Large clostridial cytotoxins

Chapter
Part of the Reviews of Physiology, Biochemistry and Pharmacology book series (REVIEWS, volume 152)

Abstract

The large clostridial cytotoxins are a family of structurally and functionally related exotoxins from Clostridium difficile (toxins A and B), C. sordellii (lethal and hemorrhagic toxin) and C. novyi (α-toxin). The exotoxins are major pathogenicity factors which in addition to their in vivo effects are cytotoxic to cultured cell lines causing reorganization of the cytoskeleton accompanied by morphological changes. The exotoxins are single-chain protein toxins, which are constructed of three domains: receptor-binding, translocation and catalytic domain. These domains reflect the self-mediated cell entry via receptor-mediated endocytosis, translocation into the cytoplasm, and execution of their cytotoxic activity by an inherent enzyme activity. Enzymatically, the toxins catalyze the transfer of a glucosyl moiety from UDP-glucose to the intracellular target proteins which are the Rho and Ras GTPases. The covalent attachment of the glucose moiety to a conserved threonine within the effector region of the GTPases renders the Rho-GTPases functionally inactive. Whereas the molecular mode of cytotoxic effects is fully understood, the mechanisms leading to inflammatory processes in the context of disease (e.g., antibiotic-associated pseudomembranous colitis caused by Clostridium difficile) are less clear.

Abbreviations

CDAD

Clostridium difficile-associated diarrhea

C3

ADP-ribosyltransferase C3 from Clostridium botulinum

LCT

Large clostridial cytotoxin

TcdA

Clostridium difficile toxin A

TcdB

Clostridium difficile toxin B

TcsL

Clostridium sordellii lethal toxin

TcsH

Clostridium sordellii hemorrhagic toxin

TcnA

Clostridium novyi alpha-toxin

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© Springer-Verlag 2004

Authors and Affiliations

  1. 1.Institut für ToxikologieMedizinische Hochschlule HannoverHannoverGermany

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