Helicobacter pylori virulence factors: facts and fantasies

Virulence factors are related to the ability of a microbe to induce disease. True virulence factors must therefore have a disease association, an in-vivo correlate with disease such as increased mucosal inflammation, or both.

The cytotoxin-associated gene pathogenicity island; the outer membrane inflammatory protein; the duodenal ulcer-promoting gene, and possibly the blood group antigen-binding adhesion, are the only factors that to date qualify as virulence factors. Numerous recent studies have investigated the interaction of vacuolating cytotoxin A or cytotoxin-associated gene A with cells and cell lines in vitro. It remains unclear, however, whether any of the findings, for example, in-vitro experiments showing that vacuolating cytotoxin A affect the regulation of T or B lymphocytes, have an in-vivo counterpart, or play any role in disease pathogenesis.

The criteria for a virulence factor include evidence of an association with a disease or a disease surrogate such as the severity of mucosal inflammation, epidemiologic consistency, and biologic plausibility. Confirmation of the proposed mechanism requires elimination of the effect by gene deletion and restoration by complementation. Cytotoxin-associated gene A has been the subject of elegant biochemistry despite lack of evidence that it is involved in pathogenesis. The current focus of research on Helicobacter pylori relates to exploring the biology of Helicobacter pylori, often using systems that only vaguely relate to the in-vivo conditions or to disease pathogenesis.