17. Mar. 2022

Structural virologist Pavel Plevka from CEITEC Masaryk University was the only scientist based in the Czech Republic to secure the prestigious ERC Consolidator Grant in this year´s grant competition. A total of 2,652 researchers from 42 countries across Europe have applied for a research grant to address major scientific problems, and 313 projects succeeded. Most grants went to Germany, Italy, France, the United Kingdom and Spain. Pavel Plevka, in his research project called BioPhage, will focus on the propagation of phages into a bacterial biofilm formed by golden staphylococcus cells. The aim of the project is to describe how phages enter and multiply inside the bacteria, and to explain the so far uncharacterized interactions of phages with biofilm forming bacteria under biologically and clinically relevant conditions.

Staphylococcus aureus is a pathogenic bacterium that is often associated with antibiotic resistance. In 2017, the World Health Organization (WHO) declared Staphylococcus aureus to be one of the most dangerous bacterial pathogens against which humanity urgently needs new therapeutics. Phages on the other hand, are viruses that are able to infect bacteria, and could help us to fight resistant bacteria such as Staphylococcus aureus. Phages attack bacteria, just as influenza viruses attack human cells. They attach to the surface of staphylococcus, inject their genetic information into the bacteria and the bacteria herewith becomes a factory for new phages. Bacterial infection is in this case eliminated by viral infection without harming humans. Phages are highly specialized predators and usually one type of phage attacks only a few strains of bacteria.

During human infection, Staphylococcus aureus often produces biofilm, which allows bacterial cells to better resist antibiotics and defend themselves against the human immune system. In order to fight this biofilm, long-term administration of several types of antibiotics in high doses is needed, and sometimes surgical removal of infected tissues is necessary. An alternative approach against Staphylococcus aureus could be offered by the phage therapy.  Unfortunately, the phage therapy has not been approved for clinical use, because the effects of phage infection on a biofilm are not yet sufficiently characterized. Pavel Plevka and his research team have been studying bacteriophages for several years and will now focus on a detailed study of a phage called phi812, which seems to be the most suitable type of phage for fighting staphylococcus aureus.

"My research project will focus on understanding the dynamics of phage infection of the biofilm and the molecular details of the subsequent multiplication of phages in Staphylococcus aureus host cells," explains Pavel Plevka. "One has to consider that the bacteriophage is 5,000 times smaller than the head of a pin and we plan to characterize how phages are assembled from individual components and how phage infection spreads through the biofilm, and for this we will have to use a combination of advanced microscopic techniques," adds Plevka.

"We will use light sheet microscopy to observe biofilm development and the course of phage infections. With the help of cryo-electron microscopy, we will look at the formation of phage particles in infected cells," explains Pavel Plevka. This innovative approach, which combines several microscopic approaches, will allow for the observation of a phage continuously for several days during the biofilm penetration process. It will help researchers to finally determine how cells in a biofilm prevent phage infection and whether Staphylococcus aureus could reach herd immunity against the phage infection. A part of the biofilm will be fixated for subsequent correlative analysis by electron microscopy, and this will enable researchers to find out with what particular cells of the golden staphylococcus the phage directly interacts.

"The ERC grant means generous funding for five years combined with the absence of requirements for a certain number of publications. We can thus afford to concentrate on very complex projects that may not succeed. The risk of failure is balanced by the hope that we will discover interesting things about the phages and the bacterial biofilm. Our research could contribute to solving the growing threat of antibiotic resistance of pathogenic bacteria," concludes Pavel Plevka.

Pavel Plevka received the ERC Starting Grant for Early Stage Researchers in 2013, and became herewith the first scientist with an ERC grant in Brno. This ERC grant of Pavel Plevka is already the tenth ERC grant at Masaryk University. Plevka's first ERC grant focused on the study of human picornaviruses. These two projects are not related, but both are based on the research domain of Pavel Plevka, which is the structural biology of viral particles and the use of cryo-electron microscopy.

"I am very pleased with another success of Pavel Plevka, who is not only a great scientist but also a very effective research manager, and this is a guarantee that this new project will certainly bring results that will push the boundaries of current knowledge even further," says Jiří Nantl, Director of CEITEC Masaryk University.

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