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Retargeting Clostridium difficile Toxin B to Neuronal Cells as a Potential Vehicle for Cytosolic Delivery of Therapeutic Biomolecules to Treat Botulism
Joint Authors
Oyler, George A.
Shoemaker, Charles B.
Feng, Hanping
Zhang, Yongrong
Krautz-Peterson, Greice
Chen, Kevin
Source
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-9, 9 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2011-09-20
Country of Publication
Egypt
No. of Pages
9
Main Subjects
Pharmacy, Health & Medical Sciences
Medicine
Abstract EN
Botulinum neurotoxins (BoNTs) deliver a protease to neurons which can cause a flaccid paralysis called botulism.
Development of botulism antidotes will require neuronal delivery of agents that inhibit or destroy the BoNT protease.
Here, we investigated the potential of engineering Clostridium difficile toxin B (TcdB) as a neuronal delivery vehicle by testing two recombinant TcdB chimeras.
For AGT-TcdB chimera, an alkyltransferase (AGT) was appended to the N-terminal glucosyltransferase (GT) of TcdB.
Recombinant AGT-TcdB had alkyltransferase activity, and the chimera was nearly as toxic to Vero cells as wild-type TcdB, suggesting efficient cytosolic delivery of the AGT/GT fusion.
For AGT-TcdB-BoNT/A-Hc, the receptor-binding domain (RBD) of TcdB was replaced by the equivalent RBD from BoNT/A (BoNT/A-Hc).
AGT-TcdB-BoNT/A-Hc was >25-fold more toxic to neuronal cells and >25-fold less toxic to Vero cells than AGT-TcdB.
Thus, TcdB can be engineered for cytosolic delivery of biomolecules and improved targeting of neuronal cells.
American Psychological Association (APA)
Krautz-Peterson, Greice& Zhang, Yongrong& Chen, Kevin& Oyler, George A.& Feng, Hanping& Shoemaker, Charles B.. 2011. Retargeting Clostridium difficile Toxin B to Neuronal Cells as a Potential Vehicle for Cytosolic Delivery of Therapeutic Biomolecules to Treat Botulism. Journal of Toxicology،Vol. 2012, no. 2012, pp.1-9.
https://search.emarefa.net/detail/BIM-496574
Modern Language Association (MLA)
Krautz-Peterson, Greice…[et al.]. Retargeting Clostridium difficile Toxin B to Neuronal Cells as a Potential Vehicle for Cytosolic Delivery of Therapeutic Biomolecules to Treat Botulism. Journal of Toxicology No. 2012 (2012), pp.1-9.
https://search.emarefa.net/detail/BIM-496574
American Medical Association (AMA)
Krautz-Peterson, Greice& Zhang, Yongrong& Chen, Kevin& Oyler, George A.& Feng, Hanping& Shoemaker, Charles B.. Retargeting Clostridium difficile Toxin B to Neuronal Cells as a Potential Vehicle for Cytosolic Delivery of Therapeutic Biomolecules to Treat Botulism. Journal of Toxicology. 2011. Vol. 2012, no. 2012, pp.1-9.
https://search.emarefa.net/detail/BIM-496574
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-496574