Evidence map›Paper›PMID 29742342›Full record

ArticleACS infectious diseases2018

Receptor-Based Peptides for Inhibition of Leukotoxin Activity.

Eric Krueger, Shannon Hayes, En Hyung Chang, Shailagne Yutuc, Angela C Brown

Abstract read
In one paragraph

Article in ACS infectious diseases, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.2field-weighted citation impact, top 23% 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

15 citing papers in PubMed, 20 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Microorganisms · 2022
    Review
  5. Article
  6. Article
  7. Review
  8. Review
  9. Article
  10. Article
  11. Review
  12. Review
  13. Catechin-mediated restructuring of a bacterial toxin inhibits activity.Biochimica et biophysica acta. General subjects · 2019
    Article
  14. Toxins · 2018
    Article
  15. 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

5 authors at 1 institution in 1 country.

Eric KruegerDepartment of Chemical and Biomolecular Engineering , Lehigh University , Iacocca Hall, Room B323, 111 Research Drive , Bethlehem , Pennsylvania 18015 , United States.
Shannon HayesDepartment of Chemical and Biomolecular Engineering , Lehigh University , Iacocca Hall, Room B323, 111 Research Drive , Bethlehem , Pennsylvania 18015 , United States.
En Hyung ChangDepartment of Chemical and Biomolecular Engineering , Lehigh University , Iacocca Hall, Room B323, 111 Research Drive , Bethlehem , Pennsylvania 18015 , United States.
Shailagne YutucDepartment of Chemical and Biomolecular Engineering , Lehigh University , Iacocca Hall, Room B323, 111 Research Drive , Bethlehem , Pennsylvania 18015 , United States.
Angela C BrownDepartment of Chemical and Biomolecular Engineering , Lehigh University , Iacocca Hall, Room B323, 111 Research Drive , Bethlehem , Pennsylvania 18015 , United States.ORCID 0000-0003-1038-8216
Lehigh University · US

Funding

Cytotoxic mechanisms of Aggregatibacter actinomycetemcomitans leukotoxinR00DE022795 · NIDCR · LEHIGH UNIVERSITY · PI BROWN, ANGELA C. · 2014 to 2016
$838k
Mechanism of A. actinomycetemcomitans Outer Membrane Vesicle Delivery to Target CellsR03DE025275 · NIDCR · LEHIGH UNIVERSITY · PI BROWN, ANGELA C. · 2016 to 2017
$226k
Cytotoxic mechanisms of Aggregatibacter actinomycetemcomitans leukotoxinK99DE022795 · NIDCR · UNIVERSITY OF PENNSYLVANIA · PI BROWN, ANGELA C. · 2012 to 2013
$155k
Combined Contribution of the Integrin LFA-1 Cholesterol to Leukotoxin ActivityF32DE026962 · NIDCR · LEHIGH UNIVERSITY · PI KRUEGER, ERIC · 2017 to 2018
$132k
NIDCR NIH HHS F32 DE026962NIDCR NIH HHS K99 DE022795NIDCR NIH HHS R00 DE022795NIDCR NIH HHS R03 DE025275
6 · The paper itself

Abstract

The Gram-negative bacterium Aggregatibacter actinomycetemcomitans, commonly associated with localized aggressive periodontitis (LAP), secretes an RTX (repeats-in-toxin) protein leukotoxin (LtxA) that targets human white blood cells, an interaction that is driven by its recognition of the lymphocyte function-associated antigen-1 (LFA-1) integrin. In this study, we report on the inhibition of LtxA-LFA-1 binding as an antivirulence strategy to inhibit LtxA-mediated cytotoxicity. Specifically, we designed and synthesized peptides corresponding to the reported LtxA binding domain on LFA-1 and characterized their capability to inhibit LtxA binding to LFA-1 and subsequent cytotoxic activity in human immune cells. We found that several of these peptides, corresponding to sequential β-strands in the LtxA-binding domain of LFA-1, inhibit LtxA activity, demonstrating the effectiveness of this approach. Further investigations into the mechanism by which these peptides inhibit LtxA binding to LFA-1 reveal a correlation between toxin-peptide affinity and LtxA-mediated cytotoxicity, leading to a diminished association between LtxA and LFA-1 on the cell membrane. Our results demonstrate the possibility of using target-based peptides to inhibit LtxA activity, and we expect that a similar approach could be used to hinder the activity of other RTX toxins.

Indexed as

Amino Acid SequenceAnti-Bacterial AgentsExotoxinsHumansLymphocyte Function-Associated Antigen-1Models, BiologicalPeptidesProtein BindingStructure-Activity RelationshipTHP-1 CellsVirulence FactorsAnti-Bacterial AgentsExotoxinsleukotoxinLymphocyte Function-Associated Antigen-1PeptidesVirulence FactorsAggregatibacter actinomycetemcomitansantivirulenceleukotoxinlymphocyte function-associated antigen-1peptide therapeuticsrepeats-in-toxinRTX

Identifiers

PMID29742342
PMCPMC6050581
OpenAlexW2800151967

What OpenQuestion holds

Textmetadata
LicenceTDM
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.