Bacteriophages can be highly effective in the treatment of many infections caused by bacteria resistant to antibiotics, says Jiří Doškař
prof. RNDr. Jiří Doškař, CSc.
Head of Department – Department of Genetics and Molecular Biology
Institute of Experimental Biology
Jiří Doškař graduated in 1974 with a Degree in Biology from our faculty. He has been working here since 1978 and his research deals with the genetics and molecular biology of pathogenic staphylococci and their bacteriophages. Specifically, he studies the genetic basis of bacterial resistance to antibiotics and the spread of the genes responsible for this resistance in staphylococcal populations by means of bacteriophages. Another important area of his team’s research over the last 30 years has been the use of bacteriophages in the treatment of staphylococcal infections and the preparation and innovation of therapeutic preparations. He currently heads the Department of Genetics and Molecular Biology, where he works in the Molecular Diagnostics of Microorganisms Laboratory. He is also an expert advisor on genetically modified organisms (GMOs) for Masaryk University.
Jiří Doškař in his study. Photo: Zuzana Jayasundera
When did you become interested in natural sciences?
My interest in exploring nature manifested itself in my childhood. I kept aquarium fish, collected bugs and insects and grew cacti and other plants; I also liked chemistry. This interest continued through my primary and secondary schools, where I attended the science clubs. This contributed to my decision to study biology at the Faculty of Science of today’s Masaryk University.
What are your first memories of the faculty?
They are pleasant; I really liked that I could focus not only on biology but also on other natural sciences. I also remember that we were able to study several non-biology subjects, such as chemistry and physics, to a greater degree than present biology students can. For example, we studied a wide range of chemistry subjects, including analytical, inorganic, organic and physical chemistry. I was excited that a biological topic could be studied from different points of view through several disciplines. I really liked how all the science departments were close by in the faculty grounds at Kotlářská; this meant that it was very easy to consult with colleagues from other fields as all you had to do was go to one of the neighbouring buildings.
How would you define molecular biology, a relatively young scientific field that is presently experiencing tremendous development?
Molecular biology has been developing for the past 80 years or so. It deals with the study of biological processes in cells and organisms at the molecular level. It is dedicated to the description of biological macromolecules and their mutual functional relationships. Today, it plays an irreplaceable role in many areas important to society, such as medicine, agriculture and biotechnology, as we will discuss later.
How have molecular-biological and molecular-genetic approaches benefited biology?
They have enabled classic biological disciplines, such as botany, zoology and ecology, to reach a higher, more exact level. I remember that in the 1970s there were discussions about whether molecular biology should be a separate field within biological disciplines. Several classical biologists were against it, saying that it is more chemistry or biochemistry. Today, none of the biological fields can do without molecular biology, or rather genetics − now there is molecular microbiology, molecular virology, cell biology, molecular parasitology, molecular taxonomy… the list can be continued indefinitely. In short, without the use of molecular-biological approaches, knowledge had limits.
You have been involved in molecular biology for over 40 years. How has this field developed at our faculty?
I started as a microbiologist, but the approaches we started using at that time were already molecular-biological or molecular-genetic. I also specialised in the subject during my Diploma and a rigorous Thesis, which I prepared under the guidance of Prof. Stanislava Rosypal (*12. 6. 1927–†22. 8. 2012). After my studies, I worked for three years at the Institute of Biophysics of the then Czechoslovak Academy of Sciences in Brno. Then, Prof. Rosypal contacted me and said he would like me to come back to his laboratory and that he had a job for me. After thinking about it, I returned, and I have now been working at the faculty since 1978. The department has been renamed several times; today it operates under the name of the Department of Genetics and Molecular Biology of the Institute of Experimental Biology.
So, you started your research using new approaches. How was this new scientific field integrated into faculty’s study program?
