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Toxins 2018, 10(6), 225; https://doi.org/10.3390/toxins10060225

The Binary Toxin CDT of Clostridium difficile as a Tool for Intracellular Delivery of Bacterial Glucosyltransferase Domains

1
Institute of Toxicology, Hannover Medical School, 30625 Hannover, Germany
2
Department of Biochemistry and Biotechnology, Technical University Braunschweig, 38106 Braunschweig, Germany
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 9 April 2018 / Revised: 28 May 2018 / Accepted: 30 May 2018 / Published: 1 June 2018
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Abstract

Binary toxins are produced by several pathogenic bacteria. Examples are the C2 toxin from Clostridium botulinum, the iota toxin from Clostridium perfringens, and the CDT from Clostridium difficile. All these binary toxins have ADP-ribosyltransferases (ADPRT) as their enzymatically active component that modify monomeric actin in their target cells. The binary C2 toxin was intensively described as a tool for intracellular delivery of allogenic ADPRTs. Here, we firstly describe the binary toxin CDT from C. difficile as an effective tool for heterologous intracellular delivery. Even 60 kDa glucosyltransferase domains of large clostridial glucosyltransferases can be delivered into cells. The glucosyltransferase domains of five tested large clostridial glucosyltransferases were successfully introduced into cells as chimeric fusions to the CDTa adapter domain (CDTaN). Cell uptake was demonstrated by the analysis of cell morphology, cytoskeleton staining, and intracellular substrate glucosylation. The fusion toxins were functional only when the adapter domain of CDTa was N-terminally located, according to its native orientation. Thus, like other binary toxins, the CDTaN/b system can be used for standardized delivery systems not only for bacterial ADPRTs but also for a variety of bacterial glucosyltransferase domains. View Full-Text
Keywords: binary toxins; Clostridium difficile; ADP-ribosyltransferase; glucosyltransferase; protein delivery binary toxins; Clostridium difficile; ADP-ribosyltransferase; glucosyltransferase; protein delivery
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Beer, L.-A.; Tatge, H.; Schneider, C.; Ruschig, M.; Hust, M.; Barton, J.; Thiemann, S.; Fühner, V.; Russo, G.; Gerhard, R. The Binary Toxin CDT of Clostridium difficile as a Tool for Intracellular Delivery of Bacterial Glucosyltransferase Domains. Toxins 2018, 10, 225.

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