bims-polyam 2022-07-24 papers

bims-polyam

Biomed News

on Polyamines

Issue of 2022–07–24
seven papers selected by
Sebastian J. Hofer, University of Graz

Polyamines mitigate the destructive impacts of salinity stress by enhancing photosynthetic capacity, antioxidant defense system and upregulation of calvin cycle-related genes in rapeseed (Brassica napus L.).
Exogenous spermidine regulates the anaerobic enzyme system through hormone concentrations and related-gene expression in Phyllostachys praecox roots under flooding stress.
Fusobacterium nucleatum Metabolically Integrates Commensals and Pathogens in Oral Biofilms.
Design and synthesis of hybrid compounds as novel drugs and medicines.
Bi-allelic variants in DOHH, catalyzing the last step of hypusine biosynthesis, are associated with a neurodevelopmental disorder.
The untapped potential of spermidine alkaloids: Sources, structures, bioactivities and syntheses.
Influence of polyamine production and proteolytic activities of co-cultivated bacteria on histamine production by Morganiella morganii.

Saudi J Biol Sci. 2022 May;29(5): 3675-3686

Polyamines mitigate the destructive impacts of salinity stress by enhancing photosynthetic capacity, antioxidant defense system and upregulation of calvin cycle-related genes in rapeseed (Brassica napus L.).

Abdelaleim I ElSayed, Azza H Mohamed, Mohammed Suhail Rafudeen, Ahmad A Omar, Mohamed F Awad, Elsayed Mansour.

  Salinity is widespread environmental stress that poses great obstacles to rapeseed development and growth. Polyamines are key plant growth regulators that play a pivotal role in regulating salt tolerance. Rapeseed (Brassica napus L.) seedlings were treated by spermine (Spm) and spermidine (Spd) versus untreated control under salt stress conditions. It was detected that the Spd-treated plants had significantly elevated chlorophyll and proline content and maintained higher photosystem II (PSII) activity than those treated with Spm as well as untreated control under salt-stressed conditions. Similarly, Spd alleviated the devastating effects of NaCl stress on CO2 assimilation and significantly elevated Rubisco activity (ribulose 1,5-bisphosphate carboxylase/oxygenase). The application of Spd also enhanced the activities of different antioxidant enzymes under NaCl stress. It modulated their respective transcription levels, including ascorbate peroxidase (APX), catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), and dehydroascorbate reductase (DHAR). In addition, exogenously sprayed Spd enhanced the polyamine pathway as observed by upregulated transcription of polyamine oxidase (PAO) and diamine oxidase (DAO). The Spd application enhanced expressions of Calvin cycle enzyme related genes such as Rubisco small subunit, Rubisco large subunit, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), 3-phosphoglyceric acid kinase (PGK), triose-3-phosphate isomerase (TPI), fructose-1,6-bisphosphate aldolase (FBA), sedoheptulose-1,7-bisphosphatase (SBPase), and fructose-1,6-bisphosphate phosphatase (FBPase). Consequently, this study demonstrates that exogenous application of Spd has a valuable role in regulating antioxidant enzyme activity, polyamine pathway, and Calvin cycle enzyme-related genes to alleviate salt stress damage in the plants.

Keywords:  Gene expression; Photosynthesis; Rapeseed; Salinity stress; Spermidine; Spermine

DOI:  https://doi.org/10.1016/j.sjbs.2022.02.053
Plant Physiol Biochem. 2022 Jul 16. pii: S0981-9428(22)00305-9. [Epub ahead of print]186 182-196

Exogenous spermidine regulates the anaerobic enzyme system through hormone concentrations and related-gene expression in Phyllostachys praecox roots under flooding stress.

Jianshuang Gao, Zhuangzhuang Qian, Yuhe Zhang, Shunyao Zhuang.

