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 Citations (Scopus)

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 2012

Fingerprint

Clostridium Infections
Clostridium difficile
Antitoxins
Western World
Enterotoxins
Metronidazole
Colitis
Vancomycin
Complementary Therapies
Disease Outbreaks
Virulence
Diarrhea
Therapeutics
Public Health
Medicine
Recurrence
Pharmaceutical Preparations

Keywords

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

ASJC Scopus subject areas

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

Cite this

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

Clostridial toxins : Sensing a target in a hostile gut environment. / Oezguen, Numan; Power, Trevor D.; Urvil, Petri; Feng, Hanping; Pothoulakis, Charalabos; Stamler, Jonathan S.; Braun, Werner; Savidge, Tor C.

In: Gut Microbes, Vol. 3, No. 1, 01.2012.

Research output: Contribution to journalArticle

Oezguen, N, Power, TD, Urvil, P, Feng, H, Pothoulakis, C, Stamler, JS, Braun, W & Savidge, TC 2012, 'Clostridial toxins: Sensing a target in a hostile gut environment', Gut Microbes, vol. 3, no. 1.
Oezguen N, Power TD, Urvil P, Feng H, Pothoulakis C, Stamler JS et al. Clostridial toxins: Sensing a target in a hostile gut environment. Gut Microbes. 2012 Jan;3(1).
Oezguen, Numan ; Power, Trevor D. ; Urvil, Petri ; Feng, Hanping ; Pothoulakis, Charalabos ; Stamler, Jonathan S. ; Braun, Werner ; Savidge, Tor C. / Clostridial toxins : Sensing a target in a hostile gut environment. In: Gut Microbes. 2012 ; Vol. 3, No. 1.
@article{3903487c86fc440a972686d76123560c,
title = "Clostridial toxins: Sensing a target in a hostile gut environment",
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.",
keywords = "Allostery, C. difficile, Dietary supplement, Inositol phosphate, S-nitrosylation, Toxin",
author = "Numan Oezguen and Power, {Trevor D.} and Petri Urvil and Hanping Feng and Charalabos Pothoulakis and Stamler, {Jonathan S.} and Werner Braun and Savidge, {Tor C.}",
year = "2012",
month = "1",
language = "English (US)",
volume = "3",
journal = "Gut Microbes",
issn = "1949-0976",
publisher = "Landes Bioscience",
number = "1",

}

TY - JOUR

T1 - Clostridial toxins

T2 - Sensing a target in a hostile gut environment

AU - Oezguen, Numan

AU - Power, Trevor D.

AU - Urvil, Petri

AU - Feng, Hanping

AU - Pothoulakis, Charalabos

AU - Stamler, Jonathan S.

AU - Braun, Werner

AU - Savidge, Tor C.

PY - 2012/1

Y1 - 2012/1

N2 - 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.

AB - 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.

KW - Allostery

KW - C. difficile

KW - Dietary supplement

KW - Inositol phosphate

KW - S-nitrosylation

KW - Toxin

UR - http://www.scopus.com/inward/record.url?scp=84858602079&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84858602079&partnerID=8YFLogxK

M3 - Article

VL - 3

JO - Gut Microbes

JF - Gut Microbes

SN - 1949-0976

IS - 1

ER -