Evidence map›Paper›PMID 30760325›Full record

ArticleMicrobiome2019

Neutrophilic proteolysis in the cystic fibrosis lung correlates with a pathogenic microbiome.

Robert A Quinn, Sandeep Adem, Robert H Mills, William Comstock, Lindsay DeRight Goldasich, Gregory Humphrey, Alexander A Aksenov, Alexei V Melnik, Ricardo da Silva, Gail Ackermann and 6 more

Open access · goldAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed, 1 pooled it
7.3field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

48 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.

  1. Pooled it
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  5. Article
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  7. Journal of bacteriology · 2026
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  15. A GMR enzymatic assay for quantifying nuclease and peptidase activity.Frontiers in bioengineering and biotechnology · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 2 institutions in 1 country.

Robert A QuinnSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
Sandeep AdemSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
Robert H MillsSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
William ComstockSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
Lindsay DeRight GoldasichDepartment of Pediatrics, University of California San Diego, La Jolla, CA, USA.
Gregory HumphreyDepartment of Pediatrics, University of California San Diego, La Jolla, CA, USA.
Alexander A AksenovSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
Alexei V MelnikSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
Ricardo da SilvaSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
Gail AckermannDepartment of Pediatrics, University of California San Diego, La Jolla, CA, USA.
Nuno BandeiraSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
David J GonzalezSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
Doug ConradCenter for Microbiome Innovation, University of California San Diego, La Jolla, CA, USA.
Anthony J O'DonoghueSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
Rob KnightCenter for Microbiome Innovation, University of California San Diego, La Jolla, CA, USA.
Pieter C DorresteinSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA. pdorrestein@ucsd.edu.
University of California, San Diego · USMichigan State University · US

Funding

Systems Biology Approach to Redefine Susceptibility Testing and Treatment of MDR Pathogens in the Context of Host ImmunityU01AI124316 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PALSSON, BERNHARD O · 2016 to 2020
$10.2M
NIAID NIH HHS U01 AI124316
6 · The paper itself

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.

Indexed as

Amino AcidsCathepsin GCystic FibrosisDysbiosisHumansLeukocyte ElastaseLungMicrobiotaNeutrophilsProteolysisProteomePseudomonas aeruginosaRNA, Ribosomal, 16SSputumTandem Mass SpectrometryAmino AcidsCathepsin GCTSG protein, humanLeukocyte ElastaseProteomeRNA, Ribosomal, 16S

Identifiers

PMID30760325
PMCPMC6375204
OpenAlexW2935406968

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.