Clostridial toxins: Sensing a target in a hostile gut environment

Numan Oezguen, Trevor D. Power, Petri Urvil, Hanping Feng, Charalabos Pothoulakis, Jonathan S. Stamler, Werner Braun, Tor C. Savidge

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

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.

Original languageEnglish (US)
JournalGut Microbes
Volume3
Issue number1
StatePublished - Jan 1 2012

Keywords

  • Allostery
  • C. difficile
  • Dietary supplement
  • Inositol phosphate
  • S-nitrosylation
  • Toxin

ASJC Scopus subject areas

  • Microbiology
  • Gastroenterology
  • Microbiology (medical)
  • Infectious Diseases

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  • Cite this

    Oezguen, N., Power, T. D., Urvil, P., Feng, H., Pothoulakis, C., Stamler, J. S., Braun, W., & Savidge, T. C. (2012). Clostridial toxins: Sensing a target in a hostile gut environment. Gut Microbes, 3(1).