   PURPOSE: Acclimation to hypoxia and anoxia is important in various ecological systems, especially flooded soil. Phyllostachys pracecox is sensitive to flooding, and therefore, it is important to explore ways of alleviating hypoxia stress in the roots. In this study, we investigated the regulatory effect of spermidine (Spd) on flooded P. praecox seedlings.
METHODS: A batch experiment was carried out in roots treated with Spd under flooding for eight days. The following factors were subsequently measured: growth, survival rate, root respiratory activity, soluble protein and anaerobic respiration enzyme contents (pyruvate decarboxylase, PDC; alcohol dehydrogenase, ADH; lactate dehydrogenase, LDH; alanine aminotransferase, AlaAT), S-adenosylmethionine decarboxylase (SAMDC), nitrate reductase (NR), ACC oxidase (ACO) and ACC synthetase (ACS) activities, free Spd, spermine (Spm) and the diamine precursor putrescine (Put) content, indole-3-acetic acid (IAA) and abscisic acid (ABA) content, ethylene emissions and expression of hormone-related genes.
RESULTS: Application of Spd promoted root growth (root length, volume, surface and dry weight) and root respiratory inhibition, improved the soluble protein content, and reduced the O2·- production rate, H2O2 and MDA content to alleviate the damage of roots under flooding. A significant increase in SAMDC activity, and ABA and IAA contents were also observed, along with a reduction in ethylene emissions, NR, ACO and ACS activities (p < 0.05). Exogenous Spd increased the free Spd and Spm contents in the P. praecox roots, but decreased the free Put content. Taken together, these findings suggest that hypoxia stress was alleviated. Moreover, exogenous Spd up-regulated the expression of auxin-related genes ARF1, AUX1, AUX2, AUX3 and AUX4, and down-regulated the expression of ethylene-related ACO and ACS genes during flooding. In addition, correlation and RDA analysis showed that ARF1, ACO and ACS significantly promoted the expression of auxin, ACO and ACS enzyme activities, respectively (p < 0.05), while ADH, NR, AlaAT, ethylene emissions, Put, Spd, ACS and ACO were significantly correlated with ACS, ACO, and auxin-related gene expression (p < 0.05). Overall, ethylene emissions, ACS and ACO were identified as the main drivers of ethylene and auxin-related gene structure.
CONCLUSIONS: These results suggest that Spd regulated hormone concentrations, the content of Spd, Spm and Put, and related gene expression, in turn regulating physiological changes such as anaerobic enzyme activity, mitigating flooding stress in the roots and improving overall growth. Spd therefore has the potential to improve the adaptability of P. praecox to flooding stress.

Keywords:  Anaerobic enzyme activity; Flooding; Gene expression; Hormones; Phyllostachys praecox; Spermidine

DOI:  https://doi.org/10.1016/j.plaphy.2022.07.002
mSystems. 2022 Jul 19. e0017022

Fusobacterium nucleatum Metabolically Integrates Commensals and Pathogens in Oral Biofilms.

Akito Sakanaka, Masae Kuboniwa, Shuichi Shimma, Samar A Alghamdi, Shota Mayumi, Richard J Lamont, Eiichiro Fukusaki, Atsuo Amano.

  Fusobacterium nucleatum is a common constituent of the oral microbiota in both periodontal health and disease. Previously, we discovered ornithine cross-feeding between F. nucleatum and Streptococcus gordonii, where S. gordonii secretes ornithine via an arginine-ornithine antiporter (ArcD), which in turn supports the growth and biofilm development of F. nucleatum; however, broader metabolic aspects of F. nucleatum within polymicrobial communities and their impact on periodontal pathogenesis have not been addressed. Here, we show that when cocultured with S. gordonii, F. nucleatum increased amino acid availability to enhance the production of butyrate and putrescine, a polyamine produced by ornithine decarboxylation. Coculture with Veillonella parvula, another common inhabitant of the oral microbiota, also increased lysine availability, promoting cadaverine production by F. nucleatum. We confirmed that ArcD-dependent S. gordonii-excreted ornithine induces synergistic putrescine production, and mass spectrometry imaging revealed that this metabolic capability creates a putrescine-rich microenvironment on the surface of F. nucleatum biofilms. We further demonstrated that polyamines caused significant changes in the biofilm phenotype of a periodontal pathogen, Porphyromonas gingivalis, with putrescine accelerating the biofilm life cycle of maturation and dispersal. This phenomenon was also observed with putrescine derived from S. gordonii-F. nucleatum coculture. Lastly, analysis of plaque samples revealed cooccurrence of P. gingivalis with genetic modules for putrescine production by S. gordonii and F. nucleatum. Overall, our results highlight the ability of F. nucleatum to induce synergistic polyamine production within multispecies consortia and provide insight into how the trophic web in oral biofilm ecosystems can eventually shape disease-associated communities. IMPORTANCE Periodontitis is caused by a pathogenic shift in subgingival biofilm ecosystems, which is accompanied by alterations in microbiome composition and function, including changes in the metabolic activity of the biofilm, which comprises multiple commensals and pathogens. While Fusobacterium nucleatum is a common constituent of the supra- and subgingival biofilms, its metabolic integration within polymicrobial communities and the impact on periodontal pathogenesis are poorly understood. Here, we report that amino acids supplied by other commensal bacteria induce polyamine production by F. nucleatum, creating polyamine-rich microenvironments. Polyamines reportedly have diverse functions in bacterial physiology and possible involvement in periodontal pathogenesis. We show that the F. nucleatum-integrated trophic network yielding putrescine from arginine through ornithine accelerates the biofilm life cycle of Porphyromonas gingivalis, a periodontal pathogen, from the planktonic state through biofilm formation to dispersal. This work provides insight into how cooperative metabolism within oral biofilms can tip the balance toward periodontitis.

