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Detection of Toxin Translocation into the Host Cytosol by Surface Plasmon Resonance
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Published on: January 3, 2012

Glucosylation of Rho proteins by Clostridium difficile toxin B

I Just1, J Selzer, M Wilm

  • 1Institut für Pharmakologie und Toxikologie, Universität des Saarlandes, Homburg/Saar, Germany.

Nature
|June 8, 1995
PubMed

Insights

Clostridium difficile toxin B modifies RhoA GTPase by adding glucose, inactivating it. This glucosylated RhoA disrupts the actin cytoskeleton, causing cell damage and contributing to colitis.

Area of Science:

  • Microbiology
  • Cell Biology
  • Biochemistry

Background:

  • Clostridium difficile toxins A and B cause antibiotic-associated colitis.
  • These toxins induce cytotoxicity by disaggregating the microfilament cytoskeleton.
  • Toxin B targets the RhoA GTPase, crucial for actin cytoskeleton regulation.

Purpose of the Study:

  • To investigate the specific mechanism by which Clostridium difficile toxin B affects RhoA.
  • To identify the modification and its effect on RhoA function.

Main Methods:

  • Tandem electrospray mass spectrometry was used to identify and localize the modification.
  • UDP-glucose was used as a cosubstrate in vitro.
  • Microinjection of modified RhoA into cultured cells.

Main Results:

  • Toxin B catalyzes the monoglucosylation of RhoA at threonine 37.
  • UDP-glucose serves as the selective cosubstrate for this monoglucosylation.
  • Microinjected glucosylated RhoA caused actin filament disaggregation, demonstrating dominant-negative activity.

Conclusions:

  • Clostridium difficile toxin B inactivates RhoA through monoglucosylation.
  • This modification disrupts the actin cytoskeleton, contributing to the toxin's cytotoxic effects.
  • Targeting this glucosylation mechanism may offer therapeutic strategies against C. difficile infections.

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