Retargeting Clostridium difficile Toxin B to Neuronal Cells as a Potential Vehicle for Cytosolic Delivery of Therapeutic Biomolecules to Treat Botulism
2012

Using Clostridium difficile Toxin B to Deliver Treatments for Botulism

publication Evidence: moderate

Author Information

Author(s): Greice Krautz-Peterson, Yongrong Zhang, Kevin Chen, George A. Oyler, Hanping Feng, Charles B. Shoemaker

Primary Institution: Tufts Cummings School of Veterinary Medicine

Hypothesis

Can Clostridium difficile toxin B be engineered to deliver therapeutic biomolecules specifically to neuronal cells?

Conclusion

The study shows that engineered Clostridium difficile toxin B can effectively deliver therapeutic agents to neuronal cells, potentially serving as a treatment for botulism.

Supporting Evidence

  • Recombinant AGT-TcdB was nearly as toxic to Vero cells as wild-type TcdB, indicating effective delivery.
  • AGT-TcdB-BoNT/A-Hc was over 25-fold more toxic to neuronal cells compared to AGT-TcdB.
  • The presence of the BoNT/A-Hc domain improved the potency of the toxin for neuronal cells.
  • AGT-TcdB retained enzymatic activity, demonstrating its potential as a delivery vehicle.

Takeaway

Scientists are trying to use a toxin from bacteria to help deliver medicine directly to brain cells that are affected by another toxin that causes paralysis.

Methodology

The study involved engineering two chimeric forms of Clostridium difficile toxin B and testing their toxicity on various cell lines.

Limitations

The engineered toxins still retained some toxicity to non-neuronal cells, which may limit their therapeutic use.

Digital Object Identifier (DOI)

10.1155/2012/760142

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