Virulence factors | Helicobacter pylori

Virulence factors

Furthermore, Helicobacter pylori produces urease, an enzyme that breaks down urea into ammonia and CO2. This raises the pH in the bacterium’s surrounding medium, i.e. it is converted into a less acidic environment. The neutral environment is called the ammonia mantle.

Helicobacter pylori also produces virulence factors such as the vacuolating VacA and cagA. The toxin VacA has a variety of tasks.Among other things, it forms vacuoles in gastric epithelial cells, induces the suicide of cells (apoptosis) and inhibits special defence cells of the immune system (T-lymphocytes). Presumably, it also plays a role in the development of secondary diseases, which is not yet understood.

VacA is produced by about 50% of the Helicobacter pylori strains. The protein cagA can be introduced from the bacterium into the epithelial cells of the stomach. There it binds to structures and alters signaling pathways that have cell growth and migration properties.

According to the results of several studies, cagA could induce secondary diseases and even be directly involved in tumor development. There are invasive and non-invasive diagnostic methods to detect Helicobacter pylori. In the invasive methods, the upper gastrointestinal tract (gastrointestinal tract) is examined with a special imaging procedure using a camera (endoscopy).

The tissue samples (biopsies) taken from the stomach mucosa are examined in different ways. The enzymatic rapid test makes use of the already mentioned enzyme reaction by urease. This test is called Helicobacter urease test (HUT).

In addition, bacteria are searched for under the microscope, a bacterial culture is prepared and Helicobacter pylori is tested using molecular genetic methods such as the polymerase chain reaction, which can multiply the genetic material of the bacterium. With the help of the culture or the HUT living pathogens can be detected. The non-invasive diagnostic methods do not require the removal of tissue by endoscopy, but are nevertheless suitable for detecting Helicobacter pylori in the stomach.

The CO2 produced in the urease reaction can be detected in the air by means of a breath test (urea breath test). A special test can examine the patient’s stool for Helicobacter pylori components that are recognized by the organism as foreign and are fought by the immune system (antigens). Some other test methods detect antibodies against Helicobacter pylori in the patient’s blood, urine or saliva, but cannot provide a stand-alone statement about the current infection status, but only in connection with the patient’s medical history (= anamnesis).

The Helicobacter pylori -urease rapid test within the scope of an endoscopy is nowadays part of the routine examination in case of suspected Helicobacter pylori infection with a conspicuous endoscopic finding. In control examinations after therapy, as well as in patients with unclear upper abdominal complaints without additional symptoms, a urease test is performed if endoscopy is not performed. In epidemiological studies, antigen-antibody reactions in the blood (serology) are more likely to be tested.

The detection methods therefore differ with regard to different patient histories with pre-existing chronic Helicobacter pylori infection or suspected initial infection and with regard to therapeutic intervention. These articles may also be of interest to you:

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Reinfections are rather rare and occur after successful treatment in about 1% of those affected. Without treatment, the infection will last a lifetime.

This is generally not a problem as long as there is no inflammation of the gastric mucosa or other risk factors that can be made responsible for additional damage to the gastric mucosa. A purely prophylactic (=preventive) therapy is no longer recommended nowadays, contrary to the previously common practice. It is only recommended in medical guidelines in the event of an after-effect, known family members with a stomach tumor, after removal of parts of the stomach, in the case of a healed stomach tumor or in the case of long-term therapy with non-steroidal painkillers such as ibuprofen or diclofenac as well as glucocorticoids, the cortisol.

The process of removing the germ is called eradication. The typical therapy consists of a combination of usually 2 different antibiotics and an additional proton pump inhibitor. This therapy then takes about 7-10 days.

Depending on which scheme the doctor chooses, one speaks then of the Italian or French triple therapy, since three drugs are used for treatment. These mentioned schemes are only the most frequently used combination possibilities, there are however many more, which are then used in individual cases.Since the bacterium can no longer be killed by many of the usual antibiotics, it is often necessary to try several combinations of antibiotics and the therapy can last up to 8 weeks. The therapy is only considered to be successful if no bacteria can be detected in a new gastroscopy after several weeks.

