Selective increase of the permeability of polarized epithelial cell monolayers by Helicobacter pylori vacuolating toxin

J Clin Invest. 1998 Aug 15;102(4):813-20. doi: 10.1172/JCI2764.


The effects of the vacuolating toxin (VacA) released by pathogenic strains of Helicobacter pylori on several polarized epithelial monolayers were investigated. Trans-epithelial electric resistance (TER) of monolayers formed by canine kidney MDCK I, human gut T84, and murine mammary gland epH4, was lowered by acid-activated VacA. Independent of the cell type and of the starting TER value, VacA reduced it to a minimal value of 1,000-1,300 Omega x cm2. TER decrease was paralleled by a three- to fourfold increase of [14C]-mannitol (molecular weight 182.2) and a twofold increase of [14C]-sucrose (molecular weight 342.3) transmonolayer flux. On the contrary, transmembrane flux of the proinflammatory model tripeptide [14C]-N-formyl-Met-Leu-Phe (molecular weight 437.6), of [3H]-inuline (molecular weight 5,000) and of HRP (molecular weight 47,000) did not change. These data indicate that VacA increases paracellular epithelial permeability to molecules with molecular weight < 350-440. Accordingly, the epithelial permeability of Fe3+ and Ni2+ ions, essential for H. pylori survival in vivo, was also increased by VacA. High-resolution immunofluorescence and SDS-PAGE analysis failed to reveal alterations of junctional proteins ZO-1, occludin, cingulin, and E-cadherin. It is proposed that induction by VacA of a selective permeabilization of the epithelial paracellular route to low molecular weight molecules and ions may serve to supply nutrients, which favor H. pylori growth in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / pharmacology*
  • Bacterial Toxins / pharmacology*
  • Biological Transport / drug effects
  • Caco-2 Cells
  • Cadherins / isolation & purification
  • Cations / metabolism
  • Cell Polarity*
  • Dogs
  • Dose-Response Relationship, Drug
  • Epithelial Cells / drug effects*
  • HeLa Cells
  • Helicobacter pylori*
  • Horseradish Peroxidase / metabolism
  • Humans
  • Hydrogen-Ion Concentration
  • Intercellular Junctions / drug effects
  • Inulin / metabolism
  • Iron / metabolism
  • Mannitol / metabolism
  • Membrane Proteins / isolation & purification
  • N-Formylmethionine Leucyl-Phenylalanine / metabolism
  • Nickel / metabolism
  • Permeability / drug effects
  • Stomach Ulcer / etiology
  • Sucrose / metabolism


  • Bacterial Proteins
  • Bacterial Toxins
  • Cadherins
  • Cations
  • Membrane Proteins
  • VacA protein, Helicobacter pylori
  • Mannitol
  • Sucrose
  • N-Formylmethionine Leucyl-Phenylalanine
  • Nickel
  • Inulin
  • Iron
  • Horseradish Peroxidase