Evidence map›Paper›PMID 25229185›Full record

ArticleFree radical biology & medicine2014

Nitrite modulates bacterial antibiotic susceptibility and biofilm formation in association with airway epithelial cells.

Anna C Zemke, Sruti Shiva, Jane L Burns, Samuel M Moskowitz, Joseph M Pilewski, Mark T Gladwin, Jennifer M Bomberger

Registry-linked trialOpen access · greenAbstract read
In one paragraph

Article in Free radical biology & medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02694393 (Phase I/II Study of Inhaled Sodium Nitrite as an Antimicrobial for Pseudomonas Infection in Cystic Fibrosis), which is not on this map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
4.6field-weighted citation impact, top 5% 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.

NCT02694393 phase1 / phase2terminatednot on this mapstarted 2016, after this paper: background citation

Phase I/II Study of Inhaled Sodium Nitrite as an Antimicrobial for Pseudomonas Infection in Cystic Fibrosis

TypeinterventionalSponsorSchmidhofer, Mark, MDRan2016 to 2022Enrolled4ConditionsCystic FibrosisArmssodium nitrite
3 · Its place in the literature

Who cites it

44 citing papers in PubMed, 61 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Microbiology spectrum · 2025
    Article
  5. Nicorandil reduces the antimicrobial effectiveness of polymyxin E againstFrontiers in cellular and infection microbiology · 2025
    Article
  6. Recreating chronic respiratory infectionsEuropean respiratory review : an official journal of the European Respiratory Society · 2024
    Review
  7. Article
  8. Review
  9. Biofilm · 2023
    Article
  10. Article
  11. Bacterial respiratory inhibition triggers dispersal ofApplied and environmental microbiology · 2023
    Article
  12. Anti-Microorganisms · 2023
    Review
  13. Article
  14. Article
  15. Review
  16. Complex Interplay of Heme-Copper Oxidases with Nitrite and Nitric Oxide.International journal of molecular sciences · 2022
    Review
  17. The cystic fibrosis lung microenvironment alters antibiotic activity: causes and effects.European respiratory review : an official journal of the European Respiratory Society · 2021
    Review
  18. Review
  19. Article
  20. 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

7 authors at 3 institutions in 1 country.

Anna C ZemkeDivision of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA.
Sruti ShivaDepartment of Pharmacology, University of Pittsburgh, Pittsburgh, PA 15219, USA.
Jane L BurnsDepartment of Pediatrics, University of Washington, Seattle, WA 98195, USA.
Samuel M MoskowitzDepartment of Pediatrics, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Joseph M PilewskiDivision of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA.
Mark T GladwinDivision of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA; Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, Pittsburgh, PA 15219, USA.
Jennifer M BombergerDepartment of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15219, USA. Electronic address: jbomb@pitt.edu.
University of Pittsburgh · USMassachusetts General Hospital · USUniversity of Washington · US

Funding

Vascular Subphenotypes of Lung DiseaseP01HL103455 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GLADWIN, MARK T · 2011 to 2020
$26.1M
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
Translational StudiesP30DK072506 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI PILEWSKI, JOSEPH MARK · 2005 to 2017
$12.5M
Storage Lesion in Banked Blood Due to Disruption of Nitric Oxide HomeostasisR01HL098032 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Mark T Gladwin · 2009 to 2026
$12.5M
Translational Training Program in Pulmonary Biology and MedicineT32HL007563 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Melanie Koenigshoff · 1985 to 2026
$12.3M
Translational Pulmonary Vascular BiologyT32HL110849 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Sruti Shiva · 2012 to 2026
$5.0M
SCOR: CFTR IN AIRWAY CELL FUNCTIONP50DK056490 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FRIZZELL, RAYMOND A · 1999 to 2004
$5.0M
Polymyxin-resistant Pseudomonas in CF Lung InfectionR01AI067653 · NIAID · UNIVERSITY OF WASHINGTON · PI MOSKOWITZ, SAMUEL M · 2007 to 2010
$2.5M
Viral-bacterial co-infections in the lungR01HL123771 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BOMBERGER, JENNIFER MELINDA · 2015 to 2018
$1.5M
Myoglobin as a Nitrite Reductase that Regulates Hypoxic Cardiac NO SignalingR01HL096973 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GLADWIN, MARK T, SHIVA, SRUTI · 2010 to 2013
$1.5M
Polymicrobial Interactions in the LungR00HL098342 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BOMBERGER, JENNIFER MELINDA · 2011 to 2013
$735k
NHLBI NIH HHS 2T32HL007563-26NHLBI NIH HHS L40 HL104736NHLBI NIH HHS P01 HL103455NHLBI NIH HHS P01HL103455NHLBI NIH HHS R00 HL098342NHLBI NIH HHS R00HL098342-01NHLBI NIH HHS R01 HL096973NHLBI NIH HHS R01HL096973NHLBI NIH HHS R01 HL098032NHLBI NIH HHS R01HL098032NHLBI NIH HHS R01 HL123771NHLBI NIH HHS T32 HL007563NHLBI NIH HHS T32 HL110849NHLBI NIH HHS T32HL110849NIAID NIH HHS R01 AI067653NIAID NIH HHS R01AI067653NIDDK NIH HHS 5P30DK089507-04NIDDK NIH HHS P30 DK072506NIDDK NIH HHS P30DK072506NIDDK NIH HHS P30 DK089507NIDDK NIH HHS P50 DK056490
6 · The paper itself

Abstract

Pseudomonas aeruginosa is the major pathogenic bacteria in cystic fibrosis and other forms of bronchiectasis. Growth in antibiotic-resistant biofilms contributes to the virulence of this organism. Sodium nitrite has antimicrobial properties and has been tolerated as a nebulized compound at high concentrations in human subjects with pulmonary hypertension; however, its effects have not been evaluated on biotic biofilms or in combination with other clinically useful antibiotics. We grew P. aeruginosa on the apical surface of primary human airway epithelial cells to test the efficacy of sodium nitrite against biotic biofilms. Nitrite alone prevented 99% of biofilm growth. We then identified significant cooperative interactions between nitrite and polymyxins. For P. aeruginosa growing on primary CF airway cells, combining nitrite and colistimethate resulted in an additional log of bacterial inhibition compared to treating with either agent alone. Nitrite and colistimethate additively inhibited oxygen consumption by P. aeruginosa. Surprisingly, whereas the antimicrobial effects of nitrite in planktonic, aerated cultures are nitric oxide (NO) dependent, antimicrobial effects under other growth conditions are not. The inhibitory effect of nitrite on bacterial oxygen consumption and biofilm growth did not require NO as an intermediate as chemically scavenging NO did not block growth inhibition. These data suggest an NO-radical independent nitrosative or oxidative inhibition of respiration. The combination of nebulized sodium nitrite and colistimethate may provide a novel therapy for chronic P. aeruginosa airway infections, because sodium nitrite, unlike other antibiotic respiratory chain "poisons," can be safely nebulized at high concentration in humans.

Indexed as

BiofilmsDrug Resistance, BacterialAnti-Bacterial AgentsBronchiCells, CulturedColistinEpithelial CellsHumansMicrobial Sensitivity TestsNitric OxideOxygenPseudomonas aeruginosaSodium NitriteAnti-Bacterial AgentsColistinNitric OxideOxygenSodium NitriteBiofilmColistimethateColistinPolymyxinPseudomonas aeruginosaSodium nitrite

Identifiers

PMID25229185
PMCPMC4278422
OpenAlexW2044668858

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Registered trials

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.