Oral Presentation BACPATH 2019

Epsilon toxin, Mal and multiple sclerosis (#38)

Richard W Titball 1
  1. University of Exeter, Exeter, DEVON, United Kingdom

Epsilon toxin, a pore forming toxin produced by Clostridium perfringens types B and D strains, is one of the most potent bacterial toxins. The toxin is responsible for the pathogenesis of enterotoxaemia, an often fatal neurological disease of livestock, particularly sheep and goats. A receptor for the toxin has recently been identified as myelin and lymphocyte (MAL) protein. The molecular structures of the monomeric and pore forms of the toxin reveal the mode of action of the toxin and identify how the toxin interacts with MAL. This data has been used to devise a genetic toxoid (Y30A-Y196A-A168F) vaccine. The immunisation of rabbits or sheep with Y30A-Y196A-A168F induced high levels of neutralising antibodies against epsilon toxin which persisted for at least one year. The finding that the toxin recognises MAL has also stimulated work to investigate the possible role of this toxin in multiple sclerosis (MS), and antibodies to the toxin have been found in the sera of some MS patients. However, evidence for a role for the toxin in the MS is not conclusive.