bims-polyam 2022-06-05 papers

Issue of 2022–06–05
six papers selected by
Sebastian J. Hofer, University of Graz

Med Sci (Basel). 2022 Apr 22. pii: 24. [Epub ahead of print]10(2):

Polyamine Metabolism in Leishmania Parasites: A Promising Therapeutic Target.

Nicola S Carter, Yumena Kawasaki, Surbhi S Nahata, Samira Elikaee, Sara Rajab, Leena Salam, Mohammed Y Alabdulal, Kelli K Broessel, Forogh Foroghi, Alyaa Abbas, Reyhaneh Poormohamadian, Sigrid C Roberts.

Parasites of the genus Leishmania cause a variety of devastating and often fatal diseases in humans and domestic animals worldwide. The need for new therapeutic strategies is urgent because no vaccine is available, and treatment options are limited due to a lack of specificity and the emergence of drug resistance. Polyamines are metabolites that play a central role in rapidly proliferating cells, and recent studies have highlighted their critical nature in Leishmania. Numerous studies using a variety of inhibitors as well as gene deletion mutants have elucidated the pathway and routes of transport, revealing unique aspects of polyamine metabolism in Leishmania parasites. These studies have also shed light on the significance of polyamines for parasite proliferation, infectivity, and host-parasite interactions. This comprehensive review article focuses on the main polyamine biosynthetic enzymes: ornithine decarboxylase, S-adenosylmethionine decarboxylase, and spermidine synthase, and it emphasizes recent discoveries that advance these enzymes as potential therapeutic targets against Leishmania parasites.

Keywords: Leishmania; S-adenosylmethionine decarboxylase; drug resistance; ornithine decarboxylase; polyamines; putrescine; spermidine; spermidine synthase; transport

DOI: https://doi.org/10.3390/medsci10020024

Biosci Biotechnol Biochem. 2022 Jun 01. pii: zbac080. [Epub ahead of print]

Polyamine metabolism and transport in gut microbes.

Shin Kurihara.

Polyamines (putrescine, spermidine, and spermine) are compounds with amino groups at both ends of a hydrocarbon. Polyamines produced by intestinal bacteria suppress chronic inflammation and enhance the intestinal barrier in the colon, and are also transferred into the blood via the colonic epithelium, resulting in significant improvement of host cognitive performance and life extension in mice. Upregulation of polyamine production by gut microbes can help compensate for aging-associated decrease in polyamine content through the uptake of intestinal luminal polyamine, thereby extending healthy life expectancy of the host. This review summarizes recent advances in the study of polyamine metabolism and transport in gut microbes, with particular reference to Escherichia coli and the most predominant species of the gut microbiota. Furthermore, we describe polyamine production by a novel hybrid system comprised of multiple gut microbes, as well as from high-polyamine-producing lactic acid bacteria derived from fermented foods.

Keywords: Gut microbes; Polyamine biosynthesis; Polyamine transport; hybrid metabolic pathway; γ-glutamylation

DOI: https://doi.org/10.1093/bbb/zbac080

J Biochem. 2022 May 25. pii: mvac048. [Epub ahead of print]

Polyamines produced by an extreme thermophile are essential for cell growth at high temperature.

Akihiko Sakamoto, Masatada Tamakoshi, Toshiyuki Moriya, Tairo Oshima, Koichi Takao, Yoshiaki Sugita, Takemitsu Furuchi, Masaru Niitsu, Takeshi Uemura, Kazuei Igarashi, Keiko Kashiwagi, Yusuke Terui.

An extreme thermophile, Thermus thermophilus grows at an optimum temperature of around 70 oC and produces 16 different polyamines including long-chain and branched-chain polyamines. We found that the composition of polyamines in the thermophile cells changes with culture temperature. Long-chain and branched-chain polyamines (unusual polyamines) were increased in the cells grown at high temperature such as 80 oC, but they were minor components in the cells grown at relatively lower temperature such as 60 oC. The effects of polyamines on cell growth were studied using T. thermophilus HB8 ΔspeA deficient in arginine decarboxylase. Cell growth of this mutant strain was significantly decreased at 70 oC. This mutant strain cannot produce polyamines and grows poorly at 75 oC. It was also determined whether polyamines are directly involved in protecting DNA from DNA double-strand breaks induced by heat. Polyamines protected DNA against double-strand breaks. Therefore, polyamines play essential roles in cell growth at extremely high temperature through maintaining a functional conformation of DNA against DNA double-strand breaks and depurination.

Keywords: DNA double-strand breaks; Thermus thermophilus; cell growth; high temperature; polyamine

DOI: https://doi.org/10.1093/jb/mvac048

Front Cell Dev Biol. 2022 ;10 819571

Investigating the Role of Spermidine in a Model System of Alzheimer's Disease Using Correlative Microscopy and Super-resolution Techniques.

D Lumkwana, C Peddie, J Kriel, L L Michie, N Heathcote, L Collinson, C Kinnear, B Loos.

