Identifiable Helicobacter pylori strains or factors important in the development of duodenal ulcer disease.

Abstract

Helicobacter pylori is a primary pathogen as its presence in the stomach almost always is associated with a strong mucosal and systemic immune response. Putative virulence factors of H. pylori are numerous. In this article, we evaluate whether currently available evidence supports the existence of factors important in the development of duodenal ulcer disease. The evaluation is conducted by a review of the literature on H. pylori toxins and virulence factors. Most putative H. pylori virulence factors are present in all isolates examined, though some are present only in, or are expressed more intensively by, determined strains. Urease is the main virulence determinant of H. pylori. It generates ammonia from the gastric urea, which in turn injures the gastric mucosa either directly by forming ammonium hydroxide or indirectly by stimulating polymorphonuclear leukocytes and inhibiting cell proliferation. Other enzymes (e.g., mucinase, phospholipases, alcohol dehydrogenase, neuraminidase) could promote tissue erosion and ulceration by destroying the integrity of mucus, by inducing lipid peroxidation, and the like. H. pylori strains that express the vacuolating toxin vacA and the associated protein cagA are called type I and are considered to be endowed with increased ulcerogenic and inflammatory potential. Exploration of the structure of the vacA gene has shown that the degree of toxicity is regulated at the molecular level. Type I H. pylori strains carry a 40-kb genomic fragment called cag that is absent from type II strains (vacA- and cagA-negative). cag is considered a pathogenicity island because it contains numerous genes that are highly homologous to virulence genes of classic bacterial pathogens and because it has been suggested that it is acquired through recombination events. CagA is part of the pathogenicity island. CagA-positive strains are more likely to be isolated from patients with duodenal ulcer and other severe digestive pathological processes. The use of simple serological tests to identify patients infected with type I H. pylori strains could help to calculate the risk of development of severe gastroduodenal diseases and, possibly, to prevent such severe diseases.