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


Reference:

Davies, A. H., Roberts, A. K., Shone, C. C. and Acharya, K. R., 2011. Super toxins from a super bug: structure and function of Clostridium difficile toxins. Biochemical Journal, 436 (3), pp. 517-526.

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Official URL:

http://dx.doi.org/10.1042/bj20110106

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.

Details

Item Type Articles
CreatorsDavies, A. H., Roberts, A. K., Shone, C. C. and Acharya, K. R.
DOI10.1042/bj20110106
Uncontrolled Keywordsadp-ribosyltransferase (adprt), toxin a (tcda), toxin b (tcdb), clostridium difficile binary toxin (cdt), pseudomembranous colitis (pmc), large clostridial toxin (lct)
DepartmentsFaculty of Science > Biology & Biochemistry
RefereedYes
StatusPublished
ID Code24968

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