ArticleProceedings of the National Academy of Sciences of the United States of America2015
Disulphide-reduced psoriasin is a human apoptosis-inducing broad-spectrum fungicide.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
43 citing papers in PubMed, 77 citations in OpenAlex.
- Formation of the intradimer disulfide bond in human calprotectin maintains metal-withholding function and tunes proteolytic susceptibility.Chemical science · 2026Article
- The Contribution of Human Antimicrobial Peptides to Fungi.International journal of molecular sciences · 2025Review
- Antifungal recombinant psoriasin of human origin effectively inhibits fungal growth on denture base.Oral diseases · 2025Article
- Therapeutic potential of mesenchymal stem cells for fungal infections: mechanisms, applications, and challenges.Frontiers in microbiology · 2025Review
- A novel zinc-chelating compound has antifungal activity against a wide range ofJAC-antimicrobial resistance · 2024Article
- Zinc Starvation Induces Cell Wall Remodeling and Activates the Antioxidant Defense System inJournal of fungi (Basel, Switzerland) · 2024Article
- Exploring the frontiers of therapeutic breadth of antifungal peptides: A new avenue in antifungal drugs.Journal of industrial microbiology & biotechnology · 2024Review
- Diabetes downregulates the antimicrobial peptide psoriasin and increases E. coli burden in the urinary bladder.Nature communications · 2022Article
- Antimicrobial Peptides with Anti-International journal of molecular sciences · 2022Review
- Metal sequestration by S100 proteins in chemically diverse environments.Trends in microbiology · 2022Review
- Selective Metal Chelation by a Thiosemicarbazone Derivative Interferes with Mitochondrial Respiration and Ribosome Biogenesis in Candida albicans.Microbiology spectrum · 2022Article
- Mechanical control of innate immune responses against viral infection revealed in a human lung alveolus chip.Nature communications · 2022Article
- Adherence Enables Neisseria gonorrhoeae to Overcome Zinc Limitation Imposed by Nutritional Immunity Proteins.Infection and immunity · 2022Article
- At the metal-metabolite interface inMicrobiology (Reading, England) · 2021Article
- Nutritional immunity: targeting fungal zinc homeostasis.Heliyon · 2021Review
- Redox Active Antimicrobial Peptides in Controlling Growth of Microorganisms at Body Barriers.Antioxidants (Basel, Switzerland) · 2021Review
- Leveraging orthogonal mass spectrometry based strategies for comprehensive sequencing and characterization of ribosomal antimicrobial peptide natural products.Natural product reports · 2021Review
- Antimicrobial Peptides in Farm Animals: An Updated Review on Its Diversity, Function, Modes of Action and Therapeutic Prospects.Veterinary sciences · 2020Review
- Review
- Synthesis, Docking, Computational Studies, and Antimicrobial Evaluations of New Dipeptide Derivatives Based on Nicotinoylglycylglycine Hydrazide.Molecules (Basel, Switzerland) · 2020Article
Corrections and comments
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Authors and funding
13 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The unexpected resistance of psoriasis lesions to fungal infections suggests local production of an antifungal factor. We purified Trichophyton rubrum-inhibiting activity from lesional psoriasis scale extracts and identified the Cys-reduced form of S100A7/psoriasin (redS100A7) as a principal antifungal factor. redS100A7 inhibits various filamentous fungi, including the mold Aspergillus fumigatus, but not Candida albicans. Antifungal activity was inhibited by Zn(2+), suggesting that redS100A7 interferes with fungal zinc homeostasis. Because S100A7-mutants lacking a single cysteine are no longer antifungals, we hypothesized that redS100A7 is acting as a Zn(2+)-chelator. Immunogold electron microscopy studies revealed that it penetrates fungal cells, implicating possible intracellular actions. In support with our hypothesis, the cell-penetrating Zn(2+)-chelator TPEN was found to function as a broad-spectrum antifungal. Ultrastructural analyses of redS100A7-treated T. rubrum revealed marked signs of apoptosis, suggesting that its mode of action is induction of programmed cell death. TUNEL, SYTOX-green analyses, and caspase-inhibition studies supported this for both T. rubrum and A. fumigatus. Whereas redS100A7 can be generated from oxidized S100A7 by action of thioredoxin or glutathione, elevated redS100A7 levels in fungal skin infection indicate induction of both S100A7 and its reducing agent in vivo. To investigate whether redS100A7 and TPEN are antifungals in vivo, we used a guinea pig tinea pedes model for fungal skin infections and a lethal mouse Aspergillus infection model for lung infection and found antifungal activity in both in vivo animal systems. Thus, selective fungal cell-penetrating Zn(2+)-chelators could be useful as an urgently needed novel antifungal therapeutic, which induces programmed cell death in numerous fungi.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.