title: Clostridium difficile Toxins A and B: Insights into Pathogenic Properties and Extraintestinal Effects.
abstract: Clostridium difficile infection (CDI) has significant clinical impact especially on the elderly and/or immunocompromised patients. The pathogenicity of Clostridium difficile is mainly mediated by two exotoxins: toxin A (TcdA) and toxin B (TcdB). These toxins primarily disrupt the cytoskeletal structure and the tight junctions of target cells causing cell rounding and ultimately cell death. Detectable C. difficile toxemia is strongly associated with fulminant disease. However, besides the well-known intestinal damage, recent animal and in vitro studies have suggested a more far-reaching role for these toxins activity including cardiac, renal, and neurologic impairment. The creation of C. difficile strains with mutations in the genes encoding toxin A and B indicate that toxin B plays a major role in overall CDI pathogenesis. Novel insights, such as the role of a regulator protein (TcdE) on toxin production and binding interactions between albumin and C. difficile toxins, have recently been discovered and will be described. Our review focuses on the toxin-mediated pathogenic processes of CDI with an emphasis on recent studies.
authors.affiliation: 2nd Infectious Diseases Division, National Institute for Infectious Diseases "L. Spallanzani", Rome 00149, Italy. stefano932@gmail.com.
authors.forename: Stefano
authors.initials: S
authors.lastname: Di Bella
authors.affiliation: Department of Science, Roma Tre University, Rome 00154, Italy. paolo.ascenzi@uniroma3.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Ascenzi
authors.affiliation: Department of Microbiology and Infectious Diseases, Concord Repatriation General Hospital, Sydney 2139, Australia. steven.siarakas@sswahs.nsw.gov.au.
authors.forename: Steven
authors.initials: S
authors.lastname: Siarakas
authors.affiliation: 2nd Infectious Diseases Division, National Institute for Infectious Diseases "L. Spallanzani", Rome 00149, Italy. nicola.petrosillo@inmi.it.
authors.forename: Nicola
authors.initials: N
authors.lastname: Petrosillo
authors.affiliation: Department of Science, Roma Tre University, Rome 00154, Italy. alessandra.dimasi@uniroma3.it.
authors.forename: Alessandra
authors.initials: A
authors.lastname: di Masi
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000633:toxicity; D001427:Bacterial Toxins / Q000737:chemistry / Q000235:genetics / Q000633:toxicity; D003015:Clostridium Infections; D004768:Enterotoxins / Q000737:chemistry / Q000235:genetics / Q000633:toxicity; D006801:Humans; D014115:Toxemia
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004768:Enterotoxins; C041348:tcdA protein, Clostridium difficile; C031815:toxB protein, Clostridium difficile
keywords: Clostridium difficile; pathogenesis; toxins