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( Jane Oh ),( David Scott ),( Elizabeth Marcus ),( Yi Wen ),( George Sachs ) 대한소화기학회 2007 SIDDS Vol.9 No.-
Background/Aims: Helicobacter pylori is a gastric-dwelling pathogen responsible, with acid secretion, for peptic ulcer and a 20-fold increase in the risk of gastric cancer. Several transcriptomes have been described after short-term exposure to acidity in vitro, but there are no data identifying the effects of chronic gastric exposure on bacterial gene expression. Comparison of the in vivo to the in vitro transcriptome at pH 7.4 identified several groups of genes of Known function that increased expression >2-fold, and three of these respond both to acidity in vitro and to gastric infection. Methods: Mongolian gerbils were inoculated by gavage with H. pylori strain 69a expressing green fluorescent protein (GFP-Hp). Ten days after inoculation, the animals were killed, and their stomachs were rapidly removed, H. pylori RNA from the fundic and antral mucosae was isolated and enriehed by using MICROBEnrich and MICROBExpress BacterialmRNAenrichment kits (Ambion, Austin, TX). cDNA was synthesized by reverse transcription from in vivo H. pylori RNA in the presence of Cy5-dCTP and from in vitro cultured H. pylori RNA with Cy3-dCTP and hybridized to glass slides containing the 1,534 predicted ORFs of H. pylori strain 26695 (5). Microarray analysis was performed by using Phoretix Array software (Nonlinear Dynamic, Durham, NC). Results: Almost all known acid acclimation genes are highly up-regulated. There is also up-regulation of two groups of motility and chemotaxis genes and for pathogenicity island genes, especially cagA, a predictor for pathogenicity. Most of these genes interact with HP0166, the response element of the pH-sensing two-component histidine kinase. Conclusions: Based on the pH profile of survival of urel deletion mutants in vitro and their inability to survive in gastric acidity, the habitat of the organism at the gastric surface is acidic with a pH<4.0. Hence, the pH of the habitat of H. pylori on the surface of the stomach largely determines the regulation of these specific groups of genes.