bims-polyam 2020-09-27 papers

ACS Infect Dis. 2020 Sep 23.

Targeting polyamines inhibits coronavirus infection by reducing cellular attachment.

Mason R Firpo, Vincent Mastrodomenico, Grant Hawkins, Matthieu Prot, Laura Levillayer, Thomas Gallagher, Etienne Simon-Loriere, Bryan Mounce.

Coronaviruses first garnered widespread attention in 2002 when the severe acute respiratory syndrome coronavirus (SARS-CoV) emerged from bats in China and rapidly spread in human populations. Since then, Middle East respiratory syndrome virus (MERS-CoV) emerged and still actively infects humans. The recent SARS-CoV-2 outbreak and the resulting disease (coronavirus disease 2019 - COVID19) have rapidly and catastrophically spread and highlighted significant limitations to our ability to control and treat infection. Thus, antivirals targeting coronavirus infection are urgently needed to reduce the severe burden on our health systems and to protect vulnerable populations. Here, we show that polyamines, small metabolites synthesized in human cells, facilitate coronavirus replication, and depletion of polyamines with FDA-approved molecules significantly reduces coronavirus replication. We find that polyamines facilitate viral attachment to susceptible cells and that diverse coronaviruses, including endemic and epidemic coronaviruses, exhibit reduced attachment to polyamine-depleted cells. We further demonstrate that several molecules targeting the polyamine biosynthetic pathway are antiviral. In sum, our data suggest that polyamines are critical to coronavirus entry and represent a highly promising drug target in the current and any future coronavirus outbreaks.

DOI: https://doi.org/10.1021/acsinfecdis.0c00491

Mol Oral Microbiol. 2020 Sep 26.

Polyamines in the Virulence of Bacterial Pathogens of Respiratory Tract.

Rajashri Banerji, Poonam Kanojiya, Amrita Patil, Sunil D Saroj.

Polyamines are positively charged hydrocarbons that are essential for the growth and cellular maintenance in prokaryotes and eukaryotes. Polyamines have been demonstrated to play a role in bacterial pathogenicity and biofilm formation. However, the role of extracellular polyamines as a signaling molecule in the regulation of virulence is not investigated in detail. The bacterial pathogens residing in the respiratory tract remains asymptomatic for an extended period; however, the factors that lead to symptomatic behavior is poorly understood. Further investigation to understand the relation between the host-secreted factors and virulence of pathogenic bacteria in the respiratory tract may provide insights into the pathogenesis of respiratory tract infections. Polyamines produced within the bacterial cell are generally sequestered. Therefore, the pool of extracellular polyamines formed by secretion of the commensals and the host may be one of the signaling molecules that might contribute towards the alterations in the expression of virulence factors in bacterial pathogens. Besides, convergent mechanisms of polyamine biosynthesis do exist across the border of species and genus level. Also, several novel polyamine transporters in the host and bacteria remain yet to be identified. The review focusses on the role of polyamines in the expression of virulence phenotypes and biofilm formation of the respiratory tract pathogens.

Keywords: antimicrobial resistance; biofilm formation; pathogens; respiratory tract infections; stress response; virulence

DOI: https://doi.org/10.1111/omi.12315

Analyst. 2020 Sep 24.

A gas pressure and colorimetric signal dual-mode strategy for sensitive detection of spermine using ssDNA-coated Au@Pt nanoparticles as the probe.

Huan Jiang, Xinyue Rao, Ling Li, Zhongde Liu.

The naturally occurring spermine (Spm), as one of the many cationic polyamines, plays a key role in biological processes and is involved in a variety of diseases. The very similar structures among biogenic polyamines present a major challenge to achieve discriminative testing among them. In this contribution, using arbitrary ssDNA-coated Au@PtNPs as the probe, we demonstrated that a dual-mode strategy via a gas pressure and colorimetric signal readout can be used for the sensitive and specific detection of Spm, due to the target-responsive aggregation of the Au@PtNPs leading to the inhibition of the catalyzed gas-generation reaction and the colorimetric change of the Au@PtNP solution. The proposed pressure-based signaling strategy has a detection limit of 9.6 nM, and can be used not only in the laboratory but also in the point-of-care setting. Meanwhile, the colorimetric assay displays the advantage of being easily discerned with the naked eye. Compared with the traditional methods of chromatography and capillary electrophoresis combined with chemical derivatization, the strategy described here would provide a convenient new alternative for the specific detection of Spm in biological samples.

