Regulation of Helicobacter pylori cagA expression in response to salt.
Helicobacter pylori infection and a high dietary salt intake are risk factors for the development of gastric adenocarcinoma. In this study, we tested the hypothesis that high salt concentrations might alter gene expression in H. pylori. Transcriptional profiling experiments indicated that the expression of multiple H. pylori genes, including cagA, was regulated in response to the concentrations of sodium chloride present in the bacterial culture medium. Increased expression of cagA in response to high salt conditions was confirmed by the use of transcriptional reporter strains and by immunoblotting. H. pylori CagA is translocated into gastric epithelial cells via a type IV secretion pathway, and on entry into target cells, CagA undergoes tyrosine phosphorylation and causes multiple cellular alterations. Coculture of gastric epithelial cells with H. pylori grown under high salt conditions resulted in increased tyrosine-phosphorylated CagA and increased secretion of interleukin-8 by the epithelial cells compared with coculture of the cells with H. pylori grown under low salt conditions. Up-regulation of H. pylori cagA expression in response to high salt concentrations may be a factor that contributes to the development of gastric adenocarcinoma.
Loh
John T
JT
Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Torres
Victor J
VJ
Cover
Timothy L
TL
D000942:Antigens, Bacterial / Q000096:biosynthesis* / Q000235:genetics; D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000235:genetics; D002450:Cell Communication / Q000187:drug effects; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D016480:Helicobacter pylori / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D012965:Sodium Chloride / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000382:microbiology; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016209:Interleukin-8; C080866:cagA protein, Helicobacter pylori; D012965:Sodium Chloride