ArticleMicrobiome2019
Neutrophilic proteolysis in the cystic fibrosis lung correlates with a pathogenic microbiome.
Article in Microbiome, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- Potential Association Between Changes in Microbiota Level and Lung Diseases: A Meta-Analysis.Frontiers in medicine · 2021Pooled it
- The role of the respiratory microbiome in acute and chronic respiratory diseases.Nature reviews. Microbiology · 2026Review
- Mitochondria Meet the Lung Microbiome: A Bidirectional Dialogue in Inflammation and Respiratory Diseases.Biomedicines · 2026Review
- Dynamic balance of the lung microbiome in health and respiratory diseases.Chinese medical journal · 2026Review
- Cathepsin B, Airway Pathogens, and Inflammation in the Lower Airways of Children With Cystic Fibrosis.Pediatric pulmonology · 2026Article
- Differential Metabolite Production Underlies Disruption of the Cystic Fibrosis Airway Microbiota by Pathogens.bioRxiv : the preprint server for biology · 2026Article
- Article
- Microenvironmental effects of a non-antibiotic therapy for a chronic Polymicrobial infection Alter microbial physiology, competition, and virulence.The ISME journal · 2026Article
- People with cystic fibrosis with high sputum neutrophil elastase on elexacaftor-tezacaftor-ivacaftor exhibit worse pulmonary function and pro-inflammatory airway milieu.Scientific reports · 2025Article
- Therapeutic Inhibition of Metalloproteases by Tetracyclines During Infection by Multidrug-Resistant Pseudomonas.The Journal of infectious diseases · 2025Article
- Article
- Microbiome and metabolome patterns after lung transplantation reflect underlying disease and chronic lung allograft dysfunction.Microbiome · 2024Article
- Neutrophil-Derived Proteases in Lung Inflammation: Old Players and New Prospects.International journal of molecular sciences · 2024Review
- Integrated annotation prioritizes metabolites with bioactivity in inflammatory bowel disease.Molecular systems biology · 2024Article
- A GMR enzymatic assay for quantifying nuclease and peptidase activity.Frontiers in bioengineering and biotechnology · 2024Article
- Longitudinal microbial and molecular dynamics in the cystic fibrosis lung after Elexacaftor-Tezacaftor-Ivacaftor therapy.Respiratory research · 2023Article
- Effect of seven anti-tuberculosis treatment regimens on sputum microbiome: a retrospective analysis of the HIGHRIF study 2 and PanACEA MAMS-TB clinical trials.The Lancet. Microbe · 2023Article
- Longitudinal Microbial and Molecular Dynamics in the Cystic Fibrosis Lung after Elexacaftor-Tezacaftor-Ivacaftor therapy.Research square · 2023Article
- Multiomic Investigations into Lung Health and Disease.Microorganisms · 2023Review
- Metabolomics identifies disturbances in arginine, phenylalanine, and glycine metabolism as differentiating features of exacerbating atopic asthma in children.The journal of allergy and clinical immunology. Global · 2023Article
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundStudies of the cystic fibrosis (CF) lung microbiome have consistently shown that lung function decline is associated with decreased microbial diversity due to the dominance of opportunistic pathogens. However, how this phenomenon is reflected in the metabolites and chemical environment of lung secretions remains poorly understood.
methodsHere we investigated the microbial and molecular composition of CF sputum samples using 16S rRNA gene amplicon sequencing and untargeted tandem mass spectrometry to determine their interrelationships and associations with clinical measures of disease severity.
resultsThe CF metabolome was found to exist in two states: one from patients with more severe disease that had higher molecular diversity and more Pseudomonas aeruginosa and the other from patients with better lung function having lower metabolite diversity and fewer pathogenic bacteria. The two molecular states were differentiated by the abundance and diversity of peptides and amino acids. Patients with severe disease and more pathogenic bacteria had higher levels of peptides. Analysis of the carboxyl terminal residues of these peptides indicated that neutrophil elastase and cathepsin G were responsible for their generation, and accordingly, these patients had higher levels of proteolytic activity from these enzymes in their sputum. The CF pathogen Pseudomonas aeruginosa was correlated with the abundance of amino acids and is known to primarily feed on them in the lung.
conclusionsIn cases of severe CF lung disease, proteolysis by host enzymes creates an amino acid-rich environment that P. aeruginosa comes to dominate, which may contribute to the pathogen's persistence by providing its preferred carbon source.
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