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Gut Microbes. 2014 Jan-Feb;5(1):15-27. doi: 10.4161/gmic.26854. Epub 2013 Oct 31.

Clostridium difficile binary toxin CDT: mechanism, epidemiology, and potential clinical importance.

Author information

  • 1Loyola University Chicago Stritch School of Medicine; Hines Veterans Affairs Hospital; Hines, IL USA.
  • 2Institute of Public Health Maribor; University of Maribor, Medical Faculty, and Centre of Excellence for Integrated Approaches in Chemistry and Biology of Proteins; Ljubljana, Slovenia.
  • 3Institute of Experimental and Clinical Pharmacology and Toxicology; Albert-Ludwigs-University Freiburg; Freiburg, Germany.

Abstract

Binary toxin (CDT) is frequently observed in Clostridium difficile strains associated with increased severity of C. difficile infection (CDI). CDT belongs to the family of binary ADP-ribosylating toxins consisting of two separate toxin components: CDTa, the enzymatic ADP-ribosyltransferase which modifies actin, and CDTb which binds to host cells and translocates CDTa into the cytosol. CDTb is activated by serine proteases and binds to lipolysis stimulated lipoprotein receptor. ADP-ribosylation induces depolymerization of the actin cytoskeleton. Toxin-induced actin depolymerization also produces microtubule-based membrane protrusions which form a network on epithelial cells and increase bacterial adherence. Multiple clinical studies indicate an association between binary toxin genes in C. difficile and increased 30-d CDI mortality independent of PCR ribotype. Further studies including measures of binary toxin in stool, analyses of CDI mortality caused by CDT-producing strains, and examination of the relationship of CDT expression to TcdA and TcdB toxin variants and PCR ribotypes are needed.

KEYWORDS:

CDT; Clostridium difficileinfection; PCR ribotyping; binary toxin; disease severity; mechanism; mortality; toxinotyping

PMID:
24253566
[PubMed - in process]
PMCID:
PMC4049931
[Available on 2015/1/1]
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