Evidence map›Paper›PMID 34396989›Full record

ArticleThe Journal of clinical investigation2021

The extracellular innate-immune effector HMGB1 limits pathogenic bacterial biofilm proliferation.

Aishwarya Devaraj, Laura A Novotny, Frank H Robledo-Avila, John R Buzzo, Lauren Mashburn-Warren, Joseph A Jurcisek, Natalia O Tjokro, Santiago Partida-Sanchez, Lauren O Bakaletz, Steven D Goodman

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.6field-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

13 citing papers in PubMed, 24 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Extracellular DNA-protein interactions.Current opinion in structural biology · 2024
    Review
  5. Review
  6. Anti-Biofilm Effects of Z102-E ofFoods (Basel, Switzerland) · 2024
    Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. Review
  13. Article
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

10 authors at 2 institutions in 1 country.

Aishwarya DevarajCenter for Microbial Pathogenesis, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
Laura A NovotnyCenter for Microbial Pathogenesis, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
Frank H Robledo-AvilaCenter for Microbial Pathogenesis, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
John R BuzzoCenter for Microbial Pathogenesis, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
Lauren Mashburn-WarrenThe Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, Ohio, USA.
Joseph A JurcisekCenter for Microbial Pathogenesis, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
Natalia O TjokroDivision of Periodontology, Diagnostic Sciences, and Dental Hygiene, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, California, USA.
Santiago Partida-SanchezCenter for Microbial Pathogenesis, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
Lauren O BakaletzCenter for Microbial Pathogenesis, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
Steven D GoodmanCenter for Microbial Pathogenesis, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
Nationwide Children's Hospital · USUniversity of Southern California · US

Funding

Novel immunotherapeutics for the management of otitis media due to H. influenzaeR01DC011818 · NIDCD · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI BAKALETZ, LAUREN O, GOODMAN, STEVEN D · 2011 to 2020
$5.4M
HMGB1-mediated host response to chronic bacterial infectionR01AI155501 · NIAID · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI GOODMAN, STEVEN D · 2020 to 2024
$3.6M
NIAID NIH HHS R01 AI155501NIDCD NIH HHS R01 DC011818
6 · The paper itself

Abstract

Herein, we describe an extracellular function of the vertebrate high-mobility group box 1 protein (HMGB1) in the proliferation of bacterial biofilms. Within host cells, HMGB1 functions as a DNA architectural protein, similar to the ubiquitous DNABII family of bacterial proteins; despite that, these proteins share no amino acid sequence identity. Extracellularly, HMGB1 induces a proinflammatory immune response, whereas the DNABII proteins stabilize the extracellular DNA-dependent matrix that maintains bacterial biofilms. We showed that when both proteins converged on extracellular DNA within bacterial biofilms, HMGB1, unlike the DNABII proteins, disrupted biofilms both in vitro (including the high-priority ESKAPEE pathogens) and in vivo in 2 distinct animal models, albeit with induction of a strong inflammatory response that we attenuated by a single engineered amino acid change. We propose a model where extracellular HMGB1 balances the degree of induced inflammation and biofilm containment without excessive release of biofilm-resident bacteria.

Indexed as

AnimalsBacterial ProteinsBiofilmsChinchillaDNA, BacterialExtracellular MatrixExtracellular TrapsFemaleHMGB1 ProteinHost Microbial InteractionsHumansImmunity, InnateMaleMiceMice, Inbred C57BLModels, ImmunologicalBacterial ProteinsDNA, BacterialHMGB1 ProteinBacterial infectionsDrug therapyImmunologyImmunotherapyInfectious disease

Identifiers

PMID34396989
PMCPMC8363290
OpenAlexW3195778116

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.