Pathogenesis of Helicobacter pylori infection

Helicobacter pylori, a gram-negative, microaerophilic, motile, spiral-shape d bacterium, has been established as the etiologic agent of gastritis and p eptic ulcers and is a major risk factor for gastric adenocarcinoma and muco sa-associated lymphoid tissue lymphoma (MALT). The ability of H. pylori to cause this spectrum of diseases depends on host, bacterial, and environment al factors. Bacterial factors critical for H. pylori colonization of the ga stric mucosa include urease, flagella, adhesins, and delta-glutamyltranspep tidase. Lipopolysaccharide, urease, and vacuolating cytotoxin are among the factors that allow H. pylori to persist for decades and invoke an intense inflammatory response, leading to damaged host cells. Genes in the cag path ogenicity island also contribute to the inflammatory response by initiating a signal transduction cascade, resulting in interleukin-8 production. Proi nflammatory cytokines and a Th-1 cytokine response further exacerbates the inflammation. Products of the enzymes nitric oxide synthase (iNOS) and cycl ooxygenase may perturb the balance between gastric epithelial cell apoptosi s (ulcer formation) and proliferation (cancer), The host Th-1 response and antibodies directed against H. pylori do not eliminate the organism, which presents challenges to vaccine development. Vaccines that include urease ha ve shown some promise, but improved adjuvants and animal models should hast en progress in vaccine research. H. pylori is the most genetically diverse organism known, and the panmictic population structure may contribute to th e varying ranges of disease severity produced by different strains. The com plete genome sequence of two strains of H. pylori has propelled this field forward, and numerous groups are now using genomic, proteomic, and mutagene tic approaches to identify new virulence genes. Discovered only in 1982, H. pylori is now among the most intensely investigated organisms. This review summarizes recent progress in this rapidly moving field. (C) 2000 Lippinco tt Williams & Wilkins, Inc.