Keywords:  Fusobacterium nucleatum; Porphyromonas gingivalis; arginine deiminase system; metabolic cross-feeding; oral biofilms; periodontitis; polyamines

DOI:  https://doi.org/10.1128/msystems.00170-22
RSC Adv. 2022 Jun 29. 12(30): 19470-19484

Design and synthesis of hybrid compounds as novel drugs and medicines.

Abdulaziz H Alkhzem, Timothy J Woodman, Ian S Blagbrough.

The development of highly effective conjugate chemistry approaches is a way to improve the quality of drugs and of medicines. The aim of this paper is to highlight and review such hybrid compounds and the strategies underpinning their design. A variety of unique hybrid compounds provide an excellent toolkit for novel biological activity, e.g. anticancer and non-viral gene therapy (NVGT), and as templates for killing bacteria and preventing antibiotic drug resistance. First we discuss the anticancer potential of hybrid compounds, containing daunorubicin, benzyl- or tetrahydroisoquinoline-coumarin, and cytotoxic NSAID-pyrrolizidine/indolizine hybrids, then NVGT cationic lipid-based delivery agents, where steroids or long chain fatty acids as the lipid moiety are bound to polyamines as the cationic moiety. These polyamines can be linear as in spermidine or spermine, or on a polycyclic sugar template, aminoglycosides kanamycin and neomycin B, the latter substituted with six amino groups. They are highly efficient for the delivery of both fluorescent DNA and siRNA. Molecular precedents can be found for the design of hybrid compounds in the natural world, e.g., squalamine, the first representative of a previously unknown class of natural antibiotics of animal origin. These polyamine-bile acid (e.g. cholic acid type) conjugates display many exciting biological activities with the bile acids acting as a lipidic region and spermidine as the polycationic region. Analogues of squalamine can act as vectors in NVGT. Their natural role is as antibiotics. Novel antibacterial materials are urgently needed as recalcitrant bacterial infection is a worldwide problem for human health. Ribosome inhibitors founded upon dimers of tobramycin or neomycin, bound as ethers by a 1,6-hexyl linker or a more complex diether-disulfide linker, improved upon the antibiotic activity of aminoglycoside monomers by 20- to 1200-fold. Other hybrids, linked by click chemistry, conjugated ciprofloxacin to neomycin, trimethoprim, or tedizolid, which is now in clinical trials.

DOI: https://doi.org/10.1039/d2ra03281c
Am J Hum Genet. 2022 Jul 14. pii: S0002-9297(22)00263-4. [Epub ahead of print]

Bi-allelic variants in DOHH, catalyzing the last step of hypusine biosynthesis, are associated with a neurodevelopmental disorder.

Alban Ziegler, Katharina Steindl, Ashleigh S Hanner, Rajesh Kumar Kar, Clément Prouteau, Anne Boland, Jean Francois Deleuze, Christine Coubes, Stéphane Bézieau, Sébastien Küry, Isabelle Maystadt, Morgane Le Mao, Guy Lenaers, Benjamin Navet, Laurence Faivre, Frédéric Tran Mau-Them, Paolo Zanoni, Wendy K Chung, Anita Rauch, Dominique Bonneau, Myung Hee Park.

