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As of 2020, mankind has been struggling with the SARS-CoV-2 virus pandemic responsible for the development of COVID-19. Not a day goes by without the news of subsequent cases of illnesses, deaths and new variants of the pathogen on television, the Internet and radio. It therefore seems that the public awareness has become large enough to be able to fight the disease effectively. It is different in the case of antibiotic resistance, which doctors and scientists refer to as a silent pandemic of the 2050st century. The problem is more serious than previously thought. It is predicted that by 10 the number of deaths due to antibiotic resistance may reach XNUMX million.
- The overuse of antibiotics and their misuse caused many bacteria to become resistant to the effects of these drugs
- Although little is said about it, antibiotic resistance is one of the greatest problems of modern medicine. WHO is alerting that this will have huge consequences
- Are bacteriophages a chance to eliminate the problem of antibiotic resistance?
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What is antibiotic resistance?
The discovery of antibiotics was one of the turning points in the history of medicine. And like many of them, quite random.
It was 1928 when the Scottish scientist Alexander Fleming noticed that on his dish with bacteria of the genus Staphylococcus there was an unexpected mold infection Penicillium chrysogenum. The medium would probably end up in the trash, were it not for the fact that the researcher found that this accidental incident led to inhibition of the growth of bacteria cultures grown on the medium. Thus, penicillin was discovered.
It cannot be denied that the introduction of antibiotics to medicine was a milestone in the treatment of many previously incurable diseases. Their action is based, depending on their type, on the mechanisms of damaging the structures of cell membranes, as well as interfering with the synthesis of proteins and nucleic acids. However, the widespread availability of antibiotics has led many bacteria to develop resistance mechanisms to these drugs.
– The history of research on phage therapy in Poland is very long. The first, successful attempts were made before the war. It took place, inter alia, in Krakow, at the Department of Surgery of the then Jagiellonian University. Back then, bacteriophages were used to treat purulent staphylococcal infections. Interestingly, in the journals of Maria Dąbrowska *, we can read that purulent nephritis was cured in her using bacteriophages, which took place during World War II. The phages were produced at the Municipal Institute of Hygiene in Warsaw. After the war, these studies were continued, mainly on bacteriophages used to treat Escherichia coli and staphylococcal infections – explains Prof. dr hab. Antoni Różalski, head of the Department of Bacterial Biology at the University of Lodz.
Antibiotic resistance is nothing more than the resistance of bacterial pathogens to commonly used antibiotics. It has to do with the so-called bed-hedgingiem, that is, a phenomenon thanks to which bacteria develop a survival strategy even in unfavorable conditions. It is associated with the presence of special regulatory proteins. Scientists believe that such spontaneous mutations underlie the evolutionary processes of these invisible to the naked eye living creatures.
The causes of antibiotic resistance
There is no doubt that the overuse of these drugs is a major cause of antibiotic resistance. Many people accept them without scientific justification (e.g. in the course of viral infections) or simply abuse them. As it turns out, a large percentage of people are treated with antibiotics on their own, especially when they remain after the previous treatment. This is one of the key mistakes that could do more harm than good.
It is equally dangerous to take antibiotics not as prescribed by your doctor. Patients themselves stop treatment as soon as they feel better or reduce the dosage. This means that some bacteria can then remain in the body and live in it for many years, and in the event of a decrease in immunity, attack with double strength.
In Poland, as well as throughout Europe, there is an increasing resistance, especially of strains Escherichia coli, Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae i Streptococcus pneumoniae. Therefore, drugs such as Second-generation cephalosporins, vancomycin and aminoglycosides are gradually becoming less effective.
Currently, about 700 die every year due to antibiotic resistance. people. By 2050, this number is expected to increase significantly – up to 10 million per year. Such a scenario poses a real risk that diseases caused by bacteria will be a more common cause of death than cancer. Tuberculosis caused by highly antibiotic-resistant mycobacteria of the genus Mycobacterium tuberculosis.
The so-called superbugs are responsible for causing serious infections of the urinary tract, upper and lower respiratory tract, meningitis, as well as the subcutaneous tissues and the skin itself. Bacterial infections are becoming more common and can be infected very easily. Doctors emphasize that hospitals are their largest reservoirs. Surgical operations are particularly risky.
- See also: The wave of infections with the “super fungus”. Doctors fear an epidemic
Antibiotic resistance – the alarm gets louder and louder
The World Health Organization (WHO) in its reports more and more clearly emphasizes that the problem Antibiotic resistance is becoming an increasingly serious public health problem. What could the real consequences of this be? The most serious ones include:
- lack of effective treatments,
- loss of control over the number of infections and the dynamics of their spread,
- extended infection time,
- increased number of hospitalized patients due to bacterial infections (which increases health care costs),
- higher risk of a more severe course of the disease,
- higher number of deaths.
