Caister Academic Press

The Toxins of Clostridium difficile

Glen P. Carter, Milena M. Awad, Julian I. Rood and Dena Lyras
from: Bacterial Toxins: Genetics, Cellular Biology and Practical Applications (Edited by: Thomas Proft). Caister Academic Press, U.K. (2013)

Abstract

Clostridium difficile infections represent a range of antibiotic-associated diarrhoea syndromes that are caused by the Gram-positive, spore-forming anaerobe C. difficile. This bacterium is the most significant cause of hospital-acquired diarrhoea in many countries and the emergence of variant strains with enhanced virulence capacity over the last decade has intensified this problem, resulting in major worldwide epidemics. Upon colonisation of a susceptible host C. difficile produces two large clostridial cytotoxins, toxin A (TcdA) and toxin B (TcdB), which are monoglucosyltransferases that irreversibly modify members of the Rho family of host regulatory proteins, leading to disruption of downstream signalling pathways and cell death, with disease manifesting as diarrhoea. Recent studies have indicated that toxin B plays a much more important role in disease than early studies had suggested. Comparison of the more recent epidemic isolates with historical strains has identified numerous differences that may contribute to increased virulence, including the production of binary toxin (CDT), which is an actin-specific ADP-ribosyltransferase. However, the role of CDT in disease pathogenesis remains unclear. This review will discuss our current understanding of the role of the C. difficile toxins in disease, with a particular emphasis on results obtained from studying these toxins using animal disease models read more ...
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