DOI: https://doi.org/10.1039/d0an01473g

Biogerontology. 2020 Sep 26.

Spermidine, a caloric restriction mimetic, provides neuroprotection against normal and D-galactose-induced oxidative stress and apoptosis through activation of autophagy in male rats during aging.

Sandeep Singh, Raushan Kumar, Geetika Garg, Abhishek Kumar Singh, Avnish Kumar Verma, Akalabya Bissoyi, Syed Ibrahim Rizvi.

Spermidine (SPD) is a natural polyamine present in all living organisms and is involved in the maintenance of cellular homeostasis by inducing autophagy in different model organisms. Its role as a caloric restriction mimetic (CRM) is still being investigated. We have undertaken this study to investigate whether SPD, acting as a CRM, can confer neuroprotection in D-galactose induced accelerated senescence model rat and naturally aged rats through modulation of autophagy and inflammation. Young male rats (4 months), D-gal induced (500 mg/kg b.w., subcutaneously) aging and naturally aged (22 months) male rats were supplemented with SPD (10 mg/kg b.w., orally) for 6 weeks. Standard protocols were employed to measure prooxidants, antioxidants, apoptotic cell death and electron transport chain complexes in brain tissues. Gene expression analysis with reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to assess the expression of autophagy and inflammatory marker genes. Our data demonstrate that SPD significantly (p ≤ 0.05) decreased the level of pro-oxidants and increased the level of antioxidants. SPD supplementation also augmented the activities of electron transport chain complexes in aged brain mitochondria thus proving its antioxidant potential at the level of mitochondria. RT-PCR data revealed that SPD up-regulated the expression of autophagy genes (ATG-3, Beclin-1, ULK-1 and LC3B) and down-regulated the expression of the inflammatory gene (IL-6) in aging brain. Our results provide first line of evidence that SPD provides neuroprotection against aging-induced oxidative stress by regulating autophagy, antioxidants level and also reduces neuroinflammation. These results suggest that SPD may be beneficial for neuroprotection during aging and age-related disorders.

Keywords: Aging; Apoptosis; Autophagy; Caloric restriction mimetics; Spermidine

DOI: https://doi.org/10.1007/s10522-020-09900-z

Elife. 2020 Sep 22. pii: e55744. [Epub ahead of print]9

Host-induced spermidine production in motile Pseudomonas aeruginosa triggers phagocytic uptake.

Sebastian Felgner, Matthias Preusse, Ulrike Beutling, Stephanie Stahnke, Vinay Pawar, Manfred Rohde, Mark Brönstrup, Theresia Stradal, Susanne Häussler.

Exploring the complexity of host-pathogen communication is vital to understand why<br /> microbes persist within a host, while others are cleared. Here, we employed a Dual-sequencing approach to unravel conversational turn-taking of dynamic host-pathogen communications. We demonstrate that upon hitting a host cell, motile Pseudomonas aeruginosa induce a specific gene expression program. This results in the expression of spermidine on the surface, which specifically activates the PIP3-pathway to induce phagocytic uptake into primary or immortalized murine cells. Non-motile bacteria are more immunogenic due to a lower expression of arnT upon host cell contact, but do not produce spermidine and are phagocytosed less. We demonstrate that not only the presence of pathogen inherent molecular patterns induces immune responses, but that bacterial motility is linked to a host-cell induced expression of additional immune modulators. Our results emphasize on the value of integrating microbiological and immunological findings to unravel complex and dynamic host-pathogen interactions.

Keywords: infectious disease; microbiology

DOI: https://doi.org/10.7554/eLife.55744

Nat Metab. 2020 Sep 24.

Publisher Correction: The smell of death and deCYStiny: polyamines play the hero.

Joseph A Combs, Gina M DeNicola.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

DOI: https://doi.org/10.1038/s42255-020-00303-5