title: Clostridium difficile binary toxin CDT: mechanism, epidemiology, and potential clinical importance.
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.
authors.affiliation: Loyola University Chicago Stritch School of Medicine; Hines Veterans Affairs Hospital; Hines, IL USA.
authors.forename: Dale N
authors.initials: DN
authors.lastname: Gerding
authors.affiliation: Loyola University Chicago Stritch School of Medicine; Hines Veterans Affairs Hospital; Hines, IL USA.
authors.forename: Stuart
authors.initials: S
authors.lastname: Johnson
authors.affiliation: Institute of Public Health Maribor; University of Maribor, Medical Faculty, and Centre of Excellence for Integrated Approaches in Chemistry and Biology of Proteins; Ljubljana, Slovenia.
authors.forename: Maja
authors.initials: M
authors.lastname: Rupnik
authors.affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology; Albert-Ludwigs-University Freiburg; Freiburg, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Aktories
mesh_terms: D036002:ADP Ribose Transferases / Q000235:genetics / Q000378:metabolism* / Q000633:toxicity; D000199:Actins / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism* / Q000633:toxicity; D016360:Clostridioides difficile / Q000235:genetics / Q000378:metabolism*; D003015:Clostridium Infections / Q000453:epidemiology / Q000378:metabolism / Q000382:microbiology*; D006801:Humans
chemical_list: D000199:Actins; D001426:Bacterial Proteins; D036002:ADP Ribose Transferases; C410164:actin-specific ADP-ribosyltransferase, Clostridium
keywords: CDT; Clostridium difficileinfection; PCR ribotyping; binary toxin; disease severity; mechanism; mortality; toxinotyping