But this is not the end. The threat also affects farm animals, and thus meat consumed by humans. Monitoring the phenomenon of antibiotic resistance seems to be crucial at present to be able to fight it effectively. It is equally important to implement not only certain systemic changes in the treatment of diseases caused by bacteria, but above all to search for new solutions and develop new pharmacological strategies.
The eyes of researchers have recently been focused on bacteriophagy, and the first studies on these structures appear to be promising. Can they be seen as a chance to eliminate the problem of antibiotic resistance?
- After treatment with antibiotics, it is worth taking care of the body’s bacterial flora. Vitama Nature probiotic are live bacteria cultures that help to improve the condition of the intestinal microflora and support the work of the immune system
Bacteriophagy – vain hopes or a real chance?
A bacteriophage is a virus that can attack and kill bacteria. This is not a new discovery, as it was first described in 1915. It had a significant impact on the treatment of diseases in the so-called the pre-antibiotic era. As early as 1921, the first phage therapies were used in difficult cases of skin diseases caused by staphylococcal infections.
Due to the development of advanced research tools, the number of research on bacteriophages is constantly increasing. The mechanism of inactivation of bacteria is most often associated with the strategy of one type of bacteriophage – one type of bacterial strain. It is a fairly narrow spectrum of activity and therefore they are more effective in fighting the pathogen than commonly available pharmaceuticals.
The results of scientific research have shown that a big advantage of using phage therapies in medicine is the fact that they do not disturb the structure of the natural bacterial flora, unlike antibiotics. Moreover, a bacteriophage introduced into the body when there are no bacteria in it is quickly excreted from it, because it has no chance of multiplying.
Much of the modern research on bacteriophages is now carried out in animal models or cell cultures. A recent study at the University of California aimed at teaching (using special algorithms) bacteriophages (the method vitro) better neutralizing bacteria, including adapting to their evolution mechanisms. After many years of research, it turned out that genetically modified bacteriophages inhibited the growth of bacteria as much as 1000 times more effectively than commonly used antibiotics.
Polish scientists also make a huge contribution to the development of this field of science.
– The most famous center for phage and phage therapy in Poland is, of course, deservedly, the Institute of Immunology and Experimental Therapy of the Polish Academy of Sciences in Wrocław. Its first director, prof. Ludwik Hirszfeld pointed to the possibility of using phages, while his successor, prof. Stefan Ślopek developed this research, initially focusing on phages shigella, and then extended to other phages. This allowed for the creation of a separate phage laboratory. I think that now there are several hundred phages in the collection of this institute. In 2005, the director of the institute, prof. Andrzej Górski led to the creation of the European Center for Phage Therapy. In addition, research on phages is carried out, among others at the University of Wrocław, Warsaw University of Life Sciences, and the University of Gdańsk – says prof. dr hab. Antoni Różalski, and then adds:
– As scientists, we are looking for phages against strains resistant to antibiotics, but also able to fight bacterial biofilm. Biofilm is a form of bacterial growth on solid surfaces, e.g. epithelia, catheters or implanted replacement parts of organs. It can develop during an infection. The bacteria are then surrounded by a shell made of a biofilm matrix (which is mainly polysaccharides). We are looking for such phages that would be able to attack bacteria growing in the form of a biofilm. Why is it so important? The closure of bacteria in this biofilm significantly impedes the access of antibiotics, disinfectants and other antibacterial agents. Phage enzymes (polysaccharide depolymerase) degrade this biofilm, which facilitates access to the site of drug infection. Another challenge is creating the so-called phage cocktails – then the therapy could use not one, but two or more phages and the use of phages with antibiotics (combination therapy).
Innovative research is also carried out by the Department of Bacterial Biology at the University of Lodz.
– We got interested in phages against Proteus is wonderful. They are uropathogens that cause infections most often in catheterized people. The research is conducted in cooperation with Proteon Pharmaceuticals. We have already obtained patents for such phages. They are used in violating the biofilm structure of these bacteria. The second research we conduct takes place in cooperation with the Department of Endodontics at the Medical University of Łódź. It turns out that intra-root infections are caused by bacteria Enterococcus faecalis. They are extremely difficult to remove, also because they are resistant to chemicals and antibiotics used by dentists. Therefore, one possible method is to introduce phages there. Intensive work on characterizing them is underway – explains the research of his department Prof. dr hab. Antoni Różalski.
* Dr. Stefan Czubalski, Ph.D., a well-known and recognized urologist from Warsaw, undertook a successful therapy.