Toxins of the Helicobacter Genus and Their Roles in Pathogenesis

Abstract

In the 20 years since the discovery of Helicobacter pylori the number of formally described Helicobacter spp. has increased dramatically. The majority of species in the genus have been associated with some form of pathology. Similar to other Gram-negative bacteria, all helicobacters have lipopolysaccharides or endotoxins in the outer leaflet of their outer membrane which is an important modulator of the immune system. H. pylori endotoxin has a number of roles in the pathogenesis of the bacterium. Its relatively low biological and immunological activity and molecular mimicry may contribute to the chronic nature of infection through avoidance of host defence mechanisms and adhesion. In addition to endotoxins, various helicobacters also secrete distinct exotoxins capable of host cell damage. H. pylori has been shown to possess a cytotoxin capable of inducing vacuoles in epithelial cells termed vacuolating cytotoxin or VacA. Although VacA has a number of roles in the pathogenesis of H. pylori its use as a predictor of clinical outcome has yet to be established. In addition, similar to the closely related Campylobacter jejuni, a number of enterohepatic helicobacters express a cytolethal distending toxin capable of inducing severe cell damage in vivo and in vitro. Both endotoxins and exotoxins may play a combined role in the pathogenesis of Helicobacter spp. Both toxin types have been identified as being present on outer membrane vesicles shed by H. pylori which may act as antigen delivery vehicles and contribute to pathogenesis.