How Does Helicobacter Pylori Bacteria Cause Stomach Cancer?

Nearly 750,000 patients die of stomach cancer every year. This stomach cancer is found to be mainly caused by Helicobacter pylori (H. pylori).

Highlights

750,000 patients die of stomach cancer each year after developing the disease. The main cause of this cancer is thought to be Helicobacter pylori (H. pylori) bacteria
Gastric cancer is one of the five most fatal types of cancer
This bacteria has been known destroy the stomach's protective layer, it secretes a protease enzyme called HtrA to penetrate these layers

Helicobacter pylori, which cause gastric cancer, secretes an enzyme, called HtrA, to penetrate stomach's protective layer found a study published in Cell Host & Microbe journal.//

Gastric cancer, also known as stomach cancer is one of the five most fatal types of cancer. According to the World Health Organization (WHO), around 750,000 patients die annually of this disease.

Stomach Cancer | Gastric Cancer
Stomach (gastric) cancer develops from the stomach lining. It is the third most common cause for cancer related deaths.

At present, there are no effective therapies for gastric cancer and growing spread of antibiotic resistance is further complicating treatment of the infection. Researchers at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) have now identified two mechanisms through which this bacterium can cause gastric cancer. Their findings could result in the development of new therapeutic approaches.

The international team of scientists headed by Dr. Nicole Tegtmeyer of the Chair of Microbiology at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) investigated how bacteria destroy the stomach's protective layer. This protective layer is composed of densely packed epithelial cells that protect the stomach against the effects of gastric acid.

The researchers have now discovered that H. pylori secrete an enzyme, a protease called HtrA, which it uses much like a weapon to penetrate this protective layer. HtrA cleaves the three proteins occludin, claudin-8, and E-cadherin, rupturing the layer of epithelial cells.

Test Your Knowledge on Gastric Cancer
Gastric cancer is also called stomach cancer as it occurs most commonly in the mucus producing cells lining the stomach. It is the seventh most common cancer among women and 5th most common cancer among men in India. A lot of research has been initiated into finding treatment measures and for reducing the risk for this type of cancer. In a study in China, it was found that cabbages and potatoes reduce the risk of gastric cancer. Studies such as these aid in controlling the incidence of this type of cancer.

As a result, the H. pylori bacteria can access deeper, normally pathogen-free tissue layers, and inflict further damage. This is the first step towards gastric cancer starting to develop.

This first phase, however, is followed by one that is even more dangerous, as the team discovered.

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Needle-like protrusions, termed type IV secretion systems, are activated and function as 'molecular syringes.' Using a receptor-dependent mechanism, these inject a bacterial toxin, the CagA protein, through the basolateral membrane of the host cells. The injected CagA subsequently reprograms host cells, making them potentially cancerous.

Another effect of this protein is that it prevents the human immune system from recognizing and eliminating the bacteria - a crucial mechanism for the long-term survival of H. pylori in the human stomach.

Stomach Cancer
Stomach cancer or gastric cancer is diagnosed late, stomach cancer infographic combines information with statistics to create awareness about the disease.

Dr. Tegtmeyer expects these findings will make it possible to develop important new antibacterial therapeutic approaches, as HtrA and CagA are ideal novel drug targets. The team has already started to test specific HtrA inhibitors. "We hope that suitable active agents can either completely prevent infection or inhibit the injection of CagA," explains Tegtmeyer.

Reference

Nicole Tegtmeyer, Silja Wessler, Vittorio Necchi, Manfred Rohde, Aileen Harrer, Tilman T. Rau, Carmen Isabell Asche, Manja Boehm, Holger Loessner, Ceu Figueiredo, Michael Naumann, Ralf Palmisano, Enrico Solcia, Vittorio Ricci, Steffen Backert11,'Correspondence information about the author Steffen Backert. Helicobacter pylori Employs a Unique Basolateral Type IV Secretion Mechanism for CagA Delivery, Cell host and microbe(2017)DOI:http://dx.doi.org/10.1016/j.chom.2017.09.005

Source-Eurekalert