Helicobacter pylori
About 2/3 of the world population are infected by the bacterium. Under poor sanitary conditions, one commonly finds infected children; in the U.S, older people (about 50% of those over the age of 60, 20% of those under the age of 40), and poor people are more likely to be infected. The infection apparently persists for life; the immune system cannot fend off the organism. The bacteria have been isolated from feces, saliva and dental plaque of infected patients, which suggests possible transmission routes. One can test for H. pylori infection with blood antibody tests, breath tests (where the patient drinks 14C or 13C labeled urea, which the bacterium metabolizes to carbon dioxide that can be detected in the breath), or endoscopy.
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Genome studies
Several strains are known, and the genomes of two have been completely sequenced. The Pylori Gene website allows easy access to genome information for the H. pylori 26695 and H. pylori J99 strains. There are 62 genes in the "pathogenesis" category of this database. Both of these sequenced strains have an approximately 40 kb long Cag pathogenicity island 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.
Study of the H. pylori genome is centered on attempts to understand the ability of this organism to cause disease. The cagA gene codes for one of the major H. pylori virulence proteins. Bacterial strains that have the cagA gene are associated with an ability to cause severe ulcers. The cagA gene codes for a relatively long (1186 amino acid) protein. The CagA protein is transported into human cells where it may disrupt the normal functioning of the cytoskeleton. The Cag pathogenicity island has about 30 genes that code for a complex type IV secretion system. After attachment of H.pylori to stomach epithelial cells the CagA protein is injected into the epithelial cells by type IV secretion system. The CagA protein is phosphorylated on tyrosine residues by a host cell membrane-associated tyrosine kinase. Pathogenic strains of H. pylori have been shown to activate the epidermal growth factor receptor (EGFR), a membrane protein with a tyrosine kinase domain. Activation of the EGFR by H. pylori is associated with altered signal transduction and gene expression in host epithelial cells that may contribute to pathogenesis. It has also been suggested that a c-terminal region of the CagA protein (amino acids 873-1002) can regulate host cell gene transcription independent of protein tyrosine phosphorylation.
Additional physiology
Gastric cancer (rare) has been associated with H. pylori. Two related mechanisms by which H. pylori can promote cancer are under investigation. One mechanism involves the enhanced production of free radicals near H. pylori and an increased rate of host cell mutation. The other proposed mechanism has been called a "perigenetic pathway" [1] and involves enhancement of the transformed host cell phenotype by means of alterations in cell proteins such as adhesion proteins. It has been proposed that H. pylori induces in inflammation and locally high levels of TNF-alpha. According to the proposed perigenetic mechanism, inflammation-associated signaling molecules such as TNF-alpha can alter gastric epithelial cell adhesion and lead to the dispersion and migration of mutated epithelial cells without the need for additional mutations in tumor suppressor genes such as genes that code for cell adhesion proteins.
History
The bacterium and its link to peptic ulcers was described first in 1982 by two Australian researchers: Robin Warren and Barry Marshall. Before the discovery, stress or diet were considered the primary causes of these ulcers. They were treated with drugs that neutralize stomach acid or decrease its production. While this worked well, the ulcers very often reappeared. Acceptance in the medical community of the role of H. pylori was slow. In 1994, the NIH conducted a conference which ended with a consensus statement affirming the causative role of H. pylori in these diseases.
The bacterium was initially called Campylobacter pyloridis, then C. pylori and finally placed in its own genus Helicobacter. Some other species of that genus have now been identified in the stomachs of other mammals and some birds.
Eradication therapy
In gastric ulcer patients where H. pylori is present, the fist-line therapy is the eradication of the organism causing the ulcer. The standard first-line therapy is a one week triple-therapy of amoxicillin, clarithromycin and omeprazole - though sometimes a different proton pump inhibitor is substituted, or metronidazole is used in place of amoxicillin in those hypersensitive to penicillin. Such a therapy has revolutionised the treatment of gastric ulcers and has made a cure to the disease possible, where previously symptom-control using antacids or H2-antagonists was the only option.