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Selection of Nanobodies that Block the Enzymatic and Cytotoxic Activities of the Binary Clostridium Difficile Toxin CDT

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Selection of Nanobodies that Block the Enzymatic and Cytotoxic Activities of the Binary Clostridium Difficile Toxin CDT. / Unger, Mandy; Eichhoff, Anna Marei; Schumacher, Lucas; Strysio, Moritz; Menzel, Stephan; Schwan, Carsten; Alzogaray, Vanina; Zylberman, Vanesa; Seman, Michel; Brandner, Johanna; Rohde, Holger; Zhu, Kai; Haag, Friedrich; Mittrücker, Hans-Willi; Goldbaum, Fernando; Aktories, Klaus; Nolte, Friedrich.

in: SCI REP-UK, Jahrgang 5, 01.01.2015, S. 7850.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Unger, M, Eichhoff, AM, Schumacher, L, Strysio, M, Menzel, S, Schwan, C, Alzogaray, V, Zylberman, V, Seman, M, Brandner, J, Rohde, H, Zhu, K, Haag, F, Mittrücker, H-W, Goldbaum, F, Aktories, K & Nolte, F 2015, 'Selection of Nanobodies that Block the Enzymatic and Cytotoxic Activities of the Binary Clostridium Difficile Toxin CDT', SCI REP-UK, Jg. 5, S. 7850. https://doi.org/10.1038/srep07850

APA

Unger, M., Eichhoff, A. M., Schumacher, L., Strysio, M., Menzel, S., Schwan, C., Alzogaray, V., Zylberman, V., Seman, M., Brandner, J., Rohde, H., Zhu, K., Haag, F., Mittrücker, H-W., Goldbaum, F., Aktories, K., & Nolte, F. (2015). Selection of Nanobodies that Block the Enzymatic and Cytotoxic Activities of the Binary Clostridium Difficile Toxin CDT. SCI REP-UK, 5, 7850. https://doi.org/10.1038/srep07850

Vancouver

Unger M, Eichhoff AM, Schumacher L, Strysio M, Menzel S, Schwan C et al. Selection of Nanobodies that Block the Enzymatic and Cytotoxic Activities of the Binary Clostridium Difficile Toxin CDT. SCI REP-UK. 2015 Jan 1;5:7850. https://doi.org/10.1038/srep07850

Bibtex

@article{a7f9d48edf5c472b930af6eb1ebcb84f,
title = "Selection of Nanobodies that Block the Enzymatic and Cytotoxic Activities of the Binary Clostridium Difficile Toxin CDT",
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.",
author = "Mandy Unger and Eichhoff, {Anna Marei} and Lucas Schumacher and Moritz Strysio and Stephan Menzel and Carsten Schwan and Vanina Alzogaray and Vanesa Zylberman and Michel Seman and Johanna Brandner and Holger Rohde and Kai Zhu and Friedrich Haag and Hans-Willi Mittr{\"u}cker and Fernando Goldbaum and Klaus Aktories and Friedrich Nolte",
year = "2015",
month = jan,
day = "1",
doi = "10.1038/srep07850",
language = "English",
volume = "5",
pages = "7850",
journal = "SCI REP-UK",
issn = "2045-2322",
publisher = "NATURE PUBLISHING GROUP",

}

RIS

TY - JOUR

T1 - Selection of Nanobodies that Block the Enzymatic and Cytotoxic Activities of the Binary Clostridium Difficile Toxin CDT

AU - Unger, Mandy

AU - Eichhoff, Anna Marei

AU - Schumacher, Lucas

AU - Strysio, Moritz

AU - Menzel, Stephan

AU - Schwan, Carsten

AU - Alzogaray, Vanina

AU - Zylberman, Vanesa

AU - Seman, Michel

AU - Brandner, Johanna

AU - Rohde, Holger

AU - Zhu, Kai

AU - Haag, Friedrich

AU - Mittrücker, Hans-Willi

AU - Goldbaum, Fernando

AU - Aktories, Klaus

AU - Nolte, Friedrich

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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.

AB - 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.

U2 - 10.1038/srep07850

DO - 10.1038/srep07850

M3 - SCORING: Journal article

C2 - 25597743

VL - 5

SP - 7850

JO - SCI REP-UK

JF - SCI REP-UK

SN - 2045-2322

ER -