Evidence map›Paper›PMID 25182651›Full record

ArticleAntimicrobial agents and chemotherapy2014

Enhanced in vitro formation and antibiotic resistance of nonattached Pseudomonas aeruginosa aggregates through incorporation of neutrophil products.

Silvia M Caceres, Kenneth C Malcolm, Jennifer L Taylor-Cousar, David P Nichols, Milene T Saavedra, Donna L Bratton, Samuel M Moskowitz, Jane L Burns, Jerry A Nick

Open access · bronzeAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

29 citing papers in PubMed, 51 citations in OpenAlex.

  1. Impact of azithromycin on the clinical and antimicrobial effectiveness of tobramycin in the treatment of cystic fibrosis.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2017
    Trial
  2. Remodeling of the neutrophil proteome upon exposure toMicrobiology resource announcements · 2025
    Article
  3. Article
  4. Article
  5. Identification ofmBio · 2024
    Article
  6. What Is a Biofilm? Lessons Learned from Interactions with Immune Cells.International journal of molecular sciences · 2024
    Review
  7. Article
  8. Article
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  13. Response ofPeerJ · 2021
    Article
  14. Article
  15. Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. Bacterial autoaggregation.AIMS microbiology · 2018
    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

9 authors at 4 institutions in 1 country.

Silvia M CaceresDepartment of Medicine, National Jewish Health, Denver, Colorado, USA.
Kenneth C MalcolmDepartment of Medicine, National Jewish Health, Denver, Colorado, USA Department of Medicine, University of Colorado, Denver, Aurora, Colorado, USA malcolmk@njhealth.org.
Jennifer L Taylor-CousarDepartment of Medicine, National Jewish Health, Denver, Colorado, USA Department of Medicine, University of Colorado, Denver, Aurora, Colorado, USA.
David P NicholsDepartment of Medicine, National Jewish Health, Denver, Colorado, USA Department of Pediatrics, National Jewish Health, Denver, Colorado, USA Department of Medicine, University of Colorado, Denver, Aurora, Colorado, USA.
Milene T SaavedraDepartment of Medicine, National Jewish Health, Denver, Colorado, USA Department of Medicine, University of Colorado, Denver, Aurora, Colorado, USA.
Donna L BrattonDepartment of Pediatrics, National Jewish Health, Denver, Colorado, USA.
Samuel M MoskowitzDepartment of Pediatrics, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Jane L BurnsDivision of Pediatric Infectious Disease, Department of Pediatrics, Seattle Children's Hospital, University of Washington School of Medicine, Seattle, Washington, USA.
Jerry A NickDepartment of Medicine, National Jewish Health, Denver, Colorado, USA Department of Medicine, University of Colorado, Denver, Aurora, Colorado, USA.
University of Colorado Denver · USNational Jewish Health · USHarvard University · USSeattle Children's Hospital · US

Funding

TRANSLOCATION AND TRANSCELLULAR BIOSYNTHESISP01HL034303 · NHLBI · NATIONAL JEWISH HEALTH · PI BARKLEY, ROBERT · 1985 to 2015
$25.0M
Translational Research Center to Expedite Novel Therapies in Cystic FibrosisP30DK089507 · NIDDK · SEATTLE CHILDREN'S HOSPITAL · PI Christopher Hooper Goss, Lucas R Hoffman · 2010 to 2026
$21.4M
Reversal of Inflammatory Processes in CGDR01AI110408 · NIAID · NATIONAL JEWISH HEALTH · PI BRATTON, DONNA L · 2014 to 2018
$2.0M
NHLBI NIH HHS HL34303NHLBI NIH HHS P01 HL034303NIAID NIH HHS R01 AI110408NIDDK NIH HHS P30 DK089507
6 · The paper itself

Abstract

Pseudomonas aeruginosa is a major pathogen in cystic fibrosis (CF) lung disease. Children with CF are routinely exposed to P. aeruginosa from the natural environment, and by adulthood, 80% of patients are chronically infected. P. aeruginosa in the CF airway exhibits a unique biofilm-like structure, where it grows in small clusters or aggregates of bacteria in association with abundant polymers of neutrophil-derived components F-actin and DNA, among other components. These aggregates differ substantially in size and appearance compared to surface-attached in vitro biofilm models classically utilized for studies but are believed to share properties of surface-attached biofilms, including antibiotic resistance. However, little is known about the formation and function of surface-independent modes of biofilm growth, how they might be eradicated, and quorum sensing communication. To address these issues, we developed a novel in vitro model of P. aeruginosa aggregates incorporating human neutrophil-derived products. Aggregates grown in vitro and those found in CF patients' sputum samples were morphologically similar; viable bacteria were distributed in small pockets throughout the aggregate. The lasA quorum sensing gene was differentially expressed in the presence of neutrophil products. Importantly, aggregates formed in the presence of neutrophils acquired resistance to tobramycin, which was lost when the aggregates were dispersed with DNase, and antagonism of tobramycin and azithromycin was observed. This novel yet simple in vitro system advances our ability to model infection of the CF airway and will be an important tool to study virulence and test alternative eradication strategies against P. aeruginosa.

Indexed as

Anti-Bacterial AgentsAzithromycinBiofilmsCystic FibrosisDrug Resistance, Multiple, BacterialHumansMetalloproteasesMicrobial Sensitivity TestsNeutrophilsPseudomonas aeruginosaPseudomonas InfectionsQuorum SensingSputumTobramycinVirulence FactorsAnti-Bacterial AgentsAzithromycinLasA protein, Pseudomonas aeruginosaMetalloproteasesTobramycinVirulence Factors

Identifiers

PMID25182651
PMCPMC4249413
OpenAlexW2130663948

What OpenQuestion holds

Textmetadata
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.