Evidence map›Paper›PMID 30682135›Full record

ArticlePloS one2019

Tobramycin reduces key virulence determinants in the proteome of Pseudomonas aeruginosa outer membrane vesicles.

Katja Koeppen, Roxanna Barnaby, Angelyca A Jackson, Scott A Gerber, Deborah A Hogan, Bruce A Stanton

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

22 citing papers in PubMed, 32 citations in OpenAlex.

  1. Outer membrane vesicles secreted byInfection and immunity · 2026
    Article
  2. Review
  3. CombattingAntibiotics (Basel, Switzerland) · 2025
    Review
  4. Review
  5. Article
  6. American journal of physiology. Lung cellular and molecular physiology · 2024
    Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Sub-Inhibitory Antibiotic Exposure and Virulence inAntibiotics (Basel, Switzerland) · 2021
    Review
  15. Review
  16. Article
  17. Review
  18. Review
  19. Article
  20. The Role of Proteomics in Bacterial Response to Antibiotics.Pharmaceuticals (Basel, Switzerland) · 2020
    Review
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

6 authors at 1 institution in 1 country.

Katja KoeppenDepartment of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America.ORCID 0000-0003-1094-0621
Roxanna BarnabyDepartment of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America.
Angelyca A JacksonDepartment of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America.
Scott A GerberDepartment of Molecular and Systems Biology, The Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America.
Deborah A HoganDepartment of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America.
Bruce A StantonDepartment of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America.
Dartmouth College · US

Funding

TRANSLATIONAL RESEARCH COREP30GM106394 · NIGMS · DARTMOUTH COLLEGE · PI STANTON, BRUCE A. · 2013 to 2017
$6.1M
Role of Virulence Factors in Pseudomonas-Host InteractionsR01HL074175 · NHLBI · DARTMOUTH COLLEGE · PI STANTON, BRUCE A. · 2003 to 2018
$5.0M
Host-associated regulation of P. aeruginosa colonization and virulenceR01AI091702 · NIAID · DARTMOUTH COLLEGE · PI HOGAN, DEBORAH A · 2011 to 2015
$2.0M
Defining human kinase-substrate networks and their dynamic regulationR01GM122846 · NIGMS · DARTMOUTH COLLEGE · PI GERBER, SCOTT A. · 2017 to 2020
$1.5M
LC-Orbitrap MS/MS System for shotgun Proteomics at DartmouthS10OD016212 · OD · DARTMOUTH COLLEGE · PI GERBER, SCOTT A. · 2013 to 2013
$600k
NHLBI NIH HHS R01 HL074175NIAID NIH HHS R01 AI091702NIGMS NIH HHS P30 GM106394NIGMS NIH HHS R01 GM122846NIH HHS S10 OD016212
6 · The paper itself

Abstract

Tobramycin is commonly used to treat Pseudomonas aeruginosa lung infections in patients with Cystic Fibrosis (CF). Tobramycin treatment leads to increased lung function and fewer clinical exacerbations in CF patients, and modestly reduces the density of P. aeruginosa in the lungs. P. aeruginosa resides primarily in the mucus overlying lung epithelial cells and secretes outer membrane vesicles (OMVs) that diffuse through the mucus and fuse with airway epithelial cells, thus delivering virulence factors into the cytoplasm that modify the innate immune response. The goal of this study was to test the hypothesis that Tobramycin reduces the abundance of virulence factors in OMVs secreted by P. aeruginosa. Characterization of the proteome of OMVs isolated from control or Tobramycin-exposed P. aeruginosa strain PAO1 revealed that Tobramycin reduced several OMV-associated virulence determinants, including AprA, an alkaline protease that enhances P. aeruginosa survival in the lung, and is predicted to contribute to the inhibitory effect of P. aeruginosa on Phe508del-CFTR Cl- secretion by primary human bronchial epithelial cells. Deletion of the gene encoding AprA reduced the inhibitory effect of P. aeruginosa on Phe508del-CFTR Cl- secretion. Moreover, as predicted by our proteomic analysis, OMVs isolated from Tobramycin treated P. aeruginosa had a diminished inhibitory effect on Phe508del-CFTR Cl- secretion compared to OMVs isolated from control P. aeruginosa. Taken together, our proteomic analysis of OMVs and biological validation suggest that Tobramycin may improve lung function in CF patients infected with P. aeruginosa by reducing several key virulence factors in OMVs that reduce CFTR Cl- secretion, which is essential for bacterial clearance from the lungs.

Indexed as

Bacterial ProteinsBronchiCells, CulturedCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorExopeptidasesHumansImmunity, InnateProteomicsPseudomonas aeruginosaSecretory VesiclesTobramycinVirulenceBacterial ProteinsCFTR protein, humanCystic Fibrosis Transmembrane Conductance RegulatorExopeptidasesTobramycin

Identifiers

PMID30682135
PMCPMC6347270
OpenAlexW2914129368

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.