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, Vol. 5, 01.01.2015, p. 7850.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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 -