ADHERENCE TO GASTRIC EPITHELIAL-CELLS INDUCES EXPRESSION OF A HELICOBACTER-PYLORI GENE, ICEA, THAT IS ASSOCIATED WITH CLINICAL OUTCOME

Most persons infected with Helicobacter pylori strains that produce va cuolating cytotoxin and possess cytotoxin-associated gene A (cagA) gen otype nonetheless remain asymptomatic, suggesting that additional gene s are important in virulence. We hypothesized that adherence to gastri c epithelium provides stimuli that induce expression of some virulence genes. Our aims were to identify expression of H. pylori genes induce d by adherence and to determine if such genes were correlated with pep tic ulceration, mucosal interleukin-8 (IL-8) levels, and gastric infla mmation. RNA was isolated from an ulcer-derived strain and a gastritis -derived strain that were exposed or not exposed to gastric epithelial cells. These RNAs were used for random arbitrarily primed reverse tra nscription polymerase chain reaction to identify newly expressed trans cripts unique to the ulcer-derived strain following adherence. Clinica l isolates of H. pylori were characterized for presence of the newly i dentified gene, and mucosal IL-8 and inflammation were examined in gas tric biopsies from the source patients. A novel H. pylori gene, iceA ( induced by contact with epithelium), was identified. DNA sequences rev ealed two families, iceA1 and iceA2. iceA1 strains were significantly associated with peptic ulceration and increased mucosal concentrations of IL-8. Both iceA1 and iceA2 were expressed in vivo by respective H. pylori strains in gastric biopsies. Adherence to gastric epithelial c ells in vitro stimulates the transcription of iceA1, an H. pylori gene that is highly correlated with pathological outcome.