PROBLEMS

Helicobacter pylori

Helicobacter pylori is a helical shaped, Gram-negative, microaerophilic bacterium found in several areas in the stomach with the property of inflammation of these areas of the stomach. This bacteria can cause chronic or acute inflammation in the stomach wall. Moreover it is the most common cause for gastric ulcer and cancer development in the world.

Helicobacter pylori was identified in 1982 by Dr. Barry Marshall and Dr. Robin Warren, who found that it was present in patients with chronic gastritis and gastric ulcers. In 2005 these scientists made this discovery, awarded with the Nobel Prize in Physiology or Medicine.

H. pylori is about 3 micrometer long with a diameter of about 0.5 micrometer. H. pylori is microaerophilic, means that it requires oxygen, but at lower concentration than it is found in the atmosphere. With this attribute it can easily survive and grow in the gastrointestinal tract. H. pylori has got lots of flagella on the cell membrane, which starts from only one point. Thanks to these flagella Helicobacter types can easily and quickly move in the gastrointestinal system. H. pylori produces several enzymes like urease, catalase and oxidase. The enzyme urease enables the survival of the bacteria at low pH levels like the gastric juice (pH: 2.0) for a specific time period.

More than %50 of the world's population harbor H. pylori in their gastrointestinal tract and this statistic make the H. pylori to the most common infection. When we take a global look on developing countries the prevalence is 90% compared with the prevalence of industrialized countries of 40%.

H. pylori in the gastrointestinal system especially causes the stomach inflammation. Although it is able to survive in the gastric juice by help of the urease enzyme, it cannot survive at low pH for a long time. For this reason it moves away from the gastric juice and enters to the stomach mucus layer, that has got a more basic pH. Because of the gel structure of the stomach mucus layer, it has got a higher density than normal liquid. Only H. pylori can move easily in this dense area through its several flagella. H. pylori found in the mucus layer adhered to the stomach wall, grows up here and settles near to the stomach mucosa cells. At the same time it starts to secrete different factors that harm these cells. Consequently the located tissue gets injured and different sized big wounds occurs.

Nowadays, when H. pylori is detected in a person, the 'triple therapy' is administered. This therapy method consists of two antibiotics (amoxicillin and clarithromycin) that inhibit the growth of the bacteria and proton pumps, eventually cure the injuries. However, because of several reasons a sufficient success couldn't be reached. The biggest reason for this failure in this triple therapy is the developed resistance against the used antibiotics. Although 30 years have passed since the relations between ulcer and cancer have been found, a therapy method that aims the eradication of H. pylori couldn’t be achieved. For this reason, more research for a new therapy will be needed for long term success H. pylori eradication.

Patients, who infected with H. pylori show off two main diseases. These are gastric ulcer and gastric cancer.

Gastric Ulcer

The H.pylori is located in the mucus layer of the stomach and close to stomach mucosa cells, secretes several factors. These factors lead to injury or death of the cells in the near area. As a result, different sized wounds called 'ulcer', occur in outmost layer of stomach, mucosa. These wounds, that have the characteristics to grow and spread over time, prevent to healthy working of the gastrointestinal system and decrease the life quality of the patient. Next to the environmental and hereditary causes, the biggest reason of ulcer is an infection with the H.pylori.

Currently 4 million people suffer from ulcer in the USA and each year 300.000 people diagnosed with ulcer. Each year 300 person die with the cause of this disease.

Gastric Cancer

The H.pylori located in the mucus layer of the stomach, produces and secretes factors with the carcinogenic effect on the stomach mucosa cells. These secreted factors cause the gastric cancer which means the loss of the cell cycle control and to grow of the cells irregular and extremely. In the next phase of the occurred cancer, cells have the possibility of spreading through blood and lymph ways and by this way an even more serious disease condition arises.

Gastric cancer is the fourth most common cancer in the world. Taking a look on all cancer types, cancer dependent deaths take place as third in women and second as in men. Each year 990.000 people are diagnosed with cancer and each year 738.000 people die because of this disease. Also in the USA each year 17.000 people are newly diagnosed and 24.000 people die with the cause of this disease.

Our Strategy

During the therapy of the two main diseases ulcer and gastric cancer caused by H.pylori, firstly the eradication of the cause has to be aimed. For this reason, first of all we aimed to eradicate H.pylori from the stomach. Due to the inefficiency of the antibiotics, we decided to use our modified E.coli. When we take a general look on our project, our bacteria will survive by imitating the H.pylori(1), and will reach the area H. pylori lives(2). After that with a gate system our bacteria will detect the existence of the H.pylori(3) and with the antimicrobial peptide Pexiganan, that is discovered recently and proofed with efficiency, the eradicaton of H.pylori is will be achieved(4). If the H.pylori is eradicated completely from the stomach, the ulcerated areas of the stomach already have the capacity to heal by the natural systems of the body. However we cannot say the same thing for gastric cancer. Even when the H.pylori is eradicated, if a gastric cancer had developed, there will not be a natural healing. In our project we aim the eradication of H.pylori and the left cancer cells at the same time. For cancer we want to achieve this with an intracellular-miRNA-amount-dependent-switch-system. We designed this system for the eradication of cancer cells without injuring the healthy cells.

As a result, the main cause of the two diseases H. pylori will be exterminated and at the same time cancerous areas will be cured.