Clostridium difficile is a species of Gram-positive bacteria that causes diarrhea and other intestinal disease when competing bacteria in the gut flora. It thrives when healthy bacteria in the gut are weakened by antibiotics. Approximately 2 % of all patients admitted to hospital may be infected by C. difficile.
Researchers around Dr. Kenneth Ng and Dr. Glen Armstrong, University of Calgary, Canada, and Dr. Jamshid Tanha, National Research Council, Ottawa, Canada, have found that relatively simple antibodies isolated from a llama can interfere with the disease-causing toxins from C. difficile.
Camelids, which include llamas and camels, produce conventional antibodies found in all mammals as well as heavy-chain antibodies from which single-domain antibodies are derived. These single-chain antibodies are 10 times smaller than those found in humans and can be more readily engineered into a drug.
C. difficile produces two toxins – toxin A (TcdA) and toxin B (TcdB) – which cause damage to intestinal cells by binding to carbohydrates on the cell surface and disrupting cell functions such as adhesion.
Recombinant single-domain antibody fragments (VHHs), which specifically target the cell receptor binding domains of TcdA or TcdB, were isolated from an immune llama phage display library and characterized. Four VHHs were tested as potent neutralizers of the cytopathic effects of toxin A on fibroblast cells in an in vitro assay.
Licensing opportunities with biotechnology firms are being explored. Understanding of why these antibodies are successful will allow researchers to develop new treatments.
- Neutralization of Clostridium difficile toxin A with single-domain antibodies targeting the cell-receptor binding domain,
Greg Hussack, Mehdi Arbabi-Ghahroudi, Henk van Faassen, Glen Songer, Kenneth K.-S Ng, Roger MacKenzie, Jamshid Tanhan,
J. Biol. Chem. 2011.
DOI: 10.1074/jbc.M110.198754
