Evidence map›Paper›PMID 26856845›Full record

ArticleAntimicrobial agents and chemotherapy2016

Low Concentrations of Nitric Oxide Modulate Streptococcus pneumoniae Biofilm Metabolism and Antibiotic Tolerance.

Raymond N Allan, Samantha Morgan, Sanjita Brito-Mutunayagam, Paul Skipp, Martin Feelisch, Stephen M Hayes, William Hellier, Stuart C Clarke, Paul Stoodley, Andrea Burgess and 5 more

Open access · bronzeAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
4.5field-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.

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

18 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.

  1. Pooled it
  2. Induction of Nitric Oxide and Its Role in Otitis Media.Antioxidants (Basel, Switzerland) · 2025
    Review
  3. Article
  4. Article
  5. Review
  6. Biofilm aggregates and the host airway-microbial interface.Frontiers in cellular and infection microbiology · 2022
    Review
  7. Rapid, Simple, and Highly Specific Detection ofFrontiers in cellular and infection microbiology · 2022
    Article
  8. Article
  9. Review
  10. Meningitis Caused byAnimals : an open access journal from MDPI · 2020
    Article
  11. Panel 7 - Pathogenesis of otitis media - a review of the literature between 2015 and 2019.International journal of pediatric otorhinolaryngology · 2020
    Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. 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

15 authors at 4 institutions in 2 countries.

Raymond N AllanClinical and Experimental Sciences, Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, United Kingdom Southampton NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.
Samantha MorganClinical and Experimental Sciences, Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, United Kingdom.
Sanjita Brito-MutunayagamClinical and Experimental Sciences, Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, United Kingdom.
Paul SkippCentre for Biological Sciences, University of Southampton, Southampton, United Kingdom Centre for Proteomic Research, Institute for Life Sciences, University of Southampton, Southampton, United Kingdom.
Martin FeelischClinical and Experimental Sciences, Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, United Kingdom Southampton NIHR Respiratory Biomedical Research Unit, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.
Stephen M HayesClinical and Experimental Sciences, Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, United Kingdom.
William HellierUniversity Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.
Stuart C ClarkeClinical and Experimental Sciences, Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, United Kingdom Southampton NIHR Respiratory Biomedical Research Unit, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.
Paul StoodleyCentre for Biological Sciences, University of Southampton, Southampton, United Kingdom Department of Microbial Infection and Immunity, Centre for Microbial Interface Biology, College of Medicine, The Ohio State University, Columbus, Ohio, USA.
Andrea BurgessUniversity Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.
Hasnaa Ismail-KochUniversity Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.
Rami J SalibClinical and Experimental Sciences, Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, United Kingdom Southampton NIHR Respiratory Biomedical Research Unit, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.
Jeremy S WebbCentre for Biological Sciences, University of Southampton, Southampton, United Kingdom Southampton NIHR Respiratory Biomedical Research Unit, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.
Saul N FaustClinical and Experimental Sciences, Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, United Kingdom Southampton NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom Southampton NIHR Respiratory Biomedical Research Unit, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom s.faust@soton.ac.uk.
Luanne Hall-StoodleyClinical and Experimental Sciences, Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, United Kingdom Southampton NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom Department of Microbial Infection and Immunity, Centre for Microbial Interface Biology, College of Medicine, The Ohio State University, Columbus, Ohio, USA.
University of Southampton · GBUniversity Hospital Southampton NHS Foundation Trust · GBThe Ohio State University · USWellcome Trust · GB

Funding

Wellcome Trust
6 · The paper itself

Abstract

Streptococcus pneumoniaeis one of the key pathogens responsible for otitis media (OM), the most common infection in children and the largest cause of childhood antibiotic prescription. Novel therapeutic strategies that reduce the overall antibiotic consumption due to OM are required because, although widespread pneumococcal conjugate immunization has controlled invasive pneumococcal disease, overall OM incidence has not decreased. Biofilm formation represents an important phenotype contributing to the antibiotic tolerance and persistence ofS. pneumoniaein chronic or recurrent OM. We investigated the treatment of pneumococcal biofilms with nitric oxide (NO), an endogenous signaling molecule and therapeutic agent that has been demonstrated to trigger biofilm dispersal in other bacterial species. We hypothesized that addition of low concentrations of NO to pneumococcal biofilms would improve antibiotic efficacy and that higher concentrations exert direct antibacterial effects. Unlike in many other bacterial species, low concentrations of NO did not result inS. pneumoniaebiofilm dispersal. Instead, treatment of bothin vitrobiofilms andex vivoadenoid tissue samples (a reservoir forS. pneumoniaebiofilms) with low concentrations of NO enhanced pneumococcal killing when combined with amoxicillin-clavulanic acid, an antibiotic commonly used to treat chronic OM. Quantitative proteomic analysis using iTRAQ (isobaric tag for relative and absolute quantitation) identified 13 proteins that were differentially expressed following low-concentration NO treatment, 85% of which function in metabolism or translation. Treatment with low-concentration NO, therefore, appears to modulate pneumococcal metabolism and may represent a novel therapeutic approach to reduce antibiotic tolerance in pneumococcal biofilms.

Indexed as

AdenoidsAmoxicillin-Potassium Clavulanate CombinationAnti-Bacterial AgentsBiofilmsChildChild, PreschoolDrug Resistance, BacterialDrug SynergismDrug Therapy, CombinationGene Expression Regulation, BacterialHumansHydrazinesNitratesNitric OxideNitric Oxide DonorsNitroprusside1,1-diethyl-2-hydroxy-2-nitrosohydrazineAmoxicillin-Potassium Clavulanate CombinationAnti-Bacterial AgentsHydrazinesNitratesNitric OxideNitric Oxide DonorsNitroprussidesodium nitrateSodium Nitrite

Identifiers

PMID26856845
PMCPMC4808185
OpenAlexW2284524636

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.