Reduced intracellular survival of Helicobacter pylori vacA mutants in comparison with their wild-types indicates the role of VacA in pathogenesis

The vacuolating cytotoxin VacA of Helicobacter pylori plays an important bu t yet unknown role in pathogenesis. We studied the impact of the vacuolatin g cytotoxin on Ii. pylori invasion of and survival within AGS cells (human gastric cell line derived from an antral adenocarcinoma). Isogenic vacA and cagA mutants were constructed in a wild-type clinical isolate H. pylori. A F4. An H. pylori VacA-deficient mutant, AF4(vacA::kan). was cultured in sig nificantly lower numbers fi om AGS cells after 24 h incubation with gentami cin added to the culture medium than were the type I wild-type strain AF4 ( P<0.03) and an isogenic cagA mutant (P<0.01). Complementation of the AF4 va cA mutant with broth culture supernatant from wild-type AF4 improved the in tracellular survival of the vacA mutant. We conclude that H. pylori's vacuo lating cytotoxin improves the intracellular survival of H. pylori within AG S cells, suggesting the role of the vacuolating cytotoxin in II. pylori pat hogenesis. (C) 2001 Federation of European Microbiological Societies. Publi shed by Elsevier Science B.V. All rights reserved.