Prof. Rosypal strove to establish molecular biology as a separate field of study and devoted an enormous amount of energy to it. However, it took quite a long time to introduce it as not everyone was in favour; after all, this science was just breaking through in our country and in Slovakia. I dedicated a considerable amount of energy and time to the preparation of this new study field; I participated in the compilation of teaching texts and introduced new methods into practical exercises. My colleagues and I then took over this field of study, today’s program, from the professor. The programs and specialisations provided by our department (e.g. the Bachelor’s Degrees in Medical Genetics and Molecular Diagnostics and Experimental and Molecular Biology) are very popular and very much in demand among applicants, not least as graduates have excellent employment prospects on the labour market.
You and your colleagues are engaged in molecular diagnostics of microorganisms. One example, we could mention is the issue of antibiotic-resistant bacteria. Antibiotic resistance is now a major health problem. Why?
Very simply, resistance of pathogenic bacteria to antibiotics means that diseases caused by such bacteria are not treatable with commonly used antibiotics. Bodies attacked by such bacteria then have less chance to overcome the infection and recover.
What exactly are you testing for antibiotic resistance?
We are investigating how resistance to antibiotics is genetically determined in bacteria. Prior to the development of methods for analysing the genetic material of bacteria (i.e. DNA), researchers used methods based on the observation of external signs and properties, i.e. phenotypes. We monitored and recorded colonies of bacteria that grew on the selection media, and whether the given strain was resistant to antibiotics. At that time, however, it was not known that there were genetic elements that condition this resistance; nor was it known that these genetic determinants (e.g. plasmids) can be transferred in different ways between individual strains, thereby rapidly spreading resistance. Today, these determinants can be easily visualised or demonstrated using a range of methods (e.g. electrophoresis, electron microscopy, PCR or hybridisation) and studied in detail. Of course, it was fascinating for me to observe how the phenotypic properties of cells can be assigned to DNA molecules at the molecular level.
Antibiotic resistance is a topic that resonates strongly in society. A study published in The Lancet (2019) shows that antibiotic resistance contributed to more than 4.95 million deaths worldwide in 2019. This makes bacterial infection the world’s third leading cause of death, after strokes and heart problems. How do you see resistance from the point of view of a molecular biologist?
Resistance is a natural feature of many bacterial species. Bacteria always live in an environment where perhaps hundreds of bacterial species coexist. Some produce antibiotics to defend themselves from other strains (which we can then get from them), and some defend themselves in a different way, always with the aim of suppressing the surrounding strains. It is one big competition. Even though antibiotics are prepared in the laboratory and used for medical purposes, bacteria have several ways they can either induce resistance to antibiotics or resist their effects. Aside from mutations, the spread of resistant determinants between different strains or species can play a huge role. This is a factor that favours the emergence of resistant pathogenic bacterial species. It is assumed that this is how resistance spreads from free-living (environmental) bacteria to the veterinary or hospital environment, where it can then be transferred to pathogenic species, and we then encounter these resistant strains.
The results of the study from The Lancet (2019) also show that as more bacteria become resistant to antibiotics, more people die from infections that were thought to be treatable. How does your research address new treatment options in cases of antibiotic resistance?
To this it must first be said that antibiotics have saved many lives. But as we said, many bacterial strains have become resistant to antibiotics. The original antibiotics were safe for the human body and had no side effects. However, as bacteria became resistant, it was necessary to develop new (so-called “stronger”) antibiotics against them − and these tend to have unpleasant side effects. They can cause allergic reactions, for example, or affect the microbiome (microbial population of the human body). That is why new possibilities for therapy are being sought and discovered. Indeed, this is the second focus of our research.
What treatment options are you looking into for cases where antibiotics no longer work?
We call it phage therapy. Some bacterial strains are naturally eliminated by bacteriophages, which are bacterial viruses that can kill these cells in a natural way. They are completely harmless to humans as they only affect bacteria. This treatment method has been known about for more than a century, and has been intensively developed in Georgia, Poland and the Czech Republic. It proved very useful during the war, for example, when phage therapy saved many people from amputation of infected limbs. Tons of phages were produced. Then the era of antibiotics began. As these were universally applicable, bacteriophages were forgotten, especially in Western countries. When the problem of antibiotic resistance arose, however, the whole world began to return to phage therapy. Legislation is currently being introduced in the EU describing in which cases and under which conditions bacteriophages can be used.
