ArticlePloS one2014
The arginine decarboxylase pathways of host and pathogen interact to impact inflammatory pathways in the lung.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 29 citations in OpenAlex.
- Association between blood metabolites and chronic respiratory diseases: A Mendelian randomization study.Medicine · 2026Article
- Co-culture metabolomics: a powerful tool for uncovering host-pathogen phenotypes drivingmSystems · 2026Article
- Metabolomic profiling ofmSystems · 2025Article
- L-Arginine, as an essential amino acid, is a potential substitute for treating COPD via regulation of ROS/NLRP3/NF-κB signaling pathway.Cell & bioscience · 2023Article
- Article
- SP_0916 Is an Arginine Decarboxylase That Catalyzes the Synthesis of Agmatine, Which Is Critical for Capsule Biosynthesis inFrontiers in microbiology · 2020Article
- Agmatine accumulation by Pseudomonas aeruginosa clinical isolates confers antibiotic tolerance and dampens host inflammation.Journal of medical microbiology · 2019Article
- Article
- Structural and Functional Basis for Targeting Campylobacter jejuni Agmatine Deiminase To Overcome Antibiotic Resistance.Biochemistry · 2017Article
- Metabolic features of chronic fatigue syndrome.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Dual role of arginine metabolism in establishing pathogenesis.Current opinion in microbiology · 2016Review
- Determination of agmatine using isotope dilution UPLC-tandem mass spectrometry: application to the characterization of the arginine decarboxylase pathway in Pseudomonas aeruginosa.Analytical and bioanalytical chemistry · 2015Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
The arginine decarboxylase pathway, which converts arginine to agmatine, is present in both humans and most bacterial pathogens. In humans agmatine is a neurotransmitter with affinities towards α2-adrenoreceptors, serotonin receptors, and may inhibit nitric oxide synthase. In bacteria agmatine serves as a precursor to polyamine synthesis and was recently shown to enhance biofilm development in some strains of the respiratory pathogen Pseudomonas aeruginosa. We determined agmatine is at the center of a competing metabolism in the human lung during airways infections and is influenced by the metabolic phenotypes of the infecting pathogens. Ultra performance liquid chromatography with mass spectrometry detection was used to measure agmatine in human sputum samples from patients with cystic fibrosis, spent supernatant from clinical sputum isolates, and from bronchoalvelolar lavage fluid from mice infected with P. aeruginosa agmatine mutants. Agmatine in human sputum peaks during illness, decreased with treatment and is positively correlated with inflammatory cytokines. Analysis of the agmatine metabolic phenotype in clinical sputum isolates revealed most deplete agmatine when grown in its presence; however a minority appeared to generate large amounts of agmatine presumably driving sputum agmatine to high levels. Agmatine exposure to inflammatory cells and in mice demonstrated its role as a direct immune activator with effects on TNF-α production, likely through NF-κB activation. P. aeruginosa mutants for agmatine detection and metabolism were constructed and show the real-time evolution of host-derived agmatine in the airways during acute lung infection. These experiments also demonstrated pathogen agmatine production can upregulate the inflammatory response. As some clinical isolates have adapted to hypersecrete agmatine, these combined data would suggest agmatine is a novel target for immune modulation in the host-pathogen dynamic.
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Registered trials
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