Infection of the stomach with H. pylori is not the cause of illness itself; most H. pylori positive cases are asymptomatic. But persistent colonisation can induce a number of gastric and extragastric disorders. Gastric disorders due to infection begin with gastritis, inflammation of the stomach.When infection is persistent the prolonged inflammation will become chronic gastritis. Initially this will be non-atrophic gastritis, but damage caused to the stomach lining can bring about the change to atrophic gastritis, and the development of ulcers both within the stomach itself or in the duodenum, the nearest part of the intestine. At this stage the risk of developing cancer is high.However, the development of a duodenal ulcer has a lower risk of cancer.Helicobacter pylori is a class I carcinogen, and potential cancers include gastric mucosa-associated lymphoid tissue (MALT) lymphomas and gastric cancer.
Study of the H. pylori genome is centered on attempts to understand pathogenesis, the ability of this organism to cause disease. About 29% of the loci have a colonization defect when mutated. Two of sequenced strains have an around 40 kb-long Cag pathogenicity island (a common gene sequence believed responsible for pathogenesis) that contains over 40 genes. This pathogenicity island is usually absent from H. pylori strains isolated from humans who are carriers of H. pylori, but remain asymptomatic.[41]
CagA (cytotoxin-associated gene A) codes for the major H. pylori virulence protein. Bacterial strains with the cagA gene are associated with the ability to cause ulcers, MALT lymphomas, and gastric cancer.[42][43] The cagA gene codes for a relatively long (1186-amino acid) protein. The cag pathogenicity island (PAI) has about 30 genes, part of which code for a complex type IV secretion system. The low GC-content of the cag PAI relative to the rest of the Helicobacter genome suggests the island was acquired by horizontal transfer from another bacterial species.[36] The serine protease HtrA also plays a major role in the pathogenesis of H. pylori. The HtrA protein enables the bacterium to transmigrate across the host cells' epithelium, and is also needed for the translocation of CagA.
Helicobacter pylori harms the stomach and duodenal linings by several mechanisms. The ammonia produced to regulate pH is toxic to epithelial cells, as are biochemicals produced by H. pylori such as proteases, vacuolating cytotoxin A (VacA) (this damages epithelial cells, disrupts tight junctions and causes apoptosis), and certain phospholipases.[58] Cytotoxin associated gene CagA can also cause inflammation and is potentially a carcinogen.
