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