Helicobacter pylori pathogenesis and disease outcomes are mediated by the complex interaction between the bacteria and virulence factors, host and environmental factors. After the H. pylori enters the stomach of the host the following four steps are very much important for the bacteria to establish the successful colonization, persistent infection, and disease pathogenesis.
The first mechanism is that the bacteria is capable of surviving in the stomach
Since the bacteria possess the flagella which helps them in the motility of the bacteria towards the surface lining the stomach.
Attachment to host cells by adhesins/receptors interaction
Causing tissue damage by toxin release.
The virulence nature possessed by the bacteria includes bacterial adhesins , cag pathogenicity and vacuolating cytotoxins. The screening methods including the proteomic and transcriptomic tools has been used to determine the complex gene regulatory networks in H.pylori.
In the acidic environment of the stomach lumen the bacteria uses the flagella to burrow into the mucus lining of the stomach to reach the epithelial cells underneath, where it is less acidic when compared to the external surface of the lumen. H. pylori is capable of sensing the pH gradient in the mucosal cells and move towards the less acidic region which is called as chemotaxis. This aids the bacteria from being swept away into the lumen with the bacteria’s mucus environment which is constantly moving from the site of creation at the epithelium to its dissolution at the lumen interface.
H. pylori is found in the mucus, on the inner surface of the epithelium. The bacteria produces adhesins which helps the bacteria to bind to the lipids and carbohydrates of the epithelial cell membrane. The adhesin which is termed as the BabA binds to the Lewis b antigen displayed on the surface of the stomach epithelial cells. H. pylori adherence via BabA is acid sensitive and it can be reversed by decreased pH. This adhesin BabA’s acid response enables adherence and also helps the bacteria to escape from the acidic environment present in the stomach and favours the growth of the bacteria to adapt itself in this environment. Another such adhesin, SabA binds to increased levels of sialyl – Lewis x antigen expressed on gastric mucosa. In addition to using chemotaxis to restrict the areas of low pH, H.pylori also neutralizes the acid in the environment by producing the large amounts of the urease which breaksdown the urea present in the stomach to carbon di oxide and ammonia. These reaction with the strong acids in the environment produces a neutralized area around H. pylori. Urease mutants are incapable of colonization. The urease expression is not only required for the initial colonization but it is also required for the sustaining the chronic infection.
This urease enzyme produced by the bacteria leads to the formation of the ammonia and helps the bacteria to survive in the acidic environment. Arginase secreated by the bacterium in human stomach a member of the ureohydrolase family, catalyzes the conversion of L – arginine to L – ornithine and urea where thr ornithine is converted into polyamines which plays a major role in various metabolic process.
The above mechanism elicited by the bacteria provides the acid resistance and it is the important for colonization of the bacterium in the gastric epithelial cells. This reduces the synthesis of NO which plays an important role in the innate immunity and an effective antimicrobial agent that is able to kill the invading the pathogens. The changes in the availability of L arginine and its metabolism into polyamines results in deteriorated activity of the host innate immune mechanism