Enterotoxic effect of the vacuolating toxin produced by Helicobacter pylori in Caco-2 cells

J Infect Dis. 1998 Nov;178(5):1373-8. doi: 10.1086/314427.


Preliminary clinical evidence suggests that Helicobacter pylori may be associated with diarrhea through its vacuolating toxin (VacA). To establish whether VacA induces intestinal secretion, epithelial damage, or both, purified pH-activated VacA was added to Caco-2 cell monolayers mounted in Ussing chambers, and electrical parameters were monitored. Mucosal addition of VacA induced an increase in short circuit current, consistent with enterotoxic effect. The effect was time- and dose-dependent and saturable. It was not found if the toxin was not pH-activated, added to the serosal side, or preheated. In cells preloaded with the Ca2+ buffering compound BAPTA/AM or with the Cl- channel inhibitor 5-nitro-2-3-(3-phenylpropylamino)benzoic acid, short circuit current did not change, indicating that VacA induces activation of Ca2+-dependent Cl- channels. VacA did not show cytopathic effects, as judged by tissue resistance. These results support the hypothesis that H. pylori may be associated with diarrhea through production of VacA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / administration & dosage
  • Bacterial Proteins / biosynthesis
  • Bacterial Proteins / toxicity*
  • Bacterial Toxins / administration & dosage
  • Bacterial Toxins / biosynthesis
  • Bacterial Toxins / toxicity*
  • Biological Transport / drug effects
  • Caco-2 Cells / drug effects
  • Cytotoxins / administration & dosage
  • Cytotoxins / biosynthesis
  • Cytotoxins / toxicity*
  • Dose-Response Relationship, Drug
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Electric Impedance
  • Helicobacter pylori / metabolism*
  • Humans
  • Indicators and Reagents / pharmacology
  • Intestines / drug effects*
  • Vacuoles / drug effects


  • Bacterial Proteins
  • Bacterial Toxins
  • Cytotoxins
  • Indicators and Reagents
  • VacA protein, Helicobacter pylori
  • Egtazic Acid
  • 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid