Gene structure of the Helicobacter pylori cytotoxin and evidence of its key role in gastric disease

doi:10.1084/jem.179.5.1653

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Gene structure of the Helicobacter pylori cytotoxin and evidence of its key role in gastric disease

JL Telford, P Ghiara, M Dell'Orco, M Comanducci, D Burroni, M Bugnoli, MF Tecce, S Censini, A Covacci and Z Xiang
Department of Molecular Biology, Immunobiological Research Institute Siena, Italy.

The gram negative, microaerophilic bacterium Helicobacter pylori colonizes the human gastric mucosa and establishes a chronic infection that is tightly associated with atrophic gastritis, peptic ulcer, and gastric carcinoma. Cloning of the H. pylori cytotoxin gene shows that the protein is synthesized as a 140-kD precursor that is processed to a 94-kD fully active toxin. Oral administration to mice of the purified 94-kD protein caused ulceration and gastric lesions that bear some similarities to the pathology observed in humans. The cloning of the cytotoxin gene and the development of a mouse model of human gastric disease will provide the basis for the understanding of H. pylori pathogenesis and the development of therapeutics and vaccines.
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