Microbiologist Matěj Bezdíček: To Vienna for experience, for a sequencer and then for an award

Matěj Bezdíček belongs to the young generation of microbiologists for whom clinical practice and research activities are obvious vessels. After graduating in experimental biology at the Faculty of Science of Masaryk University, he started his doctoral studies in oncology and haematology at the Faculty of Medicine. His thesis dealt with methods of genome analysis, and during his studies he was instrumental in patenting a method for typing bacterial strains of the intestinal bacterium E. coli. In 2023 he went to the University of Vienna to broaden his microbiological knowledge, where he spent two months thanks to the financial support from the AKTION Czech Republic - Austria programme. He started to benefit from his fresh experience immediately after his return at the Internal Hematology and Oncology Clinic of the Brno University Hospital and the Faculty of Medicine of the Medical University of Brno, and this year, for this short-term but stimulating internship, he received the award of the House of International Cooperation, which coordinates the scholarships, in the category of individuals, Participant leaving the Czech Republic.

3 Jun 2024

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In the five years since the patent was granted, where has your research focused on developing a method for typing bacterial strains?
Our patent was focused on one particular bacterium, E. coli. However, we try not to research "just in a drawer", but so that we can directly apply the results of our work in hospital practice. So the approaches we have used to develop a method targeting E. coli are being applied to other bacteria that are important to monitor in the hospital setting. In particular, these are bacteria associated with so-called nosocomial infections, i.e. those that can spread between patients or staff. These infections, otherwise known as healthcare associated infections, can complicate treatment, prolong hospital stays and place an increased financial burden on hospitals. We are working to ensure that we can catch the spread of these infections early, find their source and thus stop them more easily. At the same time, this is research that can also be used to monitor and combat the spread of bacterial resistance.

In other words, are you trying to make your method as universal as possible?
Rather, create modifications for different species of bacteria. For each species, the method targets its specific genes, which means you have to redesign the method for each new bacterium. Using the same technology and similar design procedures, but the method itself ends up being species-specific. In terms of a universal method, the current trend, especially in larger labs, is to move to whole genome sequencing of bacteria, which is again three orders of magnitude further away than what we were used to until recently. As the technology is rapidly evolving, it is also becoming cheaper and more accessible to a wider professional community. The ability to sequence bacteria is no longer the preserve of research and the largest clinical laboratories. Rather, the problem currently lies in the interpretation of the data obtained. The profession of the classical clinical microbiologist, as we know it today, will gradually disappear, because in the future it cannot do without at least basic knowledge of bioinformatics. The solution, of course, may be some specialized software that is user-friendly, but less so for the user's wallet.

“The profession of the classical clinical microbiologist, as we know it today, will gradually disappear, because in the future it cannot do without at least basic knowledge of bioinformatics.”

Matěj Bezdíček

Last year you went on a work placement in Vienna as part of the AKTION Czech Republic - Austria scholarship programme and recently you were awarded for your stay and experience by the House of Foreign Cooperation, which coordinates the programme. What inspired you to go?
With my workload, I couldn't afford to go on a "typical postdoc" for two years and leave everything behind, so a short-term internship was the only way for me to try something abroad. And actually, I didn't even have the need because I have a good background in Brno. In the end, several factors played a role. The first one was that a colleague before me had already used the same program as part of her Ph.D. studies. She even went to the same place of work, although to a different group, which opens doors for you and at the same time you see that there are people on the other side willing to dedicate themselves to you. The other factor was that my wife works at the same place at the University of Vienna, so we didn't have to go back and forth between Vienna and Brno for a while. And then the third factor was that the group I was in was one of the leading ones that was studying the microbiome and also working with the latest generation of sequencers, which we didn't have access to in Brno at the time.

What was your purpose in coming to the University of Vienna and what was your primary focus there?
The main thing for me was to learn how to work with the latest technologies, to compare them with what we use in Brno and to see if they are transferable to us. I was involved in two projects related to bacterial research, but I also looked into research on the gut microbiome, which our clinic was also interested in doing, but no one had any experience with it yet. Primarily, however, I was interested in the technical part, in order to clarify whether we were moving in the right direction in Brno and whether it was time to move on.

