bims-polyam Biomed News
on Polyamines
Issue of 2020‒10‒25
nine papers selected by
Alexander Ivanov
Engelhardt Institute of Molecular Biology

  1. Front Microbiol. 2020 ;11 578533
    Ayoola MB, Nakamya MF, Shack LA, Park S, Lim J, Lee JH, Ross MK, Eoh H, Nanduri B.
      The global burden of invasive pneumococcal diseases, including pneumonia and sepsis, caused by Streptococcus pneumoniae, a Gram-positive bacterial pathogen, remains a major global health risk. The success of pneumococcus as a pathogen can be attributed to its ability to regulate the synthesis of capsular polysaccharide (CPS) during invasive disease. We previously reported that deletion of a putative lysine decarboxylase (LDC; ΔSP_0916) in pneumococcal serotype 4 (TIGR4) results in reduced CPS. SP_0916 locus is annotated as either an arginine or a LDC in pneumococcal genomes. In this study, by biochemical characterization of the recombinant SP_0916, we determined the substrate specificity of SP_0916 and show that it is an arginine decarboxylase (speA/ADC). We also show that deletion of the polyamine transporter (potABCD) predicted to import putrescine and spermidine results in reduced CPS, while deletion of spermidine synthase (speE) for the conversion of putrescine to spermidine had no impact on the capsule. Targeted metabolomics identified a correlation between reduced levels of agmatine and loss of capsule in ΔspeA and ΔpotABCD, while agmatine levels were comparable between the encapsulated TIGR4 and ΔspeE. Exogenous supplementation of agmatine restored CPS in both ΔpotABCD and ΔspeA. These results demonstrate that agmatine is critical for regulating the CPS, a predominant virulence factor in pneumococci.
    Keywords:  Streptococcus pneumoniae; agmatine; capsular polysaccharide; metabolomics; polyamines
  2. Anal Chim Acta. 2020 Oct 23. pii: S0003-2670(20)30864-3. [Epub ahead of print]1135 38-46
    Wang L, Ding H, Tang H, Cao D, Ran X.
      Polyamines (such as spermine, spermidine) play important roles in biomedical and food field. The elevated polyamines have been proposed to serve as target analytes for monitoring meat spoilage. Because of structural similarity and low concentration of polyamines in real samples, it is exceedingly challenging to design and develop sensitive probes for visual detection of polyamines. To address this issue, a highly efficient probe was reported based on a newly developed chromophore reaction between lactam-fused aza-BODIPY (abbreviation: LAB) and polyamines by virtue of unique multiple amino groups character of polyamines. This chromophore reaction includes a kinetic-controllable reaction of a B-N bond cleavage by polyamines followed by a fast hydrolysis reaction to yield much smaller conjugated molecules. With 130 nm hypsochromic shift of the absorption peak and up to 99% fluorescence quenching within 1 min, LAB can be used as a highly sensitive fluorescent probe for detection of polyamines solution and monitoring fish spoilage with synchronous colorimetric and fluorescent changes.
    Keywords:  Chromophore reaction; Fluorescent probe; Lactam-fused aza-BODIPY; Polyamine detection
  3. Int J Mol Sci. 2020 Oct 21. pii: E7789. [Epub ahead of print]21(20):
    Alharbi B, Hunt JD, Dimitrova S, Spadafora ND, Cort AP, Colombo D, Müller CT, Ghuge SA, Davoli D, Cona A, Mariotti L, Picciarelli P, de Graaf B, Rogers HJ.
      Polyamines (PAs) are essential metabolites in plants performing multiple functions during growth and development. Copper-containing amine oxidases (CuAOs) catalyse the catabolism of PAs and in Arabidopsis thaliana are encoded by a gene family. Two mutants of one gene family member, AtCuAOδ, showed delayed seed germination, leaf emergence, and flowering time. The height of the primary inflorescence shoot was reduced, and developmental leaf senescence was delayed. Siliques were significantly longer in mutant lines and contained more seeds. The phenotype of AtCuAOδ over-expressors was less affected. Before flowering, there was a significant increase in putrescine in AtCuAOδ mutant leaves compared to wild type (WT), while after flowering both spermidine and spermine concentrations were significantly higher than in WT leaves. The expression of GA (gibberellic acid) biosynthetic genes was repressed and the content of GA1, GA7, GA8, GA9, and GA20 was reduced in the mutants. The inhibitor of copper-containing amine oxidases, aminoguanidine hydrochloride, mimicked the effect of AtCuAOδ mutation on WT seed germination. Delayed germination, reduced shoot height, and delayed flowering in the mutants were rescued by GA3 treatment. These data strongly suggest AtCuAOδ is an important gene regulating PA homeostasis, and that a perturbation of PAs affects plant development through a reduction in GA biosynthesis.
