Evidence map›Paper›PMID 21909403›Full record

ArticlePloS one2011

Neutrophil extracellular trap (NET)-mediated killing of Pseudomonas aeruginosa: evidence of acquired resistance within the CF airway, independent of CFTR.

Robert L Young, Kenneth C Malcolm, Jennifer E Kret, Silvia M Caceres, Katie R Poch, David P Nichols, Jennifer L Taylor-Cousar, Milene T Saavedra, Scott H Randell, Michael L Vasil and 3 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 133 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
133citing papers in PubMed, 3 pooled it
14.5field-weighted citation impact, top 1% 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

133 citing papers in PubMed, 3 syntheses or guidelines pooled it, 220 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Review
  6. Review
  7. Review
  8. Dipeptidyl peptidase-1 inhibitors in bronchiectasis.European respiratory review : an official journal of the European Respiratory Society · 2025
    Review
  9. Article
  10. Article
  11. Divergent host humoral innate immune response to the smooth-to-rough adaptation ofFrontiers in cellular and infection microbiology · 2025
    Article
  12. Review
  13. Review
  14. Review
  15. Infection and the microbiome in bronchiectasis.European respiratory review : an official journal of the European Respiratory Society · 2024
    Review
  16. Review
  17. Review
  18. CFTR is required for zinc-mediated antibacterial defense in human macrophages.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  19. Article
  20. Neutrophils in Physiology and Pathology.Annual review of pathology · 2024
    Review

73 more citing papers are in PubMed but not listed here.

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

13 authors at 6 institutions in 1 country.

Robert L YoungDepartment of Medicine, National Jewish Health, Denver, Colorado, United States of America. rlyoung630@gmail.com
Kenneth C Malcolm
Jennifer E Kret
Silvia M Caceres
Katie R Poch
David P Nichols
Jennifer L Taylor-Cousar
Milene T Saavedra
Scott H Randell
Michael L Vasil
Jane L Burns
Samuel M Moskowitz
Jerry A Nick
National Jewish Health · USUniversity of Colorado Denver · USMassachusetts General Hospital · USSeattle Children's Hospital · USUniversity of Colorado Anschutz Medical Campus · USUniversity of North Carolina at Chapel Hill · US

Funding

INSTITUTE FOR TRANSLATIONAL HEALTH SCIENCE (UL1): BPCAUL1RR025014 · NCRR · UNIVERSITY OF WASHINGTON · PI DISIS, MARY L. · 2007 to 2011
$51.5M
Vector CoreP30DK065988 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Richard Charles Boucher, Martina Gentzsch · 2004 to 2026
$26.5M
Iron and O2 in the Regulation of P. aeruginosa VirulenceR37AI015940 · NIAID · UNIVERSITY OF COLORADO DENVER · PI VASIL, MICHAEL L. · 2003 to 2012
$5.1M
Viral-induced Adaptation of Neutrophil Response in ARDSR01HL090991 · NHLBI · NATIONAL JEWISH HEALTH · PI NICK, JERRY A · 2007 to 2010
$1.7M
NCRR NIH HHS UL1 RR025014NHLBI NIH HHS 1R01HL090991NHLBI NIH HHS R01 HL090991NIAID NIH HHS R37 AI015940NIAID NIH HHS R37AI15940NIDDK NIH HHS P30 DK065988NIDDK NIH HHS P30DK065988
6 · The paper itself

Abstract

The inability of neutrophils to eradicate Pseudomonas aeruginosa within the cystic fibrosis (CF) airway eventually results in chronic infection by the bacteria in nearly 80 percent of patients. Phagocytic killing of P. aeruginosa by CF neutrophils is impaired due to decreased cystic fibrosis transmembrane conductance regulator (CFTR) function and virulence factors acquired by the bacteria. Recently, neutrophil extracellular traps (NETs), extracellular structures composed of neutrophil chromatin complexed with granule contents, were identified as an alternative mechanism of pathogen killing. The hypothesis that NET-mediated killing of P. aeruginosa is impaired in the context of the CF airway was tested. P. aeruginosa induced NET formation by neutrophils from healthy donors in a bacterial density dependent fashion. When maintained in suspension through continuous rotation, P. aeruginosa became physically associated with NETs. Under these conditions, NETs were the predominant mechanism of killing, across a wide range of bacterial densities. Peripheral blood neutrophils isolated from CF patients demonstrated no impairment in NET formation or function against P. aeruginosa. However, isogenic clinical isolates of P. aeruginosa obtained from CF patients early and later in the course of infection demonstrated an acquired capacity to withstand NET-mediated killing in 8 of 9 isolates tested. This resistance correlated with development of the mucoid phenotype, but was not a direct result of the excess alginate production that is characteristic of mucoidy. Together, these results demonstrate that neutrophils can kill P. aeruginosa via NETs, and in vitro this response is most effective under non-stationary conditions with a low ratio of bacteria to neutrophils. NET-mediated killing is independent of CFTR function or bacterial opsonization. Failure of this response in the context of the CF airway may occur, in part, due to an acquired resistance against NET-mediated killing by CF strains of P. aeruginosa.

Indexed as

Microbial ViabilityAnti-Bacterial AgentsCell AdhesionCell SeparationCellular StructuresCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorExtracellular SpaceHumansLungMicrobial Sensitivity TestsNeutrophilsPseudomonas aeruginosaSuspensionsAnti-Bacterial AgentsCystic Fibrosis Transmembrane Conductance RegulatorSuspensions

Identifiers

PMID21909403
PMCPMC3164657
OpenAlexW2001336488

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.