Expression and activity of the cytolethal distending toxin of Helicobacter hepaticus

Biochem Biophys Res Commun. 2004 Jun 4;318(3):739-45. doi: 10.1016/j.bbrc.2004.04.089.

Abstract

Helicobacter hepaticus, a causal agent of hepatocarcinoma in mice, exhibits a cytolethal distending toxin activity. The three subunits of this holotoxin, CdtA, CdtB, and CdtC, and three CdtB mutants were produced as recombinant histidine-tagged proteins by using an in vitro cell-free protein expression system. We found that the presence of the three H. hepaticus Cdt subunits is required for cellular toxicity and that only a C-terminal CdtB mutation abolishes the activity of the complex. In vitro, H. hepaticus CdtB exhibits a DNase activity which is also abolished by this C-terminal CdtB mutation. These results suggest that the effect of H. hepaticus CDT probably involves the DNase activity of CdtB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Animals
  • Bacterial Toxins / biosynthesis*
  • Bacterial Toxins / chemistry
  • Bacterial Toxins / genetics
  • Bacterial Toxins / toxicity*
  • Cell Survival / drug effects
  • Cells, Cultured
  • Deoxyribonucleases / metabolism
  • Gene Expression
  • Helicobacter hepaticus / genetics
  • Helicobacter hepaticus / metabolism*
  • Liver / cytology
  • Mice
  • Mice, Inbred C3H
  • Molecular Sequence Data
  • Protein Biosynthesis
  • Protein Structure, Tertiary
  • Protein Subunits
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / toxicity
  • Sequence Alignment

Substances

  • Bacterial Toxins
  • Protein Subunits
  • Recombinant Proteins
  • cytolethal distending toxin
  • Deoxyribonucleases