What conclusion did you come to? How did your work in Vienna build on what you do at your home clinic?
In our laboratory, we have primarily used second-generation sequencers for bacterial sequencing. These allow us to sequence stretches of DNA up to 300 bases long, but you never sequence the whole genome, so you lose a lot of information. The advantage of long reads is that after sequencing, you get sections that are on average ten thousand bases long or more. (Parts of the genome of most bacteria often carry genes responsible for antibiotic resistance - author's note.) We had an older version of the long-read sequencing technology before, but the data was not yet of sufficient quality. We used a combination of both approaches, long reads to build the genome skeleton and short reads to correct errors in the long reads. However, such a process is lengthy and expensive. Last year, however, a new chemistry came on the market that was available in Vienna half a year earlier than in most other labs, so there was an opportunity to go there, try it out and see if we wanted - or even needed - to continue with short reads in Brno. I found out that it doesn't, because the current technology of long readings is a big step forward in both quality and cost. Today, we can get a fifth of the price in Brno, maybe even less than before, and our outputs are better. On the basis of this assurance, we as a clinic asked for a new sequencer, with which we are now routinely working. It can be used not only for microbiological research, but it has overlap with human genetics, so that virtually the whole clinic can use it.

How would you generally compare the technical equipment and conditions at both sites?
It's hard to compare, because I came from a clinical laboratory focused on molecular biology and genetics to an academic institution like CEITEC, which has some of the most cited microbiologists in the world. So, leaving aside classical microbiology and comparing, in terms of facilities, the two laboratories within molecular microbiology, both departments are absolutely comparable and world-class. In Brno, we are also involved in research - and not a little - but our primary focus will always be on patients. On a personal level, it was interesting for me to experience the international environment and the different mentality and approach to work. Whereas here you are already at work for three hours at nine o'clock in the morning, in Vienna the "early birds" were just starting to come to work. You can tell the differences by the pace of the work and the place, for example, Americans have piles of everything on their desks because they just don't clean them up... These were things that seemed a bit strange to me coming from a clinical lab, but in a pure research lab I guess it can work differently.

“The world is moving forward very fast and if we want to move our research and its results into clinical practice, we need to make it accessible in some way.”

Matěj Bezdíček

What are your current plans and projects in which you will be able to apply your experience?
We are currently working on two projects using long-read sequencing, and in addition to this, we want to submit a third project with colleagues from the clinic, focusing on the gut microbiome of our patients and monitoring its dynamics in some new treatments. Specifically, we want to look at how the shape of the gut microbiome affects the overall patient condition over the course of treatment. As part of ongoing projects, we would like to create a user-friendly application to help with the evaluation of data obtained by whole genome sequencing of clinically relevant bacteria, targeting Czech microbiologists. As I mentioned before, a microbiologist will soon not be able to do without knowledge of bioinformatics, and if you think of a routine microbiology lab, without wishing to offend anyone, it may be staffed by doctors of an older generation who may not be fully forged in either sequencing technologies, bioinformatics or English. We need to realize that navigating the latest technologies is difficult not only for the older generation, but also for the younger ones. I'll shut myself up for a fortnight studying for attestations, and in the meantime five new sequencers come along that I hadn't heard of before. (smiles) The world is moving so fast and if we want to get our research and its results into clinical practice, we have to make it accessible in some way. And since sequencing can now be ordered as a service, we also need to focus on the ability to interpret the data. That's where our app can help, by telling you the essentials in two clicks.

Finally, how would you briefly evaluate your internship in Vienna?
For quite a long time I was afraid that my English was not good enough, that I didn't know enough in the lab, that I didn't know enough. But in the end, I can say that my experience has been nothing but positive, and at the same time I don't know anyone who had it any other way. Ultimately, it's about trying what it's like elsewhere, learning new things, and finding things that can be used in your home workplace that will take it a step forward again. I would definitely recommend a trip like this to anyone.

Matěj Bezdíček (about the fourth row from the end in the middle) among the Viennese colleagues.

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