Proton pump inhibitors Proton pump inhibitors are always part of the therapy in the treatment of Helicobacter pylori. Proton pump inhibitors block a special structure in the gastric mucosa cell, the so-called proton pump, which is responsible for the production of gastric acid, i.e. hydrochloric acid. In this way, the balance of aggressive acid and protective gastric juices, which was shifted by excessive stomach acid production, is restored and the stomach can recover from the damage and inflammation.

Very common are side effects in the gastrointestinal tract, as the digestion of food is altered by the fact that the beginning of digestion in the stomach cannot take place as usual. This can have various effects ranging from constipation to diarrhea, nausea and vomiting and flatulence. Metabolism in the liver can change the liver values, which are determined as standard during blood sampling.

This usually results in increased liver values. However, these values will in most cases decrease again after the end of the therapy and only in extremely rare cases an inflammation of the liver (=hepatitis) can occur. Occasionally, symptoms such as dizziness, headaches, tiredness or sleep disturbances may still occur.

However, these symptoms usually improve in the course of therapy and should not lead to an immediate discontinuation of taking the medication. Permanent intake is currently being discussed with a higher risk of osteoporosis, in which an increased rate of hip or vertebral body fractures is suspected. Visual and hearing disorders are extremely rare and usually only occur after treatment directly into the blood vessels, i.e. not as a tablet, as part of hospital treatment.

If affected persons notice these side effects per se, they should inform the treating physician. AntibioticsAmong the antibiotics there are different types and substances used in the treatment of Helicobacter pylori. The different combinations are nowadays struggling with many resistances of the germ, so that often several combinations have to be tried until the therapy is successful.

The antibiotic clarithromycin is used very often. Clarithromycin is part of a group of antibiotics called macrolides. These hinder the production of proteins in a bacterium, which are essential for the life of the bacterium.

Many people are probably familiar with it from the treatment of infections of the respiratory tract, such as bronchitis, pneumonia, or from the treatment of middle ear infections (= Otitis media), tonsillitis or sinusitis. Side effects may include nausea, vomiting, diarrhea, dizziness, insomnia or hypersensitivity reactions and should be read in the package insert. Also often used is the antibiotic amoxicillin, which belongs to the group of aminopenicillins.

This group is very closely related to the classic penicillins and inhibits the development of the outer shell of bacteria. In addition to its use in Helicobacter pylori infections, it is also used for infections of the digestive tract, biliary tract, urinary tract or, like Clarithromycin, for various infections of the head and neck and respiratory tract. Patients with a penicillin allergy should also refrain from amoxicillin therapy if possible.

However, side effects can always occur, as with any medication, and usually include gastrointestinal disorders such as nausea, vomiting or diarrhea. If side effects occur, a physician should be consulted to jointly consider whether a change of antibiotics is advisable. The last antibiotic most commonly used in the treatment of Helicobacter pylori infection is metronidazole, a radical generator.

These form small aggressive molecules, the radicals, which damage the bacterium’s genetic material, the DNA, and cause the bacterium to die. Human genetic material cannot be damaged by the radicals. The antibiotic is excellently suited for the treatment of various intestinal germs and, in addition to the treatment of Helicobacter pylori, is also used for intestinal infections or infections of the genital area or urinary tract.While taking Metronidazole, it is especially important to avoid alcohol, as the accumulation of toxic substances can lead to serious consequences if taken simultaneously.

Metronidazole, like many other anntibiotics, can cause indigestion, headaches, dizziness, discomfort, discoloration of urine and allergic reactions, which should always be treated by a doctor. Healthy behavior can also improve and relieve the symptoms of the infected person. All lifestyle recommendations are preceded by a balanced lifestyle with avoidance of stress as a major factor for increased stomach acid production.

