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Structural Characterisation of the TcdA Toxin from Clostridium Difficile

Institutions
Imperial College - London
Start date
2001
End date
2004
Objective
The bacterial pathogen Clostridium difficile produces two potent high molecular weight protein toxins, TcdA and TcdB. The C-terminal domain of TcdA is essential for binding to host cells, and contains multiple repeated sequences which interact with carbohydrate ligands. We will express and purify the C-terminal repeat region from E. coli and verify functionality using biological assays including direct binding to host cells and competition of TcdA holotoxin binding. We will then use NMR to obtain the three dimensional structure of the repeat domain, both in its free form and as complexes with glycan analogues of its natural glycosylated receptor. In parallel, we will express other domains of TcdA and TcdB in either E. coli or Lactococcus lactis, and carry out crystallisation trials with purified proteins.
Funding Source
Biotechnology and Biological Sciences Research Council
Project number
B15840
Categories
Natural Toxins
Bacterial Pathogens
Escherichia coli