  Deoxyhypusine hydroxylase (DOHH) is the enzyme catalyzing the second step in the post-translational synthesis of hypusine [Nε-(4-amino-2-hydroxybutyl)lysine] in the eukaryotic initiation factor 5A (eIF5A). Hypusine is formed exclusively in eIF5A by two sequential enzymatic steps catalyzed by deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase (DOHH). Hypusinated eIF5A is essential for translation and cell proliferation in eukaryotes, and all three genes encoding eIF5A, DHPS, and DOHH are highly conserved throughout eukaryotes. Pathogenic variants affecting either DHPS or EIF5A have been previously associated with neurodevelopmental disorders. Using trio exome sequencing, we identified rare bi-allelic pathogenic missense and truncating DOHH variants segregating with disease in five affected individuals from four unrelated families. The DOHH variants are associated with a neurodevelopmental phenotype that is similar to phenotypes caused by DHPS or EIF5A variants and includes global developmental delay, intellectual disability, facial dysmorphism, and microcephaly. A two-dimensional gel analyses revealed the accumulation of deoxyhypusine-containing eIF5A [eIF5A(Dhp)] and a reduction in the hypusinated eIF5A in fibroblasts derived from affected individuals, providing biochemical evidence for deficiency of DOHH activity in cells carrying the bi-allelic DOHH variants. Our data suggest that rare bi-allelic variants in DOHH result in reduced enzyme activity, limit the hypusination of eIF5A, and thereby lead to a neurodevelopmental disorder.

Keywords:  DHPS; DOHH; EIF5A1; deoxyhypusine hydroxylase; eIF5A; hypusine; microcephaly; neurodevelopmental disorder; post-translational modification; translation

DOI:  https://doi.org/10.1016/j.ajhg.2022.06.010
Eur J Med Chem. 2022 Jul 09. pii: S0223-5234(22)00502-5. [Epub ahead of print]240 114600

The untapped potential of spermidine alkaloids: Sources, structures, bioactivities and syntheses.

Yan-Jing Shi, Jia Zhang, Yu-Wei Wang, Kang Ding, Yu Yan, Cong-Yuan Xia, Xin-Xin Li, Jun He, Wei-Ku Zhang, Jie-Kun Xu.

  Spermidine alkaloids are a kind of natural products possessing an aliphatic triamine structure with three or four methylene groups between two N-atoms. Spermidine alkaloids exist in plants, microorganisms, and marine organisms, which usually form amide structures with cinnamic acid or fatty acid derivatives. Their unique structures showed a wide range of biological activities such as neuroprotective, anti-aging, anti-cancer, antioxidant, anti-inflammatory, and antimicrobial. In order to better understand the research status of spermidine alkaloids and promote their applications in human health, this paper systematically reviewed the biological sources, structures, pharmacological actions, and synthetic processes of spermidine alkaloids over the past two decades. This will help to open up new pharmacological investigation fields and better drug design based on these spermidine alkaloids.

Keywords:  Biological activities; Natural occurrences; Spermidine alkaloids; Structural diversities; Syntheses

DOI:  https://doi.org/10.1016/j.ejmech.2022.114600
J Gen Appl Microbiol. 2022 Jul 21.

Influence of polyamine production and proteolytic activities of co-cultivated bacteria on histamine production by Morganiella morganii.

Suma Devivilla, Manjusha Lekshmi, Fathima Salam, Sanath Kumar H, Rajendran Kooloth Valappil, Sibnarayan Dam Roy, Binaya Bhusan Nayak.

  Consumption of temperature-abused marine fish containing elevated levels of histamine results in histamine poisoning. Histamine is a biogenic amine produced in fish by the action of certain groups of bacteria which are capable of producing an exogenous enzyme called histidine decarboxylase (HDC). Morganella morganii is one of the major causative organisms of histamine poisoning. In this study, the histamine forming potential of M. morganii (BSS142) is evaluated when it is co-incubated with proteolytic and polyamine forming bacteria. This experiment was designed to examine whether biotic factors such as proteolysis and the presence of other amines influenced histamine forming ability of BSS142. The study showed that the proteolytic activity of Aeromonas hydrophila as well as Pseudomonas aeruginosa greatly enhanced the histamine forming ability of M. morganii. Psychrobacter sangunis, a non proteolytic polyamine producer, negatively influenced histamine production by M. morganii.

Keywords:  Morganella morganii; biotic; hdc; histamine; polyamine; proteolytic

DOI:  https://doi.org/10.2323/jgam.2022.04.001