Background: Spermidine has recently received major attention for its potential therapeutic benefits in the context of neurodegeneration, cancer, and aging. However, it is unclear whether concentration dependencies of spermidine exist, to differentially enhance autophagic flux. Moreover, the relationship between low or high autophagy activity relative to basal neuronal autophagy flux and subsequent protein clearance as well as cellular toxicity has remained largely unclear. Methods: Here, we used high-resolution imaging and biochemical techniques to investigate the effects of a low and of a high concentration of spermidine on autophagic flux, neuronal toxicity, and protein clearance in in vitro models of paraquat (PQ) induced neuronal toxicity and amyloid precursor protein (APP) overexpression, as well as in an in vivo model of PQ-induced rodent brain injury. Results: Our results reveal that spermidine induces autophagic flux in a concentration-dependent manner, however the detectable change in the autophagy response critically depends on the specificity and sensitivity of the method employed. By using correlative imaging techniques through Super-Resolution Structured Illumination Microscopy (SR-SIM) and Focused Ion Beam Scanning Electron Microscopy (FIB-SEM), we demonstrate that spermidine at a low concentration induces autophagosome formation capable of large volume clearance. In addition, we provide evidence of distinct, context-dependent protective roles of spermidine in models of Alzheimer's disease. In an in vitro environment, a low concentration of spermidine protected against PQ-induced toxicity, while both low and high concentrations provided protection against cytotoxicity induced by APP overexpression. In the in vivo scenario, we demonstrate brain region-specific susceptibility to PQ-induced neuronal toxicity, with the hippocampus being highly susceptible compared to the cortex. Regardless of this, spermidine administered at both low and high dosages protected against paraquat-induced toxicity. Conclusions: Taken together, our results demonstrate that firstly, administration of spermidine may present a favourable therapeutic strategy for the treatment of Alzheimer's disease and secondly, that concentration and dosage-dependent precision autophagy flux screening may be more critical for optimal autophagy and cell death control than previously thought.

Keywords: Alzheimer’s disease; autophagy; correlative light and electron microscopy; direct stochastic optical reconstruction microscopy; focused ion beam scanning electron microscopy; spermidine; super-resolution structured illumination

DOI: https://doi.org/10.3389/fcell.2022.819571

World J Microbiol Biotechnol. 2022 Jun 01. 38(7): 124

The effect of polyamines and silver thiosulphate on micropropagation of date palm followed by genetic stability assessment.

Ahmed Madi Waheed Al-Mayahi.

There are some limitations in date palm micropropagation. These include low multiplication efficiency, low rooting rate, and high mortality experienced by in vitro raised plantlets during laboratory to soil transfer. The objective of the study was to determine the effect of the polyamines and Silver Thiosulphate (STS) on the enhancement of shoot multiplication and genetic stability of in vitro cultures of date palm cultivar Quntar. Media supplemented with 75 mg L-1 SPD in combination with 10 mg L-1 STS gave the highest percentage of callus producing buds (83.34%) and average bud formation (16.3) per jar. The addition of PUT and STS to the medium was most effective on root formation and the number of roots per shoot, where the best result, 91.67% and 6.37 roots per shoot, respectively, were obtained using 75 mg L-1 PUT and 10 mg L-1 STS, resulting in fast-growing plantlets during acclimatization phase, reaching 80% of plant survival. The genetic fidelity assessment of plants derived from micropropagation was confirmed by RAPD analysis. Four operon primers were used, and all of them showed amplified unambiguous (OPA02, OPC-04, OPD-07, and OPE-15). All generated bands were monomorphic and had no variation among the tissue culture-derived plants tested. Accordingly, these results indicate that adding polyamines and silver thiosulfate to the nutrient medium of date palm cv. Quntar was beneficial to improving shoot organogenesis, rooting, and production of genetically stable date palm plants.

Keywords: Acclimatization; Multiplication; RAPD; Rooting; Shoot regeneration

DOI: https://doi.org/10.1007/s11274-022-03305-5

Curr Opin Pharmacol. 2022 May 29. pii: S1471-4892(22)00065-0. [Epub ahead of print]65 102238

Metabolomics of airways disease in cystic fibrosis.

Joshua D Chandler, Charles R Esther.

While discovery metabolomic studies have identified many potential biomarkers of cystic fibrosis (CF) airways disease, relatively few have been validated. We review the recent literature to identify the most promising metabolomic findings as those repeatedly observed over multiple studies. Reproducible metabolomic findings include increased airway amino acids and small peptides in CF airways, as well as changes in phospholipids and sphingolipids. Other commonly altered pathways include adenosine metabolism, polyamine synthesis, and oxidative stress. These pathways represent potential biomarkers and therapeutic targets, though findings require reevaluation in the era of highly effective modulator therapies. Analysis of airway biomarkers in exhaled breath holds promise for non-invasive detection, though technical challenges will need to be overcome.

DOI: https://doi.org/10.1016/j.coph.2022.102238