How is this topic reflected in the publications of the Laboratory of Molecular Diagnostics of Microorganisms?
The publications of our laboratory are mostly focused on pathogenic staphylococci and their bacteriophages. For example, we publish on the topic of antibiotic resistance − how it arises and how it spreads between individual strains. For many years we have been dealing with the process of transduction, where bacteriophages play an important role in the spread of resistance, which, of course, is one of their negative roles. Other bacteriophages, however, have the potential to eliminate pathogenic bacteria and can thus be used for the preparation of medicinal preparations for the therapy of infectious diseases caused by staphylococci. We have been working intensively on the preparation of safe forms for many years and have introduced many innovations in these preparations. I am glad that we cooperate with foreign workplaces and commercial companies, and that we have been lucky to have postgraduate students who achieve very high-quality results. As we cooperate with CEITEC, the Czech Collection of Microorganisms and the university hospitals in Brno, we have been able to produce several very good publications. It is impossible to obtain new original findings and publish them in quality journals without such cooperation.
And what are your prospects for the future?
Starting this year, our laboratory is joining a national project of the National Institute of Virology and Bacteriology that aims to effectively connect 28 scientific teams from the Czech Academy of Sciences and several universities, and thus improve coordination in their capacity to manage new epidemics (the Project Leader for our group is Prof. Roman Pantůček). Financial resources supplied under the EXCELES Program of the Ministry of Education, Youth and Sports funded by the European Union − Next Generation EU will enable us to further develop the issue we are dealing with. We believe that our research projects will continue to attract excellent new students and junior collaborators, allowing us to achieve even more valuable results.
Your next topic is genetically modified organisms (GMOs). You are an expert advisor for GMOs at Masaryk University. Many people realise the potential of genetic modification in connection with the production of mRNA vaccines. What is your opinion?
Today, neither biology nor medicine can do without molecular biology methods, which de facto represent methods for the analysis of genes and genomes and their modification. Such methods also extend to agriculture, industry and biotechnology. Particularly in the health sector, such methods can bring new successes in the treatment of cancer and infectious diseases. This is because genetic engineering and molecular biology methods make it possible to prepare new types of vaccines, antibodies and diagnostic kits. GMO technology has been used for many years to make plants resistant to pests or herbicides. Insulin is also a product of genetically modified bacteria. Vaccines and antibodies, however, are a relatively new area in this type of research. Nevertheless, they can be modified relatively easily and quickly as the pathogen modifies itself to escape their effects. Here, too, it is an arms race between bacteria or viruses and the preparation of medicines, as with the problem of antibiotic resistance.
How has the field of molecular biology developed during your tenure at the Institute of Experimental Biology?
All departments now use molecular biology very intensively. It is desirable that students at our institute go through classes provided by all departments, thus gaining an overview of many areas, such as microbiology, physiology and immunology of animals and plants, human biology and tumour biology. I am amazed at the state exams, the things that all students must know (and most of the time they do know😊) and how well they are prepared for practical work, whether in hospitals, agriculture or research institutes. I see a huge shift here compared to when we graduated, the material taught was much narrower in focus then.
What subjects do you teach?
I teach the Basics of Molecular Biology, I participate on half of the course in Genetic Engineering and Molecular Biology of Prokaryotes and I teach Molecular Diagnostics of Microorganisms. These are subjects that I have taught for more than 30 years, but I am gradually passing on my duties to younger colleagues.
You are the president of the Gregor Mendel Genetic Society (GSGM). What role does the society play in the field of science popularisation?
The GSGM brings together scientific research and teaching staff within the Czech Republic and Slovakia. It organises a genetic conference, for example, the last of which was held on 5−7 October 2022 at Slavkov castle near Brno. As in previous years, the conference was polythematic as the participants are all experts with research oriented in different directions. Many of the participants are teachers who come to learn about the many different areas of genetics, and they are made very welcome.
Thank you for the interview.
Translation: Kevin Roche