Evidence map›Paper›PMID 25029374›Full record

ArticleToxins2014

Tailored cyclodextrin pore blocker protects mammalian cells from clostridium difficile binary toxin CDT.

Maurice Roeder, Ekaterina M Nestorovich, Vladimir A Karginov, Carsten Schwan, Klaus Aktories, Holger Barth

Open access · goldAbstract read
In one paragraph

Article in Toxins, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.8field-weighted citation impact, top 16% 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

8 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
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  4. Review
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  8. Multivalent Inhibitors of Channel-Forming Bacterial Toxins.Current topics in microbiology and immunology
    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

6 authors at 4 institutions in 2 countries.

Maurice RoederInstitute of Pharmacology and Toxicology, University of Ulm Medical Center, Albert-Einstein-Allee 11, 89081 Ulm, Germany. maurice.roeder@uni-ulm.de.
Ekaterina M NestorovichDepartment of Biology, the Catholic University of America, Washington, DC 20064, USA. nestorovich@cua.edu.
Vladimir A KarginovInnovative Biologics, Inc., 13455 Sunrise Valley Dr., Suite 200, Herndon, VA 20171, USA. vak@innovbio.com.
Carsten SchwanInstitute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg, 79104 Freiburg, Germany. carsten.schwan@pharmakol.uni-freiburg.de.
Klaus AktoriesInstitute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg, 79104 Freiburg, Germany. klaus.aktories@pharmakol.uni-freiburg.de.
Holger BarthInstitute of Pharmacology and Toxicology, University of Ulm Medical Center, Albert-Einstein-Allee 11, 89081 Ulm, Germany. holger.barth@uni-ulm.de.
Universität Ulm · DEUniversity of Freiburg · DEInnovative Biologics (United States) · USUniversity of America · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Some Clostridium difficile strains produce, in addition to toxins A and B, the binary toxin Clostridium difficile transferase (CDT), which ADP-ribosylates actin and may contribute to the hypervirulence of these strains. The separate binding and translocation component CDTb mediates transport of the enzyme component CDTa into mammalian target cells. CDTb binds to its receptor on the cell surface, CDTa assembles and CDTb/CDTa complexes are internalised. In acidic endosomes, CDTb mediates the delivery of CDTa into the cytosol, most likely by forming a translocation pore in endosomal membranes. We demonstrate that a seven-fold symmetrical positively charged β-cyclodextrin derivative, per-6-S-(3-aminomethyl)benzylthio-β-cyclodextrin, which was developed earlier as a potent inhibitor of the translocation pores of related binary toxins of Bacillus anthracis, Clostridium botulinum and Clostridium perfringens, protects cells from intoxication with CDT. The pore blocker did not interfere with the CDTa-catalyzed ADP-ribosylation of actin or toxin binding to Vero cells but inhibited the pH-dependent membrane translocation of CDTa into the cytosol. In conclusion, the cationic β-cyclodextrin could serve as the lead compound in a development of novel pharmacological strategies against the CDT-producing strains of C. difficile.

Indexed as

Clostridioides difficileADP Ribose TransferasesAnimalsbeta-CyclodextrinsCell MembraneChlorocebus aethiopsProtective AgentsVero CellsADP Ribose Transferasesbeta-CyclodextrinsProtective Agents

Identifiers

PMID25029374
PMCPMC4113744
OpenAlexW1984571101

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.