ArticleScientific reports2018
Pyrimidine synthesis inhibition enhances cutaneous defenses against antibiotic resistant bacteria through activation of NOD2 signaling.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 22 citations in OpenAlex.
- Immune Roles of Canonically Non-Immune Cells in Biomaterials Response.Cell biomaterials · 2026Article
- Emerging host-directed strategies for overcoming drug resistance and immune evasion in Staphylococcus aureus infections.Journal of advanced research · 2026Review
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- Nucleotide Metabolic Reprogramming in Sepsis: From Immune-Cell Fate to Organ Injury and Precision Therapeutics.Journal of inflammation research · 2026Review
- Metabolic strategies that enable oral commensal persistence in a lower airway environment.mBio · 2025Article
- OMP38 of Carbapenem-Resistant Acinetobacter Baumannii-Mediated mtDNA Release Activates the cGAS-STING Signaling to Induce Inflammatory Response.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Identification of kinase modulators as host-directed therapeutics against intracellular methicillin-resistantFrontiers in cellular and infection microbiology · 2024Article
- Topical N-phosphonacetyl-l-aspartate is a dual action candidate for treating non-melanoma skin cancer.Experimental dermatology · 2023Article
- Impact of the pentose phosphate pathway on metabolism and pathogenesis of Staphylococcus aureus.PLoS pathogens · 2023Article
- A novel murine model of pyoderma gangrenosum reveals that inflammatory skin-gut crosstalk is mediated by IL-1β-primed neutrophils.Frontiers in immunology · 2023Article
- HIF-1 mediated activation of antimicrobial peptide LL-37 in type 2 diabetic patients.Journal of molecular medicine (Berlin, Germany) · 2022Article
- Pyrimidine Biosynthetic Enzyme CAD: Its Function, Regulation, and Diagnostic Potential.International journal of molecular sciences · 2021Review
- Article
- Host Innate Immune Responses toFrontiers in cellular and infection microbiology · 2020Review
- Pyrimidine biosynthesis in pathogens - Structures and analysis of dihydroorotases from Yersinia pestis and Vibrio cholerae.International journal of biological macromolecules · 2019Article
- Novel aroylated phenylenediamine compounds enhance antimicrobial defense and maintain airway epithelial barrier integrity.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multidrug-resistant bacterial strains are a rapidly emerging healthcare threat; therefore it is critical to develop new therapies to combat these organisms. Prior antibacterial strategies directly target pathogen growth or viability. Host-directed strategies to increase antimicrobial defenses may be an effective alternative to antibiotics and reduce development of resistant strains. In this study, we demonstrated the efficacy of a pyrimidine synthesis inhibitor, N-phosphonacetyl-L-aspartate (PALA), to enhance clearance of methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and Acinetobacter baumannii strains by primary human dermal fibroblasts in vitro. PALA did not have a direct bactericidal effect, but enhanced cellular secretion of the antimicrobial peptides human β-defensin 2 (HBD2) and HBD3 from fibroblasts. When tested in porcine and human skin explant models, a topical PALA formulation was efficacious to enhance MRSA, P. aeruginosa, and A. baumannii clearance. Topical PALA treatment of human skin explants also resulted in increased HBD2 and cathelicidin (LL-37) production. The antimicrobial actions of PALA required expression of nucleotide-binding, oligomerization domain 2 (NOD2), receptor-interacting serine/threonine-protein kinase 2 (RIP2), and carbamoyl phosphatase synthase II/aspartate transcarbamylase/dihydroorotase (CAD). Our results indicate that PALA may be a new option to combat multidrug-resistant bacterial infections of the skin through enhancement of an integral pathway of the cutaneous innate immune defense system.
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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.