ABSTRACT
Helicobacter pylori, the pathogen that infects the stomach of about half the world’s population, is associated with a spectrum of gastric diseases, ranging from gastritis to peptic ulcers and gastric cancer. Pathogenic strains of H. pylori use a type IV secretion system (T4SS) to deliver the toxin CagA into the human host cells. The T4SS, along with the toxin itself, is coded into a genomic insert, termed the cag pathogenicity island (cag-PAI). The latter contains about 30 open reading frames, most of which the exact function is not well characterized or totally unknown. In this paper, we summarize the methodology used to systematically investigate the function and structure of the proteins coded by the cag-PAI genes. Synchrotron Radiation and Structural Proteomics Edited by Eugenia Pechkova and Christian Riekel Copyright © 2012 Pan Stanford Publishing Pte. Ltd. www.panstanford.com
10.1 INTRODUCTIONEvery year, Helicobacter pylori chronically infects the gastric mucosa of millions of people worldwide: it has been estimated that over 50% of the world population carries this infection (Covacci et al., 1999), making it one of the most common. H. pylori has been associated with the development of several diseases, such as chronic gastritis, gastric and duodenal ulcer, gastric adenocarcinoma, and mucosa-associated lymphoma (Parsonnet et al., 1991; Parsonnet, 1994; Moss and Sood, 2003). Approximately 10% of individuals who are infected during childhood will develop peptic ulcer disease; more dramatically, about 1% of the infected individuals develop gastric neoplasia: this concerns over 600,000 individuals worldwide every year (Pisani et al., 1999). Many of the defined H. pylori virulence factors, including flagella, the acid neutralizing enzyme urease, the neutrophil-activating protein HP-NAP, and the vacuolating cytotoxin VacA, are found in all strains (Monack et al., 2004). Strains isolated from patients with severe diseases possess the so-called cag pathogenicity island (cag-PAI) and are defined as type I strains (Censini et al., 1996). The H.