    Keywords:  copper-containing amine oxidases; flowering; gibberellic acid; polyamines; putrescine; senescence
  4. PLoS One. 2020 ;15(10): e0234832
    Miller M, Rogers JC, Badham MA, Cadenas L, Brightwell E, Adams J, Tyler C, Sebahar PR, Haussener TJ, Reddy HRK, Looper RE, Williams DL.
      Biofilm-impaired tissue is a significant factor in chronic wounds such as diabetic foot ulcers. Most, if not all, anti-biotics in clinical use have been optimized against planktonic phenotypes. In this study, an in vitro assessment was performed to determine the potential efficacy of a first-in-class series of antibiofilm antibiotics and compare outcomes to current clinical standards of care. The agent, CZ-01179, was formulated into a hydrogel and tested against mature biofilms of a clinical isolate of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa ATCC 27853 using two separate methods. In the first method, biofilms were grown on cellulose discs on an agar surface. Topical agents were spread on gauze and placed over the biofilms for 24 h. Biofilms were quantified and imaged with confocal and scanning electron microscopy. In the second method, biofilms were grown on bioabsorbable collagen coupons in a modified CDC biofilm reactor. Coupons were immersed in treatment for 24 h. The first method was limited in its ability to assess efficacy. Efficacy profiles against biofilms grown on collagen were more definitive, with CZ-01179 gel eradicating well-established biofilms to a greater degree compared to clinical standards. In conclusion, CZ-01179 may be a promising topical agent that targets the biofilm phenotype. Pre-clinical work is currently being performed to determine the translatable potential of CZ-01179 gel.
  5. Physiol Mol Biol Plants. 2020 Oct;26(10): 2035-2045
    Sreelekshmi R, Siril EA.
      Hyperhydricity (HH) is a physiological disorder that frequently occurs in plant tissue cultures, affecting healthy growth and development of clonal plants. The primary cultures raised in Murashige and Skoog (MS) medium supplemented with 2.5 µM N6-benzyladenine (BA) produced normal microshoot (6.3 shoots/ culture) with least HH. However, the third subculture onwards, HH becomes a major problem. The role of ethylene on HH induction through stomatal closure mechanism were proved by the supplementation of ethephon (5 µM) in the culture medium containing 2.5 µM BA. In the present study, the application of polyamines (putrescine, spermidine, or spermine) to minimize the HH was examined. Supplementation of 5 µM spermine in MS medium significantly reduced the percentage of HH to 0.33%, in contrast to control (100%), while a maximum number of healthy reverted shoots (11.0) were observed in 5 µM spermidine treatment. The addition of polyamines effectively reduced H2O2 content (50%) characterized by increased chlorophyll content with proper stomatal morphology. The relative gene expression profile of ethylene biosynthesis genes, 1-Aminocyclopropane-1-carboxylase synthase (ACS1) and 1-Aminocyclopropane-1-carboxylic acid oxidase (ACO1) at 5 µM spermine added medium was 1.09 and 1.3 over normal (1) or HH cultures (1.93 and 2.53) respectively, and thus directed restoration of normal morphology of shoots. The present finding in brief, forward a novel method to regulate HH in terms of endogenous ethylene by adopting polyamines exposure and the procedure can be applied to many other plants facing similar HH problems.
    Keywords:  ACC synthase; Ethephon; Spermine; Stomatal bioassay; Vitrification
  6. Int J Neurosci. 2020 Oct 22. 1-15
    Borikar SP, Dongare SI, Danao KR.
      Infection and inflammation are important pathological mechanism underlying neurodegenerative disorders and altered behavioral outcomes including learning and memory deficits. We tested the effect of agmatine in lipopolysaccharides (LPS)-induced learning and memory deficits in mice. Following 7 days of LPS administration animals were subjected to novel object recognition (NOR) test on day 8 and Morris water maze (MWM) test on days 9-13 for the assessment of its effect on learning and memory. Seven of days LPS treatment but not for 1 or 3 days, produced significant deficits in recognition and spatial memory in mice. In LPS pre-treated mice, agmatine treatment on day 8 resulted in the more exploration to the novel object. Agmatine treatment (day 8-12) in mice showed reduction in the escape latency and time spent in the target quadrant (probe trial) in the MWM test. However, co-administration of agmatine with LPS in mice for 7 days showed higher discrimination index in NOR test on Day-8. This co-administration also showed decrease in escape latency as well as time spent in the target quadrant in MWM test on days 9-13 as compared to LPS control group. Therefore, the results of this present study imply the protective and curative effects of agmatine against LPS mediated loss of memory functions in experimental animals. Highlights1. Subchronic but not acute lipopolysaccharides induce memory deficits2. Lipopolysaccharides impairs recognition and spatial memory in mice.3. Agmatine prevents lipopolysaccharides-induced loss of memory.4. Agmatine reverses deficits in learning and memory by lipopolysaccharides.
