Evidence map›Paper›PMID 22850508›Full record

ArticleAntimicrobial agents and chemotherapy2012

Identification of small molecules that antagonize diguanylate cyclase enzymes to inhibit biofilm formation.

Karthik Sambanthamoorthy, Rudolph E Sloup, Vijay Parashar, Joshua M Smith, Eric E Kim, Martin F Semmelhack, Matthew B Neiditch, Christopher M Waters

Open access · bronzeAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed
5.4field-weighted citation impact, top 3% 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

63 citing papers in PubMed, 153 citations in OpenAlex.

  1. Review
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  10. L-Ascorbic Acid RestrictsMicroorganisms · 2024
    Article
  11. The Bacterial Biofilms: Formation, Impacts, and Possible Management Targets in the Healthcare System.The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale · 2024
    Review
  12. Nucleotides as Bacterial Second Messengers.Molecules (Basel, Switzerland) · 2023
    Review
  13. Article
  14. Review
  15. Article
  16. Review
  17. Article
  18. Article
  19. Transcriptional Profiling of Pseudomonas aeruginosa Infections.Advances in experimental medicine and biology · 2022
    Review
  20. Controlling Biofilm Development Through Cyclic di-GMP Signaling.Advances in experimental medicine and biology · 2022
    Review

3 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

8 authors at 3 institutions in 1 country.

Karthik SambanthamoorthyDepartment of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, USA.
Rudolph E Sloup
Vijay Parashar
Joshua M Smith
Eric E Kim
Martin F Semmelhack
Matthew B Neiditch
Christopher M Waters
Michigan State University · USPrinceton University · USRutgers, The State University of New Jersey · US

Funding

Vaccines and Therapies Against BotulismU54AI057153 · NIAID · UNIVERSITY OF CHICAGO · PI SHUMAN, HOWARD A · 2003 to 2013
$87.6M
The Impact of Microbiome Composition, Diversity, and Function on Enteric DiseaseU19AI090872 · NIAID · MICHIGAN STATE UNIVERSITY · PI MANSFIELD, LINDA S. · 2010 to 2014
$7.1M
Structural Biology of Multifunctional Bacterial PhosphatasesR01AI081736 · NIAID · UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL · PI NEIDITCH, MATTHEW B · 2009 to 2012
$1.5M
Characterization of the Cyclic Di-GMP Signaling System of Vibrio choleraeK22AI080937 · NIAID · MICHIGAN STATE UNIVERSITY · PI WATERS, CHRISTOPHER M · 2009 to 2010
$275k
NIAID NIH HHS 2-U54-AI-057153NIAID NIH HHS K22 AI080937NIAID NIH HHS K22AI080937NIAID NIH HHS R01 AI081736NIAID NIH HHS R01AI081736NIAID NIH HHS U19 AI090872NIAID NIH HHS U54 AI057153
6 · The paper itself

Abstract

Bacterial biofilm formation is responsible for numerous chronic infections, causing a severe health burden. Many of these infections cannot be resolved, as bacteria in biofilms are resistant to the host's immune defenses and antibiotic therapy. New strategies to treat biofilm-based infections are critically needed. Cyclic di-GMP (c-di-GMP) is a widely conserved second-messenger signal essential for biofilm formation. As this signaling system is found only in bacteria, it is an attractive target for the development of new antibiofilm interventions. Here, we describe the results of a high-throughput screen to identify small-molecule inhibitors of diguanylate cyclase (DGC) enzymes that synthesize c-di-GMP. We report seven small molecules that antagonize these enzymes and inhibit biofilm formation by Vibrio cholerae. Moreover, two of these compounds significantly reduce the total concentration of c-di-GMP in V. cholerae, one of which also inhibits biofilm formation by Pseudomonas aeruginosa in a continuous-flow system. These molecules represent the first compounds described that are able to inhibit DGC activity to prevent biofilm formation.

Indexed as

Anti-Bacterial AgentsBacterial ProteinsBiofilmsCyclic GMPEscherichia coli ProteinsPhosphorus-Oxygen LyasesPseudomonas aeruginosaVibrio choleraeAnti-Bacterial AgentsBacterial Proteinsbis(3',5')-cyclic diguanylic acidCyclic GMPdiguanylate cyclaseEscherichia coli ProteinsPhosphorus-Oxygen Lyases

Identifiers

PMID22850508
PMCPMC3457405
OpenAlexW2028000414

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.