Stress is considered to be a major factor in the development of gastric mucosa inflammation in addition to the development of heart attacks. If no stress reduction is possible, learning different relaxation techniques can be helpful. As far as nutrition is concerned, it is also important to follow the instructions listed below.

Since food, similar to the presence of Helicobacter pylori, is one of the major stimuli for the production of gastric acid, optimal nutrition can also have a major influence on the course of the gastritis. For the first painful days of an inflammation of the gastric mucosa, either complete fasting or a very easily digestible, low-fat, mild full diet is recommended. Very well suited for these days are oatmeal bananas, rusk and vegetable juices.

A gentle diet should then be continued throughout the entire course of therapy. Foods that are difficult to digest and high in fat remain in the stomach for a very long time and lead to much more stomach acid production than light products that can be digested quickly in the rest of the digestive tract. On the list of foods that should not be eaten are therefore sour citrus fruits (which maintain the harmful pH value of the stomach acid due to the fruit acid), cheese, cream, fatty sauces, fried foods, cream but also sweets.

Flatulent foods such as lentils or cabbage should also be avoided, as the stomach expansion due to the gases that form is also a stimulus for the production of gastric acid. When eating vegetables, choose digestible varieties such as carrots, zucchini or salad instead of legumes. Vegetables that have been cooked beforehand become additionally digestible.

Bananas, apples, pears and apricots should also be preferred to highly acidic oranges or lemons. Meals should be divided into several small rather than a few large meals to reduce the stretching as a stimulus to stomach acid production. If the inflammation lasts longer, this diet should be maintained.

Also different beverages can strengthen the stomach acid production and should be avoided therefore. First and foremost are the drinks alcohol and coffee, which have already been mentioned several times. Similar to the flatulent cabbage, strongly carbonated drinks should not be drunk, since the gas stimulates the stomach acid production by stretching the stomach.

Highly acidic fruit juices such as orange juice also lower the pH value in addition to the stomach acid and should therefore be avoided. In principle, anything that does not cause discomfort can be eaten. According to this simple principle, the diet can later be changed to a normal diet.

The Helicobacter pylori infection is the second most common bacterial infectious disease in humans. The prevalence is much higher in developing countries than in industrialized nations. Worldwide, 50% are infected with Helicobacter pylori, but not everyone develops gastritis.

Most infections with Helicobacter pylori are asymptomatic. Non-specific symptoms such as upper abdominal pain or heartburn may also occur. The infection increases with age.

At the age of 50 years and older, every second person has Helicobacter pylori gastritis. Although some pathogenetic mechanisms of the individual Helicobacter pylori strains are known and understood, it is still not clear which strain can cause secondary diseases such as gastric ulcer and gastric cancer and which patients develop these diseases or remain asymptomatic for life. Helicobacter pylori was first described by two Western Australian researchers named Barry Marshall and John Robin Warren in 1983.

It was not until 2005 that they were awarded the Nobel Prize in Physiology or Medicine, commonly known as the Nobel Prize in Medicine, for their discovery.After Campylobacter pylori and others, it was not until 1989 that the name of the bacterium was given its current name: Helicobacter pylori. The German physician and researcher Robert Koch had already laid the foundation for the discovery of the bacterium in the 19th century, when he succeeded in cultivating bacteria in culture and, viewed under the microscope, in establishing a causal relationship with infectious diseases with bacteria as pathogens. Previously it was assumed that gastric juice would not allow harmful pathogens in an acidic environment and made psychological influences partly responsible for the development of stomach and intestinal ulcers.

The development and use of possible vaccines against infection with Helicobacter pylori are frequently discussed. Due to the high rate of infection, the unpleasant symptoms at the onset of the inflammation and the associated complications that can be caused by a Helicobacter pylori infection, such approaches are very important and topical. However, no breakthrough has yet been achieved in the development of a vaccine, and there are warnings of premature hopes for an early application.