by multiple pathways such as synthesis from amino acid precursors, cellular uptake mechanisms that salvage polyamines from diet and intestinal microorganisms, as well as stepwise degradation and efflux. Investigations using polyamine biosynthetic inhibitors indicate that alterations in cellular polyamine levels modulate normal and cancer cell growth. Studies using transgenic mice overexpressing polyamine biosynthetic enzymes support a role of polyamines in carcinogenesis. Many, if not all, signal transduction pathways intersect with polyamine biosynthetic pathways and the regulation of intracellular polyamine levels. Direct binding of polyamines to DNA and their ability to modulate DNA-protein interactions appear to be important in the molecular mechanisms of polyamine action in cell proliferation. Consistent with the role of polyamines as facilitators of cell growth, several studies have shown their ability to protect cells from apoptosis. However, polyamines also have a role in facilitating cell death. The basis of these diverse cellular responses is currently not known. Cell death response might be partly mediated by the production of hydrogen peroxide during polyamine catabolism. In addition, the ability of polyamines to alter DNA-protein and protein-protein interactions might be disruptive to cellular functions, when abnormally high levels are accumulated due to defects in polyamine catabolic or efflux pathways. A large body of data indicates that polyamine pathway can be a molecular target for therapeutic intervention in several types cancers. Inhibitors of biosynthesis, polyamine analogues as well as oligonucleotide/polyamine analogue combinations are promising drug candidates for chemoprevention and/or treatment of cancer.

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The natural polyamines and the immune system

Cited by 50 publications

References 165 publications

Comparative genome-scale modelling of Staphylococcus aureus strains identifies strain-specific metabolic capabilities linked to pathogenicity

Comparative genome-scale modelling of Staphylococcus aureus strains identifies strain-specific metabolic capabilities linked to pathogenicity

Arginase I Expression and Activity in Human Mononuclear Cells After Injury

Polyamines in cell growth and cell death: molecular mechanisms and therapeutic applications

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