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Fighting drug resistance like putting together modular furniture. Breakthrough discovery by JU scientists

Fighting drug resistance like putting together modular furniture. Breakthrough discovery by JU scientists

What do new methods of combating bacteria have in common with furniture from a popular Swedish store? The latest discoveries by researchers at the JU Małopolska Centre of Biotechnology suggest that thing is… viruses. Read on to learn more about how we can use them to treat our own diseases.

We all know that infectious diseases are caused by bacteria and viruses. However, not everyone knows that bacteria have their own viruses. Bacteriophages, as they are called, infect the cells of bacteria, often leading to their death.

What’s interesting is the fact that these ‘murderous’ viruses present a great opportunity for humanity. For several decades, we’ve been dealing with the issue of drug resistance: strains of bacteria resistant to many or even all known antibiotics are becoming an increasingly pressing problem both inside and outside of hospitals. According to the estimates, if the current trend continues, in 30 years the number of deaths caused by drug resistant bacteria could become as high as 10 million. Unable to keep up with the production of new antibiotics, humanity has been searching for alternative solutions for many years. One of them is bacteriophages.

Are we able, then, to successfully employ bacteriophages in medicine? There’s good news and bad news.

The bad news is: bacteria and bacteriophages have been locked in an evolutionary arms race for billions of years – it started long before first animal cells appeared on Earth. Billions of years of experience allowed bacteria to develop an immune system that is quite capable of defending them from bacteriophages.

The good news, however – for us, at least – is that bacteriophages are able to quickly adapt and overcome the immune system of bacteria, though we’re still not sure how. To unlock the therapeutic potential of bacteriophages, we need to better understand the ways in which they are able to successfully adjust to rapidly evolving bacterial cells.

Latest research carried out by Jagiellonian University researchers has led to surprising conclusions: bacteriophages are incredibly malleable when it comes to genetics.

Each living organism contains genetic material (genome) comprised of many genes. Genes encode information about various characteristics, such as skin or eye colour in people. ‘It’s common knowledge amongst biologists that both living organisms and viruses, which also possess genetic material, are able to shuffle their genes, exchanging them between cells. It’s a very effective evolutionary mechanism, since instead of waiting for a particular mutation, they can make use of the diverse genes all around them. It’s like in a card game: instead of keeping bad cards and hoping for your luck to change in the next round, it’s better to shuffle your hand into the deck and draw a new set. Biology invented this more than a billion years ago. In our research, we wanted to see what kind of strategy drives bacteriophages’, said Dr hab. Rafał Mostowy from the JU Małopolska Centre of Biotechnology, lead researcher in the project.

The scientists used latest tools in the area of bioinformatics to precisely compare hundreds of thousands of bacteriophage genes. After analysing the data, they saw something surprising: many different genes shared the same fragments.

‘Our research revealed that bacteriophage genes are frequently composed on separate fragments, capable of undergoing independent evolutionary processes and forming diverse combinations. This situation can also be compared to a card game, in which instead of a standard set of 52 cards we have at our disposal their fragments that can be shuffled into hundreds of unique combinations, creating completely new types of cards. This results in some genes having a much higher genetic “plasticity” and therefore being able to keep up with rapidly evolving bacteria’, added Dr hab. Rafał Mostowy.

According to research, the most malleable bacteriophage genes are the ones that encode special proteins whose purpose is to fight bacteria. These proteins are key for the development of new methods of treatment using bacteriophages to fight bacterial infections. Phage tails, specialised nano-machines capable of recognising particular bacterial strains, or endolysins, which destroy some bacterial cells by destroying a certain type of cell walls, are examples of these proteins. These discoveries offer new possibilities in designing new antibacterial methods of treatment that target harmful bacteria and protect the beneficial ones.

The results of the study also put our understanding of evolution in a new light. ‘Up until now, it was believed that genes are the fundamental units of heredity and the evolutionary process. Our research adds another layer of complexity in this area, showing that sometimes not genes, but even just their fragments can be perceived as the most basic evolutionary units’, said Dr Bogna Smug from the JU Małopolska Centre of Biotechnology, the first author of the publication.

The study could also be used in the development of new antibacterial methods of treatment. ‘Bacteriophages are very choosy and only infect certain strains of bacteria. Therefore, finding a right match is a tremendous challenge when it comes to designing treatments against drug resistant bacteria. Our research could be a watershed moment for this task. It’s like comparing ancient furniture with modern modular items that can be bought in stores today. In case of the latter, we can change their functions and purpose in the blink of an eye, while obsolete or damaged modules can be easily replaced. In the same way, antibacterial treatments could be based on rearranging gene fragments to fight a specific drug resistant strain’, added Dr Smug.

The project was funded by the Polish National Agency for Academic Exchange, National Science Centre and European Molecular Biology Organisation. The cost of publication was covered within the framework of the Excellence Initiative BioS Priority Research Area.

Link to the paper: https://www.nature.com/articles/s41467-023-43236-9

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