Helicobacter pylori VacA cytotoxin associated with the bacteria increases epithelial permeability independently of its vacuolating activity

Polarized epithelial monolayers of Madin-Darby canine kidney (MDCK) cells w ere used to study the pathogenicity of Helicobacter pylori, with an emphasi s on the effect of VacA. The adherence of H. pylori to MDCK monolayers resu lted in a decrease in trans-epithelial resistance (TER) across the cell mon olayer. Isogenic vacA mutants did not lower the TER, demonstrating that the effect is strictly linked to the action of the toxin. A similar effect was observed with all VacA-producing strains, including those producing m2 tox ins that are inactive in the vacuolating assay. In contrast to that seen wi th purified toxin, TER decrease was not enhanced by acid ph, which may indi cate that the toxin associated to the bacterial surface is possibly in a mo nomeric state and therefore does not require a ph-induced conformation to b e active. These data raise the possibility that one role of VacA in ulcerog enesis may consist of increasing the paracellular permeability of the gastr ic epithelium.