    Keywords:  Learning and memory; Lipopolysaccharide; Morris water maze; Neuroinflammation; Novel object recognition test
  7. Biochim Biophys Acta Proteins Proteom. 2020 Oct 14. pii: S1570-9639(20)30202-8. [Epub ahead of print] 140555
    Montioli R, Bellezza I, Desbats MA, Voltattorni CB, Salviati L, Cellini B.
      Gyrate Atrophy (GA) of the choroid and retina (MIM# 258870) is an autosomal recessive disorder due to mutations of the OAT gene encoding ornithine-delta-aminotransferase (OAT), associated with progressive retinal deterioration and blindness. The disease has a theoretical global incidence of approximately 1:1,500,000. OAT is mainly involved in ornithine catabolism in adults, thus explaining the hyperornithinemia as hallmark of the disease. Patients are treated with an arginine-restricted diet, to limit ornithine load, or the administration of Vitamin B6, a precursor of the OAT coenzyme pyridoxal phosphate. Although the clinical and genetic aspects of GA are known for many years, the enzymatic phenotype of pathogenic variants and their response to Vitamin B6, as well as the molecular mechanisms explaining retinal damage, are poorly clarified. Herein, we provide an overview of the current knowledge on the biochemical properties of human OAT and on the molecular, cellular, and clinical aspects of GA.
    Keywords:  Gyrate atrophy of the choroid and retina; Ornithine aminotransferase; Pathogenic variants; Pyridoxal phosphate; Retinal cells; Vitamin B6
  8. Sci Rep. 2020 Oct 20. 10(1): 17858
    Salvi D, Tavladoraki P.
      Polyamine oxidases (PAOs) are characterized by a broad variability in catalytic properties and subcellular localization, and impact key cellular processes in diverse organisms. In the present study, a comprehensive phylogenetic analysis was performed to understand the evolution of PAOs across the three domains of life and particularly within eukaryotes. Phylogenetic trees show that PAO-like sequences of bacteria, archaea, and eukaryotes form three distinct clades, with the exception of a few procaryotes that probably acquired a PAO gene through horizontal transfer from a eukaryotic donor. Results strongly support a common origin for archaeal PAO-like proteins and eukaryotic PAOs, as well as a shared origin between PAOs and monoamine oxidases. Within eukaryotes, four main lineages were identified that likely originated from an ancestral eukaryotic PAO before the split of the main superphyla, followed by specific gene losses in each superphylum. Plant PAOs show the highest diversity within eukaryotes and belong to three distinct clades that underwent to multiple events of gene duplication and gene loss. Peptide deletion along the evolution of plant PAOs of Clade I accounted for further diversification of function and subcellular localization. This study provides a reference for future structure-function studies and emphasizes the importance of extending comparisons among PAO subfamilies across multiple eukaryotic superphyla.
  9. Plant Physiol Biochem. 2020 Oct 08. pii: S0981-9428(20)30482-4. [Epub ahead of print]157 79-92
    Xu J, Yang J, Xu Z, Zhao D, Hu X.
      The study tested the function of exogenous spermine (Spm) in resisting salinity-alkalinity stress in tomato seedlings and found that tomato Spm synthase gene (SlSPMS) was involved in this regulation. The tomato seedlings cultivated in normal conditions or salinity-alkalinity conditions were irrigated with 100 ml one strength Hoagland nutrient solution 100 ml mixed solution (5 ml 300 mmol/L NaCl, 45 ml 300 mmol/L Na2SO4, 45 ml 300 mmol/L NaHCO3, and 5 ml 300 mmol/L Na2CO3 (pH = 8.90)) every 2 days, respectively. The 0.5 mM Spm pretreatment improved superoxide dismutase (SOD; EC activity, catalase (CAT; EC activity, ascorbate peroxidase (APX; EC activity, and glutathione reductase (GR; EC activity and decreased endogenous hydrogen peroxide (H2O2) content, malondialdehyde (MDA) content, and relative electrical conductivity (REC) in tomato leaves. Na+ content declined and K+ concentration rose in tomato seedlings when pre-treated with Spm. However the results showed that under salinity-alkalinity stress, silencing of SlSPMS with virus-induced gene silencing had lower antioxidant enzyme activities and higher Na+ content and lower K+ content than normal tomato seedlings, meaning that they had low salinity-alkalinity tolerance. Exogenous Spm could not reconstruct the tolerance to salinity-alkalinity stress in SlSPMS gene-silencing tomato seedlings. Taken together, exogenous Spm could induce the expression level of SlSPMS, which regulated the antioxidant enzyme system and ion homeostasis in tomato seedlings living in salinity-alkalinity environment, thereby improving the ability of tomato seedlings to resist salinity-alkalinity stress.
    Keywords:  Ion homeostasis; Salinity–alkalinity; SlSPMS gene silencing; Spermine; Tomato seedlings