Characteristics of the organism and its antigens

Helicobacter pylori is a gram-negative, S-shaped, motile, microaerophilic bacterium which is characterized by the production of significant quantities of urease and the presence of multiple (5-7), unipolar, sheathed flagella with terminal bulbs. H. pylori primarily colonizes the gastric epithelium of humans and some nonhuman primates. Infection is probably acquired in childhood and colonization, once established, is probably lifelong. This infection is almost always associated with histologic chronic (type B) gastritis and is a major risk factor for the develop ment of peptic ulceration, atrophic gastritis, gastric-cancer and gastric lymphoma.

H. pylori isolates are biochemically and anti-genically surprisingly homogeneous despite significant genomic variation. Recently the entire genome of one H. pylori strain has been sequenced. A number of antigens of H. pylori have now been identified, including the urease which is a 540 kDa multimeric, immunodominant protein comprising six subunits of two polypeptides (28 kDa and 61 kDa) encoded by the ureA and ureB genes respectively. Monoclonal antibodies directed against the 28 kDa polypeptide can inhibit the enzyme's activity. This urease is anti-genically highly conserved among a wide variety other spiral gastric colonizing organisms, indicating that the enzyme has evolved with an essential role in gastric epithelial colonization. A third polypeptide (54 kDa), frequently associated with the urease, is an hsp60 homolog (GroEL-like) encoded by the HspB gene.

The flagella of H. pylori comprise two immunogenic flagellins (about 54 and 56 kDa) encoded by the flaA and flaB genes. The flagella sheath material is antigenic and at least some of its antigens are distinct from the outer membrane of the bacterium. Fla-gella-associated proteins are antigenically cross-reactive with the flagellins of the Campylobacters.

About 60% of H. pylori strains express an 87 kDa antigen which is the polypeptide subunit of the 970 kDa multimeric VacA protein possessing vacuolating cytotoxic activity. The subunits are encoded by the vacA gene which is also present in nontoxigenic strains. There is also a cytotoxin-associated protein (120-140 kDa) expressed from the cagA gene and present in about 80% of strains. The CagA protein is not required for toxin activity but may have a role in its regulation. Both the CagA and VacA proteins are highly antigenic.

H. pylori produces a variety of hemagglutinins, including the N-acetylneuraminyl-lactose-binding fibrillar-like hemagglutinin encoded by the HpaA gene, but their role in specific adherence to gastric epithelial cells is still debatable.

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