The roles of toxin A and toxin B in Clostridium difficile infection

Abstract

We recently published our findings indicating that anti-TcdB antibodies were effective as treatment for C. difficile infection, but that anti-TcdA actually worsened prognosis in the gnotobiotic piglet model. To further investigate the roles of the two toxins, we administered purified toxins separately or together, systemically, to piglets and found that both toxins, either alone or together, are able to elicit severe lesions systemically and are also able to cross into the gut lumen and cause large intestinal lesions typical of infection. We also found that anti-TcdA administered before systemic challenge with TcdA again did not protect from development of disease, but, in this case, did not appear to worsen prognosis. Further work is still needed, but these findings add to the growing knowledge regarding the roles of the C. difficile toxins.

Keywords: :

• Clostridium difficile
• TcdA
• TcdB
• toxins
• systemic toxins
• toxemia
• anti-toxin antibodies
• monoclonal antibodies

This article refers to:

10.4161/gmic.26855

Disclosure of Potential Conflicts of Interest

No potential conflict of interest was disclosed.

Acknowledgments

We would like to thank our animal technical staff members, Patricia Boucher and Rachel Nieminen, for providing care to the animals and assistance with these experiments. We also thank Merck, Inc for providing grant support and the monoclonal antibodies used in this work.

Funding

This work was supported by Merck, Inc grant LKR8118, and National Institutes of Health Grants F32AI081497, R56AI094459, and R01AI088748.