Cytolethal distending toxin sequence and activity in the enterohepatic pathogen Helicobacter hepaticus

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V B Young1, K A Knox, D B Schauer

  • 1Division of Bioengineering and Environmental Health, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.

Infection and Immunity
|December 22, 1999
PubMed

Insights

Enterohepatic Helicobacter species cause liver and intestinal inflammation. Researchers identified the cytolethal distending toxin (CDT) genes from Helicobacter hepaticus, revealing a key factor in pathogenesis.

Area of Science:

  • Microbiology
  • Molecular Pathogenesis
  • Hepatology

Background:

  • The molecular mechanisms underlying hepatitis and enterocolitis induced by enterohepatic Helicobacter species remain largely uncharacterized.
  • Helicobacter hepaticus is a murine pathogen implicated in liver and intestinal diseases.

Purpose of the Study:

  • To investigate the molecular pathogenesis of enterohepatic Helicobacter-associated liver and intestinal inflammation.
  • To identify the genes responsible for the cytotoxic effects of Helicobacter hepaticus.

Main Methods:

  • Analysis of sonicates from Helicobacter hepaticus in HeLa cell monolayers.
  • Cloning of genes encoding cytotoxic activity from H. hepaticus.
  • Expression of cloned genes in Escherichia coli to assess cytotoxic effects.

Main Results:

  • Helicobacter hepaticus sonicates induced cell distension, actin accumulation, and G(2)/M cell cycle arrest in HeLa cells.
  • Three genes homologous to Campylobacter jejuni cdtA, cdtB, and cdtC were identified in H. hepaticus.
  • Expression of the cloned H. hepaticus cdtABC genes in E. coli replicated the observed cytotoxic activities.

Conclusions:

  • Cytolethal distending toxin (CDT) activity is a significant virulence factor for Helicobacter hepaticus.
  • CDT produced by H. hepaticus likely contributes to the pathogenesis of hepatitis and enterocolitis.
  • Understanding CDT's role provides insights into enterohepatic Helicobacter-associated diseases.

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