Cag pathogenicity island-specific responses of gastric epithelial cells to Helicobacter pylori infection.
Helicobacter pylori infects over half the world's population and causes a wide range of diseases, including gastritis, peptic ulcer, and two forms of gastric cancer. H. pylori infection elicits a variety of phenotypic responses in cultured gastric epithelial cells, including the expression of proinflammatory genes and changes in the actin cytoskeleton. Both of these responses are mediated by the type IV secretion system (TFSS) encoded by the cag pathogenicity island (cag PAI). We used human cDNA microarrays to examine the temporal transcriptional profiles of gastric AGS cells infected with H. pylori strain G27 and a panel of isogenic mutants to dissect the contributions of various genes in the cag PAI. Infection with G27 induced expression of genes involved in the innate immune response, cell shape regulation, and signal transduction. A mutant lacking the cagA gene, which encodes an effector molecule secreted by the TFSS and required for the host cell cytoskeletal response, induced the expression of fewer cytoskeletal genes. A mutant lacking cagE, which encodes a structural component of the TFSS, failed to up-regulate a superset of host genes, including the cagA-dependent genes, and many of the immune response genes. A mutant lacking the entire cag PAI failed to induce both the cagE-dependent genes and several transiently expressed cagE independent genes. Host cell transcriptional profiling of infection with isogenic strains offered a detailed molecular picture of H. pylori infection and provided insight into potential targets of individual virulence determinants such as tyrosine kinase and Rho GTPase signaling molecules.
Guillemin
Karen
K
Department of Microbiology and Immunology, Stanford University School of Medicine, CA 94305, USA. guillemin@molbio.uoregon.edu
Salama
Nina R
NR
Tompkins
Lucy S
LS
Falkow
Stanley
S
D001426:Bacterial Proteins / Q000235:genetics*; D005753:Gastric Mucosa / Q000382:microbiology*; D015967:Gene Expression Regulation, Viral; D005838:Genotype; D016481:Helicobacter Infections / Q000382:microbiology; D016480:Helicobacter pylori / Q000235:genetics* / Q000472:pathogenicity*; D006801:Humans; D016296:Mutagenesis; D020411:Oligonucleotide Array Sequence Analysis; D014158:Transcription, Genetic; D014774:Virulence / Q000235:genetics*
D001426:Bacterial Proteins; C103937:PicB protein, Helicobacter pylori