Evidence map›Paper›PMID 25597743›Full record

ArticleScientific reports2015

Selection of nanobodies that block the enzymatic and cytotoxic activities of the binary Clostridium difficile toxin CDT.

Mandy Unger, Anna Marei Eichhoff, Lucas Schumacher, Moritz Strysio, Stephan Menzel, Carsten Schwan, Vanina Alzogaray, Vanesa Zylberman, Michel Seman, Johanna Brandner and 7 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
4.3field-weighted citation impact, top 5% 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

40 citing papers in PubMed, 69 citations in OpenAlex.

  1. Article
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  9. Immunization Strategies Against Clostridioides difficile.Advances in experimental medicine and biology · 2024
    Review
  10. Review
  11. Targeting the Inside of Cells with Biologicals: Toxin Routes in a Therapeutic Context.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023
    Review
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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

17 authors at 4 institutions in 2 countries.

Mandy UngerInstitute of Immunology, University Medical Center Hamburg-Eppendorf, Germany.
Anna Marei EichhoffInstitute of Immunology, University Medical Center Hamburg-Eppendorf, Germany.
Lucas SchumacherInstitute of Immunology, University Medical Center Hamburg-Eppendorf, Germany.
Moritz StrysioInstitute of Immunology, University Medical Center Hamburg-Eppendorf, Germany.
Stephan MenzelInstitute of Immunology, University Medical Center Hamburg-Eppendorf, Germany.
Carsten SchwanInstitute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg, Germany.
Vanina AlzogarayFundacion Instituto Leloir, C1405 Buenos Aires, Argentina.
Vanesa ZylbermanInmunova, C1405 Buenos Aires, Argentina.
Michel SemanNormandy University, Institute for Research and Innovation in Biomedicine, 76183 Rouen, France.
Johanna BrandnerDepartment of Dermatology, University Medical Center Hamburg-Eppendorf, Germany.
Holger RohdeInstitute of Microbiology, University Medical Center Hamburg-Eppendorf, Germany.
Kai ZhuSchrodinger Inc., 120 West 45th Street, New York, New York 10036, United States.
Friedrich HaagInstitute of Immunology, University Medical Center Hamburg-Eppendorf, Germany.
Hans-Willi MittrückerInstitute of Immunology, University Medical Center Hamburg-Eppendorf, Germany.
Fernando GoldbaumFundacion Instituto Leloir, C1405 Buenos Aires, Argentina.
Klaus AktoriesInstitute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg, Germany.
Friedrich Koch-NolteInstitute of Immunology, University Medical Center Hamburg-Eppendorf, Germany.
University Medical Center Hamburg-Eppendorf · DEUniversität Hamburg · DEUniversity of Freiburg · DESchrodinger (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The spore-forming gut bacterium Clostridium difficile is the leading cause of antibiotic-associated diarrhea in hospitalized patients. The major virulence factors are two large glucosylating cytotoxins. Hypervirulent strains (e.g. ribotype 027) with higher morbidity and mortality additionally produce the binary CDT toxin (Clostridium difficile transferase) that ADP-ribosylates actin and induces microtubule-based cell protrusions. Nanobodies are robust single domain antibodies derived from camelid heavy chain antibodies. Here we report the generation of functional nanobodies against the enzymatic CDTa and the heptameric receptor binding subunit CDTb. The nanobodies were obtained from a variable-domain repertoire library isolated from llamas immunized with recombinant CDTa or CDTb. Five CDTa-specific nanobodies blocked CDTa-mediated ADP-ribosylation of actin. Three CDTa-specific and two CDTb-specific nanobodies neutralized the cytotoxicity of CDTa+b. These nanobodies hold promise as new tools for research, diagnosis and therapy of C. difficile associated disease.

Indexed as

ActinsADP Ribose TransferasesAmino Acid SequenceAnimalsAntibodies, NeutralizingBacterial ProteinsCell SurvivalClostridioides difficileDogsEpitope MappingEpitopesHT29 CellsHumansMadin Darby Canine Kidney CellsMicroscopy, InterferenceMolecular Sequence DataActinsactin-specific ADP-ribosyltransferase, ClostridiumADP Ribose TransferasesAntibodies, NeutralizingBacterial ProteinsEpitopesProtein SubunitsRecombinant ProteinsSingle-Domain Antibodies

Identifiers

PMID25597743
PMCPMC4297958
OpenAlexW2083669011

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.