Diversity of Helicobacter pylori vacA gene and cytotoxin production

Objective: To determine the frequency of different alleles of the vacA gene among the strains of Helicobacter pylori isolated from children and adults, and to compare vacuolating cytotoxin production with different combinations of vacA alleles.
Methods: H. pylori strains were isolated from the gastric biopsy samples of 100 patients with duodenal ulcer (32) and chronic gastritis (68). Bacterial DNA was extracted and the vacA alleles typed using PCR. Cytotoxin activity was assessed by an Intestine 407 cell vacuolation assay.
Results: Alleles s1 and s2 of vacA were identified in 72% and 28% of the tested strains, respectively. Of the 72 type s1 strains, 71 were classified as type s1a and only one as s1b. The predominant sequence observed in the vacA middle region was the m2 type (65%). Combinations of vacA genotypes s1a m1, s1a m2 and s2 m2 were found in 35%, 36% and 28% of strains, respectively. Vacuolating cytotoxin was produced by vacA s1a m1 strains isolated from patients with duodenal ulcer (84.6%) and chronic gastritis (68.2%). Subtype s1a m2 strains expressed vacuolating cytotoxin less frequently in both duodenal ulcer (47.1%) and chronic gastritis (21.1%) patients (   p <0.01  ). Antibodies to VacA (89 kDa) were found in 71.9% of patients with duodenal ulcer and in 42.6% of patients with chronic gastritis.
Conclusions: Most H. pylori vacA s1 m1 strains are toxic, whereas s2 m2 forms are essentially non-toxic.