Evidence map›Paper›PMID 24798289›Full record

ArticleAntimicrobial agents and chemotherapy2014

Screening for inhibition of Vibrio cholerae VipA-VipB interaction identifies small-molecule compounds active against type VI secretion.

Kun Sun, Jeanette Bröms, Moa Lavander, Bharat Kumar Gurram, Per-Anders Enquist, C David Andersson, Mikael Elofsson, Anders Sjöstedt

Open access · bronzeAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
0.7field-weighted citation impact, top 29% 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

12 citing papers in PubMed, 16 citations in OpenAlex.

  1. Article
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  3. Proteomic Analysis of the Fish PathogenAnimals : an open access journal from MDPI · 2024
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  4. Article
  5. Review
  6. Article
  7. Sensing of intracellular Hcp levels controls T6SS expression inProceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Generation of reactive oxygen species by lethal attacks from competing microbes.Proceedings of the National Academy of Sciences of the United States of America · 2015
    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

8 authors at 1 institution in 1 country.

Kun SunDepartment of Clinical Microbiology, Clinical Bacteriology and Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, Sweden.
Jeanette BrömsDepartment of Clinical Microbiology, Clinical Bacteriology and Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, Sweden.
Moa LavanderDepartment of Clinical Microbiology, Clinical Bacteriology and Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, Sweden.
Bharat Kumar GurramDepartment of Clinical Microbiology, Clinical Bacteriology and Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, Sweden.
Per-Anders EnquistDepartment of Chemistry and Laboratories for Chemical Biology Umeå (LCBU), Umeå University, Umeå, Sweden.
C David AnderssonDepartment of Chemistry and Laboratories for Chemical Biology Umeå (LCBU), Umeå University, Umeå, Sweden.
Mikael ElofssonDepartment of Chemistry and Laboratories for Chemical Biology Umeå (LCBU), Umeå University, Umeå, Sweden.
Anders SjöstedtDepartment of Clinical Microbiology, Clinical Bacteriology and Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, Sweden Anders.Sjöstedt@climi.umu.se.
Umeå University · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The type VI secretion system (T6SS) is the most prevalent bacterial secretion system and an important virulence mechanism utilized by Gram-negative bacteria, either to target eukaryotic cells or to combat other microbes. The components show much variability, but some appear essential for the function, and two homologues, denoted VipA and VipB in Vibrio cholerae, have been identified in all T6SSs described so far. Secretion is dependent on binding of an α-helical region of VipA to VipB, and in the absence of this binding, both components are degraded within minutes and secretion is ceased. The aim of the study was to investigate if this interaction could be blocked, and we hypothesized that such inhibition would lead to abrogation of T6S. A library of 9,600 small-molecule compounds was screened for their ability to block the binding of VipA-VipB in a bacterial two-hybrid system (B2H). After excluding compounds that showed cytotoxicity toward eukaryotic cells, that inhibited growth of Vibrio, or that inhibited an unrelated B2H interaction, 34 compounds were further investigated for effects on the T6SS-dependent secretion of hemolysin-coregulated protein (Hcp) or of phospholipase A1 activity. Two compounds, KS100 and KS200, showed intermediate or strong effects in both assays. Analogues were obtained, and compounds with potent inhibitory effects in the assays and desirable physicochemical properties as predicted by in silico analysis were identified. Since the compounds specifically target a virulence mechanism without affecting bacterial replication, they have the potential to mitigate the virulence with minimal risk for development of resistance.

Indexed as

Anti-Bacterial AgentsBacterial ProteinsBacterial Secretion SystemsHemolysin ProteinsMicrobial Sensitivity TestsMolecular Sequence DataPhospholipases A1Vibrio choleraeVirulence FactorsAnti-Bacterial AgentsBacterial ProteinsBacterial Secretion SystemsHcp protein, Vibrio choleraeHemolysin ProteinsPhospholipases A1Virulence Factors

Identifiers

PMID24798289
PMCPMC4068513
OpenAlexW2165024505

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.