Clostridial toxins: sensing a target in a hostile gut environment.

Published

Journal Article (Review)

The current global outbreak of Clostridium difficile infection exemplifies the major public health threat posed by clostridial glucosylating toxins. In the western world, C. difficile infection is one of the most prolific causes of bacterial-induced diarrhea and potentially fatal colitis. Two pathogenic enterotoxins, TcdA and TcdB, cause the disease. Vancomycin and metronidazole remain readily available treatment options for C. difficile infection, but neither is fully effective as is evident by high clinical relapse and fatality rates. Thus, there is an urgent need to find an alternative therapy that preferentially targets the toxins and not the drug-resistant pathogen. Recently, we addressed these critical issues in a Nature Medicine letter, describing a novel host defense mechanism for subverting toxin virulence that we translated into prototypic allosteric therapy for C. difficile infection. In this addendum article, we provide a continued perspective of this antitoxin mechanism and consider the broader implications of therapeutic allostery in combating gut microbial pathogenesis.

Full Text

Duke Authors

Cited Authors

  • Oezguen, N; Power, TD; Urvil, P; Feng, H; Pothoulakis, C; Stamler, JS; Braun, W; Savidge, TC

Published Date

  • January 2012

Published In

Volume / Issue

  • 3 / 1

Start / End Page

  • 35 - 41

PubMed ID

  • 22356854

Pubmed Central ID

  • 22356854

Electronic International Standard Serial Number (EISSN)

  • 1949-0984

Digital Object Identifier (DOI)

  • 10.4161/gmic.19250

Language

  • eng

Conference Location

  • United States