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Pathogens
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Polyamines, Arginine and Pathogens: From Fundamental Biology to Host-Pathogen Dynamics
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Polyamines, Arginine and Pathogens: From Fundamental Biology to Host-Pathogen Dynamics

A special issue of Pathogens (ISSN 2076-0817).

Deadline for manuscript submissions: 15 September 2026 | Viewed by 2888

Editors

Prof. Dr. Sigrid C. Roberts

E-Mail Website
Guest Editor
School of Pharmacy, Pacific University, Hillsboro, OR, USA
Interests: the neglected tropical disease leishmaniasis
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Nicola Carter

E-Mail Website
Guest Editor
School of Pharmacy, Pacific University, Hillsboro, OR 97123, USA
Interests: molecular biology; cell biology; metabolism; host–pathogen interaction; Leishmania; Trypanosoma
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Arginine and its downstream metabolites, polyamines, are critical regulators of cellular function in both pathogens and their hosts. These molecules influence a wide array of biological processes, including metabolism, stress adaptation, immune modulation, and virulence. In infectious diseases, pathogens not only depend on polyamine metabolism for survival and proliferation but also manipulate host arginine and polyamine pathways to promote infection and evade immune defenses.

This Special Issue delves into the diverse and interconnected roles of arginine and polyamines in microbial physiology and host–pathogen interactions. Featuring research across bacterial, parasitic, and viral systems, it highlights recent discoveries in the fundamental biology of these pathways, their contributions to infection and immunity, and emerging strategies for therapeutic intervention. By bridging basic and translational science, this collection aims to foster a deeper understanding of arginine and polyamine biology in the context of infectious disease. We welcome authors to submit original research or review articles on topics including, but not limited to, the following themes:

  • Polyamines and stress adaptation in pathogens;
  • Comparative polyamine biology in bacterial, parasitic, and viral pathogens;
  • Systems biology, imaging, and genetic tools to investigate arginine and polyamine pathways in infection;
  • Host–pathogen competition for arginine and polyamine resources;
  • Mechanisms of immune modulation via arginine or polyamine pathways;
  • Crosstalk between host and microbial arginine/polyamine metabolism;
  • Enzymes and transporters regulating polyamine biosynthesis and uptake in pathogens;
  • Therapeutic targeting of arginine or polyamine metabolism in infectious diseases;
  • Emerging inhibitors of polyamine biosynthesis and/or transport.

Prof. Dr. Sigrid C. Roberts
Prof. Dr. Nicola Carter
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pathogens is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2400 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • pathogens
  • polyamines
  • polyamine metabolism
  • putrescine
  • spermidine
  • spermine
  • arginase
  • eiF5A
  • host–pathogen interactions
  • infectious diseases
  • bacteria
  • viruses
  • parasites

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Published Papers (3 papers)

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Research

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15 pages, 2676 KB  
Article
Functional and Biochemical Characterization of Spermidine Synthase CauSpe3 from Candidozyma auris
by Jae-Yeon Choi, Pallavi Singh and Choukri Ben Mamoun
Pathogens 2026, 15(4), 432; https://doi.org/10.3390/pathogens15040432 - 16 Apr 2026
Viewed by 614
Abstract
Polyamines, putrescine, spermidine and spermine, are essential polycationic metabolites present in all eukaryotic cells, where they regulate fundamental processes including nucleic acid stabilization, translation, and stress responses. Spermidine synthase (SPDS), a member of the aminopropyltransferase (APT) family, catalyzes the transfer of an aminopropyl [...] Read more.
Polyamines, putrescine, spermidine and spermine, are essential polycationic metabolites present in all eukaryotic cells, where they regulate fundamental processes including nucleic acid stabilization, translation, and stress responses. Spermidine synthase (SPDS), a member of the aminopropyltransferase (APT) family, catalyzes the transfer of an aminopropyl group from decarboxylated S-adenosylmethionine (dc-SAM) to putrescine to form spermidine. Although genomic analyses predict the presence of SPDS homologs in multiple fungal species, polyamine biosynthesis has not been experimentally characterized in the multidrug-resistant fungal pathogen Candidozyma auris. Here, we report the biochemical and functional characterization of the C. auris spermidine synthase, CauSpe3. The CauSPE3 gene complemented a Saccharomyces cerevisiae spe3Δ mutant demonstrating conserved function in vivo. Recombinant CauSpe3 was expressed in Escherichia coli, purified and analyzed using the fluorescence-based DAB-APT assay, which uses 1,2-diacetylbenzene (DAB) for polyamine detection. CauSpe3 catalyzed efficient conversion of putrescine to spermidine in the presence of dc-SAM, with Khalf values of 65.5 ± 7.11 µM for putrescine and 66.9 ± 2.09 µM for dc-SAM, and Vmax values of 7.1 ± 0.57 and 7.9 ± 0.12 nmol·µg−1·min−1, respectively. A catalytic-site mutant and heat-inactivated enzyme showed no detectable activity, and product formation was confirmed by means of thin-layer chromatography and mass spectrometry. These findings establish CauSpe3 as a functional spermidine synthase. Full article
(This article belongs to the Special Issue Polyamines, Arginine and Pathogens: From Fundamental Biology to Host-Pathogen Dynamics)
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Review

