VIRULENCE FACTORS

Motility: The structure of H. pylori is an important factor in allowing this bacteria to colonize the mucus-secreting gastric muscosa. Its spiral shape and the motion of its flagella allow it to move rapidly through the acidic environment of the stomach and into the neutral mucosal layer where it may replicate .

Urease Activity: In order to circumvent the stomach acid which does penetrate into the mucosal layer, H. pylori produces a large amount of urease (more than any species of bacteria). Urease converts urea into ammonia and bicarbonate, two strong bases which in turn neutralize the acid and provide a safe environment. The necessity of such urease activity has been proven using animal models in which urease mutants were unable to colonize and inflict any tissue damage. The break down of urea can be seen below: C=O(NH2)2 + H+ + 2H20 --urease--> HCO3 + 2(NH4+)

Adherence: In order for H. pylori to colonize the gastric mucosa, it must be able to remain attached to this tissue throughout new mucus production. It accomplishes this feat through the use of adhesins. Those H. pylori which do adhere to the mucosal layer do so in a fashion similar to Enteropathogenic E. Coli (EPEC). When the bacteria comes in close contact with the mucosal layer there results a rearrangement of the host cell actin in this area of contact. A cup-like pedestal structure forms under the bacteria, holding it in place. This phenomenon is commonly referred to as attaching and effacing. A number of possible adhesins have been identified : 1) an adhesin which binds Lewisb antigens with terminal fucose residues (blood group O antigens 2) an adhesin which binds phosphatidylethanolamine 3) an adhesin which binds sialic acid-lactose residues 4) an adhesin which agglutinates erythrocytes

Possible Virulence Factors Involved in Inducing the Inflammatory Response As seen in the image to the right, the immune system is quick to begin an attack against H. pylori. This response may be induced by LPS, Lipopolysaccharide, associated with the membrane of gram-negaive bacteria. The fragmenting of the bacterial membrane may result in the intrusion of LPS into underlying tissue, therefore sparking the immune response and inflammation. Another possible virulence factor is a cytotoxin produced by H.pylori. This toxin cause vacuole formation in mammalian cells which ultimately result in the death of the cell. These dying cells may play a role in further sparking the immune response and increasing inflammation. H. pylori produces a heat shock protein which is another possible player in virulence. This protein is capable of eliciting T-cell and antibody activity that will in turn damage host tissue. It is not yet certain how much of a role these three possible virulence factors play in infections due to H.pylori. The ability of animal models which do not contain these factors to become infected with H. pylori must be tested.