Stomach disease triggered by molecular switch! - ANI News

Washington D.C. [USA], Jan 11 (ANI): The helicobacter pylori (H Pylori) bacteria, which is found in the stomachs of nearly half of the world's population, is known to be a major cause for ulcers, MALT lymphoma and adenocarcinoma.
A new mechanism that controls the causes of infection due to H Pylori that triggers the development of stomach diseases has been revealed by researchers in an FAU study.
It is hoped that these findings will lead in time to new therapies. The study was published in the journal Nature Communications.
A team of national and international scientists led by Prof Dr Steffen Backert from the Chair of Microbiology at FAU has investigated how the bacteria manipulate the host's immune system in order to ensure their long-term survival in the stomach. Chronic inflammation is the most common cause of stomach illnesses such as these.
The researchers have identified a 'molecular switch' which uses a previously unknown mechanism to regulate the inflammation reaction in the stomach. The interaction between H Pylori and stomach cells activates a syringe-like pilus structure referred to as a type IV secretion system.
A protein, CagL, is presented at the surface of this structure which allows the bacterial toxin known as CagA protein to be delivered into the stomach cells.
The injected CagA then re-programs the host cell so that stomach cancer can develop. It now appears that CagL also has another important function, however. The protein is recognized by the immune system via the receptor TLR5. Experiments in mouse models have demonstrated that TLR5 controls the infection efficiently. CagL imitates a TLR5 recognition motif in the flagellin protein of other pathogens, thereby controlling the human immune response.
Interestingly, this signaling pathway can be both switched on and switched off by the type IV secretion system, which is not thought to be the case with other bacteria. Presumably, H Pylori has exploited this signaling pathway over thousands of years of evolution to eliminate 'bothersome' bacterial competitors in the stomach.
At the same time, CagL influences the congenital and adaptive immune system as well as the inflammation reaction in such a way that H Pylori itself is not recognised and therefore cannot be eliminated, a mechanism which is crucial for long-term infections with H Pylori in the stomach and triggering stomach disease.
Researchers also observed that TLR5 is no longer produced in healthy stomach cells and once an infection has been resolved. This indicates that the expression of this protein is a new indicator of stomach disease in humans triggered by H Pylori.
Prof Backert hopes that these findings will help develop significant new approaches for anti-bacterial treatment, as CagL, CagA and TLR5 lend themselves well to treatment. The participating researchers have already started to test appropriate substances.
"We hope that specific inhibitors can paralyse the function of the type IV secretion system, or partially or entirely prevent infection," says Prof Backert. (ANI)

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