Helicobacter pylori, a gram-negative, microaerophilic, motile, spiral-shaped bacterium, has been established as the etiologic agent of gastritis and peptic ulcers and is a major risk factor for gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma (MALT). The ability ofH. pylorito cause this spectrum of diseases depends on host, bacterial, and environmental factors. Bacterial factors critical forH. pyloricolonization of the gastric mucosa include urease, flagella, adhesins, and delta;-glutamyltranspeptidase. Lipopolysaccharide, urease, and vacuolating cytotoxin are among the factors that allowH. pylorito persist for decades and invoke an intense inflammatory response, leading to damaged host cells. Genes in thecagpathogenicity island also contribute to the inflammatory response by initiating a signal transduction cascade, resulting in interleukin-8 production. Proinflammatory cytokines and a Th-1 cytokine response further exacerbates the inflammation. Products of the enzymes nitric oxide synthase (iNOS) and cyclooxygenase may perturb the balance between gastric epithelial cell apoptosis (ulcer formation) and proliferation (cancer). The host Th-1 response and antibodies directed againstH. pylorido not eliminate the organism, which presents challenges to vaccine development. Vaccines that include urease have shown some promise, but improved adjuvants and animal models should hasten progress in vaccine research.H. pyloriis the most genetically diverse organism known, and the panmictic population structure may contribute to the varying ranges of disease severity produced by different strains. The complete genome sequence of two strains ofH. pylorihas propelled this field forward, and numerous groups are now using genomic, proteomic, and mutagenetic approaches to identify new virulence genes. Discovered only in 1982,H. pyloriis now among the most intensely investigated organisms. This review summarizes recent progress in this rapidly moving field.
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