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16 pages, 2660 KB  
Review
Dual Functions of Polyamines in Shaping Host-Specific Pathogen Dynamics
by Xolani H. Makhoba
Pathogens 2026, 15(7), 695; https://doi.org/10.3390/pathogens15070695 - 30 Jun 2026
Viewed by 454
Abstract
Polyamines such as putrescine, spermidine, and spermine play essential roles in most living organisms. They regulate fundamental processes, like cell proliferation, differentiation, growth, gene expression (DNA/RNA stability, transcription, and translation), and signal transduction. As important regulators, polyamines influence development, stress responses, and the [...] Read more.
Polyamines such as putrescine, spermidine, and spermine play essential roles in most living organisms. They regulate fundamental processes, like cell proliferation, differentiation, growth, gene expression (DNA/RNA stability, transcription, and translation), and signal transduction. As important regulators, polyamines influence development, stress responses, and the progression of health and disease, including cancer and aging. These positively charged molecules have been extensively studied for decades. In humans, polyamines are often researched as potential therapeutic targets for diseases such as malaria and, more recently, COVID-19. Obligate parasites, such as Plasmodium falciparum, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rely on host cellular machinery for survival, replication, and growth. Notably, both hosts and pathogens need polyamines to sustain these processes. This review summarizes current advances in understanding the roles of polyamines in humans, viruses, and obligate parasites. It also explores strategies to prevent pathogens from hijacking host polyamine metabolism as a way toward developing novel therapeutic interventions. Full article
(This article belongs to the Special Issue Polyamines, Arginine and Pathogens: From Fundamental Biology to Host-Pathogen Dynamics)
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25 pages, 1805 KB  
Review
Polyamines as Gatekeepers of Virus Replication and Central Nervous System Homeostasis
by Samantha P. Stacey and Bryan C. Mounce
Pathogens 2026, 15(4), 422; https://doi.org/10.3390/pathogens15040422 - 14 Apr 2026
Viewed by 1030
Abstract
Polyamines are small, positively charged molecules essential for fundamental cellular processes, including transcription, translation, and membrane fluidity. In the central nervous system (CNS), these molecules serve as homeostatic gatekeepers by modulating neuroreceptors like NMDA and supporting autophagic clearance. While basal polyamine levels are [...] Read more.
Polyamines are small, positively charged molecules essential for fundamental cellular processes, including transcription, translation, and membrane fluidity. In the central nervous system (CNS), these molecules serve as homeostatic gatekeepers by modulating neuroreceptors like NMDA and supporting autophagic clearance. While basal polyamine levels are necessary for proper neuronal differentiation and memory formation, their dysregulation is a hallmark of neurodegenerative pathologies such as Alzheimer’s and Parkinson’s diseases. Neurotropic viruses, including poliovirus, Zika virus, and human cytomegalovirus are significant human pathogens that rely on cellular metabolites for their replication, including polyamines. These pathogens exploit polyamines at multiple stages of their life cycles, relying on them for virion stability, cellular attachment, and the stimulation of viral enzyme activity. Notably, diverse viral families share this dependence, making polyamine biosynthesis a prime target for broad-spectrum antiviral therapies. This review covers the current understanding of polyamine metabolism in virus infection and CNS health and disease, as well as considering antiviral therapies targeting host polyamines to limit neurotropic virus infection. Full article
(This article belongs to the Special Issue Polyamines, Arginine and Pathogens: From Fundamental Biology to Host-Pathogen Dynamics)
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