Molecular Mechanisms of Action of the Large Clostridial Cytotoxins

  • I. Just
  • F. Hofmann
  • K. Aktories
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 145)


The family of large clostridial cytotoxins consists of toxin A and toxin B from Clostridium difficile, the lethal toxin and the haemorrhagic toxin from C. sordellii, and the α toxin from C. novyi (Table 1). The comparable cytotoxic activities and the similar structures of the toxin molecules have led researchers to group them as one family (Bette et al. 1991). This former phenomenological classification has turned out to be correct because of their almost identical enzymatic ability to modify comparable target proteins. The in vivo effects of the toxins, however, differ from each other; they are major pathogenic factors that cause different diseases and clinical outcomes. Clinically most important is C. difficile,which co-produces toxins A and B, both causally involved in antibiotic-associated diarrhoea and the severe form, pseudomembranous colitis (Bartlett 1994; Kelly et al. 1994; Kelly and Lamont 1998). Lethal toxin from C. sordellii is involved in diarrhoea and enterotoxaemia in domestic animals and in gas gangrene in man (Hatheway 1990). C. novyi a toxin has been identified as causative agent for gas-gangrene infections in man and animals (Harlieway 1990). The divergence between comparable cytotoxic features of the cytotoxin family and differences in clinical features may be due to the presence of additional pathogenic factors and the targeting of different organs by the toxin-producing bacteria. Here we will focus on the cytotoxic (i.e. in vitro) effects of the toxins.


Clostridium Difficile Lethal Toxin ToxinA Alpha Guanosine Diphosphate Glucosyltransferase Activity 
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  • I. Just
  • F. Hofmann
  • K. Aktories

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