Evidence map›Paper›PMID 26352738›Full record

ArticleMolecular oral microbiology2016

Inhibition of LtxA toxicity by blocking cholesterol binding with peptides.

A C Brown, E Koufos, N V Balashova, K Boesze-Battaglia, E T Lally

Abstract read
In one paragraph

Article in Molecular oral microbiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

21 citing papers in PubMed, 33 citations in OpenAlex.

  1. Article
  2. Microsomal triglyceride transfer protein is necessary to maintain lipid homeostasis and retinal function.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024
    Article
  3. Review
  4. Article
  5. Article
  6. Microorganisms · 2022
    Review
  7. Article
  8. Article
  9. Review
  10. Pathogens (Basel, Switzerland) · 2020
    Article
  11. Toxins · 2019
    Review
  12. Review
  13. Catechin-mediated restructuring of a bacterial toxin inhibits activity.Biochimica et biophysica acta. General subjects · 2019
    Article
  14. Article
  15. Toxins · 2018
    Article
  16. Article
  17. Cholesterol promotes Cytolysin A activity by stabilizing the intermediates during pore formation.Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  18. Article
  19. Article
  20. 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 2 institutions in 1 country.

A C BrownDepartment of Chemical and Biomolecular Engineering, Lehigh University, Bethlehem, PA, USA.
E KoufosDepartment of Chemical and Biomolecular Engineering, Lehigh University, Bethlehem, PA, USA.
N V BalashovaDepartment of Pathology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
K Boesze-BattagliaDepartment of Biochemistry, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
E T LallyDepartment of Pathology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
University of Pennsylvania · USLehigh University · US

Funding

Scientific TransparencyP30EY001583 · NEI · UNIVERSITY OF PENNSYLVANIA · PI CLAIRE H MITCHELL · 1985 to 2026
$19.5M
VIRULENCE FACTORS IN PERIODONTAL DISEASER01DE009517 · NIDCR · UNIVERSITY OF PENNSYLVANIA · PI BALASHOVA, NATALIYA V · 1990 to 2018
$5.2M
Lysosomal maturation during periodontal infectionsR01DE022465 · NIDCR · UNIVERSITY OF PENNSYLVANIA · PI BOESZE-BATTAGLIA, KATHLEEN · 2012 to 2016
$2.0M
Cytotoxic mechanisms of Aggregatibacter actinomycetemcomitans leukotoxinR00DE022795 · NIDCR · LEHIGH UNIVERSITY · PI BROWN, ANGELA C. · 2014 to 2016
$838k
NEI NIH HHS P30 EY001583NIDCR NIH HHS NIH R00DE022795NIDCR NIH HHS R00 DE022795NIDCR NIH HHS R01 DE009517NIDCR NIH HHS R01DE009517NIDCR NIH HHS R01 DE022465NIDCR NIH HHS R01DE022465
6 · The paper itself

Abstract

The leukotoxin (LtxA) produced by Aggregatibacter actinomycetemcomitans kills host immune cells, allowing the bacterium to establish an ecological niche in the upper aerodigestive tract of its human host. The interaction of LtxA with human immune cells is both complex and multifaceted, involving membrane lipids as well as cell-surface proteins. In the initial encounter with the host cell, LtxA associates with lymphocyte function-associated antigen-1, a cell surface adhesion glycoprotein. However, we have also demonstrated that the toxin associates strongly with the plasma membrane lipids, specifically cholesterol. This association with cholesterol is regulated by a cholesterol recognition amino acid consensus (CRAC) motif, with a sequence of (334) LEEYSKR(340), in the N-terminal region of the toxin. Here, we have demonstrated that removal of cholesterol from the plasma membrane or mutation of the LtxA CRAC motif inhibits the activity of the toxin in THP-1 cells. To inhibit LtxA activity, we designed a short peptide corresponding to the CRAC(336) motif of LtxA (CRAC(336WT)). This peptide binds to cholesterol and thereby inhibits the toxicity of LtxA in THP-1 cells. Previously, we showed that this peptide inhibits LtxA toxicity against Jn.9 (Jurkat) cells, indicating that peptides derived from the cholesterol-binding site of LtxA may have a potential clinical applicability in controlling infections of repeats-in-toxin-producing organisms.

Indexed as

Aggregatibacter actinomycetemcomitansBacterial ToxinsCarrier ProteinsCell AdhesionCell MembraneCholesterolExotoxinsHost-Pathogen InteractionsHumansJurkat CellsLipid BilayersLymphocyte Function-Associated Antigen-1MutationPancreatic ElastasePeptidesBacterial ToxinsCarrier ProteinsCholesterolcholesterol-binding proteinExotoxinsleukotoxinLipid BilayersLymphocyte Function-Associated Antigen-1Pancreatic ElastasePeptidesAggregatibacter actinomycetemcomitanscholesterol-bindingcholesterol recognition amino acid consensus motifleukotoxin

Identifiers

PMID26352738
PMCPMC4712104
OpenAlexW2148308868

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.