title: Phylogeographic origin of Helicobacter pylori determines host-adaptive responses upon coculture with gastric epithelial cells.
abstract: While Helicobacter pylori infects over 50% of the world's population, the mechanisms involved in the development of gastric disease are not fully understood. Bacterial, host, and environmental factors play a role in disease outcome. To investigate the role of bacterial factors in H. pylori pathogenesis, global gene expression of six H. pylori isolates was analyzed during coculture with gastric epithelial cells. Clustering analysis of six Colombian clinical isolates from a region with low gastric cancer risk and a region with high gastric cancer risk segregated strains based on their phylogeographic origin. One hundred forty-six genes had increased expression in European strains, while 350 genes had increased expression in African strains. Differential expression was observed in genes associated with motility, pathogenicity, and other adaptations to the host environment. European strains had greater expression of the virulence factors cagA, vacA, and babB and were associated with increased gastric histologic lesions in patients. In AGS cells, European strains promoted significantly higher interleukin-8 (IL-8) expression than did African strains. African strains significantly induced apoptosis, whereas only one European strain significantly induced apoptosis. Our data suggest that gene expression profiles of clinical isolates can discriminate strains by phylogeographic origin and that these profiles are associated with changes in expression of the proinflammatory and protumorigenic cytokine IL-8 and levels of apoptosis in host epithelial cells. These findings support the hypothesis that bacterial factors determined by the phylogeographic origin of H. pylori strains may promote increased gastric disease.
authors: Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors: Alexander
authors: A
authors: Sheh
authors: Rupesh
authors: R
authors: Chaturvedi
authors: D Scott
authors: DS
authors: Merrell
authors: Pelayo
authors: P
authors: Correa
authors: Keith T
authors: KT
authors: Wilson
authors: James G
authors: JG
authors: Fox
mesh_terms: D000222:Adaptation, Physiological; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000382:microbiology* / Q000473:pathology; D005753:Gastric Mucosa / Q000166:cytology*; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D016481:Helicobacter Infections / Q000382:microbiology; D016480:Helicobacter pylori / Q000145:classification / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009068:Movement; D058974:Phylogeography; D059467:Transcriptome
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C508606:CXCL8 protein, human; D016209:Interleukin-8; C080866:cagA protein, Helicobacter pylori
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