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dc.contributor.author
Unger, Mandy
dc.contributor.author
Eichhoff, Anna Marei
dc.contributor.author
Schumacher, Lucas
dc.contributor.author
Strysio, Moritz
dc.contributor.author
Menzel, Stephan
dc.contributor.author
Schwan, Carsten
dc.contributor.author
Alzogaray, Vanina Andrea
dc.contributor.author
Zylberman, Vanesa
dc.contributor.author
Seman, Michel
dc.contributor.author
Brandner, Johanna
dc.contributor.author
Rohde, Holger
dc.contributor.author
Zhu, Kai
dc.contributor.author
Haag, Friedrich
dc.contributor.author
Mittrücker, Hans Willi
dc.contributor.author
Goldbaum, Fernando Alberto
dc.contributor.author
Aktories, Klaus
dc.contributor.author
Koch Nolte, Friedrich
dc.date.available
2019-10-10T18:01:53Z
dc.date.issued
2015-01
dc.identifier.citation
Unger, Mandy; Eichhoff, Anna Marei; Schumacher, Lucas; Strysio, Moritz; Menzel, Stephan; et al.; Selection of nanobodies that block the enzymatic and cytotoxic activities of the binary clostridium difficile toxin CDT; Nature Publishing Group; Scientific Reports; 5; 7850; 1-2015; 1-10
dc.identifier.issn
2045-2322
dc.identifier.uri
http://hdl.handle.net/11336/85553
dc.description.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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Nature Publishing Group
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
VHH
dc.subject
Clostridium Difficile Toxin
dc.subject
phage display libraries
dc.subject
diagnostic
dc.subject.classification
Bioquímica y Biología Molecular
dc.subject.classification
Ciencias Biológicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
dc.title
Selection of nanobodies that block the enzymatic and cytotoxic activities of the binary clostridium difficile toxin CDT
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2019-10-08T12:07:09Z
dc.journal.volume
5
dc.journal.number
7850
dc.journal.pagination
1-10
dc.journal.pais
Estados Unidos
dc.description.fil
Fil: Unger, Mandy. University Medical Center Hamburg Eppendorf; Alemania
dc.description.fil
Fil: Eichhoff, Anna Marei. University Medical Center Hamburg Eppendorf; Alemania
dc.description.fil
Fil: Schumacher, Lucas. University Medical Center Hamburg Eppendorf; Alemania
dc.description.fil
Fil: Strysio, Moritz. University Medical Center Hamburg Eppendorf; Alemania
dc.description.fil
Fil: Menzel, Stephan. University Medical Center Hamburg Eppendorf; Alemania
dc.description.fil
Fil: Schwan, Carsten. University of Freiburg; Alemania
dc.description.fil
Fil: Alzogaray, Vanina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Instituto Leloir; Argentina
dc.description.fil
Fil: Zylberman, Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Inmunova S.A; Argentina
dc.description.fil
Fil: Seman, Michel. Normandy University; Francia
dc.description.fil
Fil: Brandner, Johanna. University Medical Center Hamburg Eppendorf; Alemania
dc.description.fil
Fil: Rohde, Holger. University Medical Center Hamburg Eppendorf; Alemania
dc.description.fil
Fil: Zhu, Kai. Schrodinger Inc.; Estados Unidos
dc.description.fil
Fil: Haag, Friedrich. University Medical Center Hamburg Eppendorf; Alemania
dc.description.fil
Fil: Mittrücker, Hans Willi. University Medical Center Hamburg Eppendorf; Alemania
dc.description.fil
Fil: Goldbaum, Fernando Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Instituto Leloir; Argentina
dc.description.fil
Fil: Aktories, Klaus. University of Freiburg; Alemania
dc.description.fil
Fil: Koch Nolte, Friedrich. University Medical Center Hamburg Eppendorf; Alemania
dc.journal.title
Scientific Reports
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1038/srep07850
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/srep07850
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