tailieunhanh - Báo cáo khoa học: Molecular basis of toxicity of Clostridium perfringens epsilon toxin

Clostridium perfringense-toxin is produced by toxinotypes B and D strains. The toxin is the aetiological agent of dysentery in newborn lambs but is also associated with enteritis and enterotoxaemia in goats, calves and foals. It is considered to be a potential biowarfare or bioterrorism agent by the US Government Centers for Disease Control and Prevention. | fFEBS Journal REVIEW ARTICLE Molecular basis of toxicity of Clostridium perfringens epsilon toxin Monika Bokori-Brown1 Christos G. Savva2 Sergio P. Fernandes da Costa1 Claire E. Naylor2 Ajit K. Basak2 and Richard W. Titball1 1 Biosciences College of Life and EnvironmentalSciences University of Exeter UK 2 Department of BiologicalSciences Institute of Structuraland Molecular Biology Birkbeck College London UK Keywords Clostridium perfringens crystal structure enterotoxaemia epsilon toxin pore-forming Correspondence R. W. Titball Biosciences College of Life and EnvironmentalSciences Geoffrey Pope Building University of Exeter Stocker Road Exeter EX4 4QD UK Fax 44 0 1392 723 434 Tel 44 0 1392 725 157 E-mail Received 28 February 2011 revised 14 April 2011 accepted 18 April 2011 doi Clostridium perfringens e-toxin is produced by toxinotypes B and D strains. The toxin is the aetiological agent of dysentery in newborn lambs but is also associated with enteritis and enterotoxaemia in goats calves and foals. It is considered to be a potential biowarfare or bioterrorism agent by the US Government Centers for Disease Control and Prevention. The relatively inactive kDa prototoxin is converted to active mature toxin by proteolytic cleavage either by digestive proteases of the host such as trypsin and chymotrypsin or by C. perfringens k-protease. In vivo the toxin appears to target the brain and kidneys but relatively few cell lines are susceptible to the toxin and most work has been carried out using Madin-Darby canine kidney MDCK cells. The binding of e-toxin to MDCK cells and rat synaptosomal membranes is associated with the formation of a stable high molecular weight complex. The crystal structure of e-toxin reveals similarity to aerolysin from Aeromonas hydrophila parasporin-2 from Bacillus thuringiensis and a lectin from Laetiporus sulphureus. Like these toxins e-toxin appears to form heptameric pores in target