Super toxins from a super bug: structure and function of Clostridium difficile toxins

Abigail H Davies, A K Roberts, C C Shone, K Ravi Acharya

Research output: Contribution to journalArticlepeer-review

58 Citations (Scopus)

Abstract

Clostridium difficile, a highly infectious bacterium, is the leading cause of antibiotic-associated pseudomembranous colitis. In 2009, the number of death certificates mentioning C. difficile infection in the U.K. was estimated at 3933 with 44% of certificates recording infection as the underlying cause of death. A number of virulence factors facilitate its pathogenicity, among which are two potent exotoxins; Toxins A and B. Both are large monoglucosyltransferases that catalyse the glucosylation, and hence inactivation, of Rho-GTPases (small regulatory proteins of the eukaryote actin cell cytoskeleton), leading to disorganization of the cytoskeleton and cell death. The roles of Toxins A and B in the context of C. difficile infection is unknown. In addition to these exotoxins, some strains of C. difficile produce an unrelated ADP-ribosylating binary toxin. This toxin consists of two independently produced components: an enzymatic component (CDTa) and the other, the transport component (CDTb) which facilitates translocation of CDTa into target cells. CDTa irreversibly ADP-ribosylates G-actin in target cells, which disrupts the F-actin:G-actin equilibrium leading to cell rounding and cell death. In the present review we provide a summary of the current structural understanding of these toxins and discuss how it may be used to identify potential targets for specific drug design.
Original languageEnglish
Pages (from-to)517-526
Number of pages10
JournalBiochemical Journal
Volume436
Issue number3
DOIs
Publication statusPublished - 15 Jun 2011

Keywords

  • ADP-ribosyltransferase (ADPRT)
  • Toxin A (TcdA)
  • Toxin B (TcdB)
  • Clostridium difficile binary toxin (CDT)
  • pseudomembranous colitis (PMC)
  • large clostridial toxin (LCT)

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