Evidence map›Paper›PMID 26216427›Full record

ArticleInfection and immunity2015

The Aggregatibacter actinomycetemcomitans Cytolethal Distending Toxin Active Subunit CdtB Contains a Cholesterol Recognition Sequence Required for Toxin Binding and Subunit Internalization.

Kathleen Boesze-Battaglia, Lisa P Walker, Ali Zekavat, Mensur Dlakić, Monika Damek Scuron, Patrik Nygren, Bruce J Shenker

Open access · bronzeAbstract read
In one paragraph

Article in Infection and immunity, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

16 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
  2. Pathogens (Basel, Switzerland) · 2024
    Article
  3. Article
  4. International journal of molecular sciences · 2022
    Article
  5. The Active Subunit of the Cytolethal Distending Toxin, CdtB, Derived From BothFrontiers in cellular and infection microbiology · 2021
    Article
  6. Article
  7. Article
  8. Review
  9. Internalization of the Active Subunit of theFrontiers in cellular and infection microbiology · 2017
    Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Review
  16. A Journey of Cytolethal Distending Toxins through Cell Membranes.Frontiers in cellular and infection microbiology · 2016
    Review
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

7 authors at 3 institutions in 2 countries.

Kathleen Boesze-BattagliaDepartment of Biochemistry, University of Pennsylvania School of Dental Medicine, Philadelphia, Pennsylvania, USA.
Lisa P WalkerDepartment of Pathology, University of Pennsylvania School of Dental Medicine, Philadelphia, Pennsylvania, USA.
Ali ZekavatDepartment of Pathology, University of Pennsylvania School of Dental Medicine, Philadelphia, Pennsylvania, USA.
Mensur DlakićDepartment of Microbiology and Immunology, Montana State University, Bozeman, Montana, USA.
Monika Damek ScuronDepartment of Pathology, University of Pennsylvania School of Dental Medicine, Philadelphia, Pennsylvania, USA.
Patrik NygrenDivisions of Molecular Surface Physics and Nanoscience and Molecular Physics, Linköping University, Linköping, Sweden.
Bruce J ShenkerDepartment of Pathology, University of Pennsylvania School of Dental Medicine, Philadelphia, Pennsylvania, USA shenker@upenn.edu.
University of Pennsylvania · USLinköping University · SEMontana State University · US

Funding

BACTERIA &LYMPHOCYTE SUPPRESSION IN PERIODONTITISR01DE006014 · NIDCR · UNIVERSITY OF PENNSYLVANIA · PI SHENKER, BRUCE J · 1985 to 2021
$8.6M
A. Actinomycetemcomitans Cdt Induces Pro-Inflammatory Innate Immune ResponsesR01DE023071 · NIDCR · UNIVERSITY OF PENNSYLVANIA · PI BOESZE-BATTAGLIA, KATHLEEN, SHENKER, BRUCE J · 2013 to 2024
$4.6M
NIDCR NIH HHS DE023071NIDCR NIH HHS DE06014NIDCR NIH HHS R01 DE006014NIDCR NIH HHS R01 DE023071
6 · The paper itself

Abstract

Induction of cell cycle arrest in lymphocytes following exposure to the Aggregatibacter actinomycetemcomitans cytolethal distending toxin (Cdt) is dependent upon the integrity of lipid membrane microdomains. Moreover, we have previously demonstrated that the association of Cdt with target cells involves the CdtC subunit which binds to cholesterol via a cholesterol recognition amino acid consensus sequence (CRAC site). In this study, we demonstrate that the active Cdt subunit, CdtB, also is capable of binding to large unilamellar vesicles (LUVs) containing cholesterol. Furthermore, CdtB binding to cholesterol involves a similar CRAC site as that demonstrated for CdtC. Mutation of the CRAC site reduces binding to model membranes as well as toxin binding and CdtB internalization in both Jurkat cells and human macrophages. A concomitant reduction in Cdt-induced toxicity was also noted, indicated by reduced cell cycle arrest and apoptosis in Jurkat cells and a reduction in the proinflammatory response in macrophages (interleukin 1β [IL-1β] and tumor necrosis factor alpha [TNF-α] release). Collectively, these observations indicate that membrane cholesterol serves as an essential ligand for both CdtC and CdtB and, further, that this binding is necessary for both internalization of CdtB and subsequent molecular events leading to intoxication of cells.

Indexed as

Aggregatibacter actinomycetemcomitansAmino Acid MotifsBacterial ToxinsCholesterolHumansInterleukin-1betaMacrophagesPasteurellaceae InfectionsTumor Necrosis Factor-alphaBacterial ToxinsCholesterolcytolethal distending toxinInterleukin-1betaTumor Necrosis Factor-alpha

Identifiers

PMID26216427
PMCPMC4567645
OpenAlexW2122679010

What Socratic 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 Socratic graph.