Eternal battle of Bacteria and their Viruses
In July six bilateral projects carried out by Polish scientists in collaboration with teams from Belgium-Flanders received a total of 9.5 million Polish zloty in funding from the National Science Centre (NCN). Among them is the project led by our researcher, prof. dr hab. Zuzanna Drulis-Kawa, who became the laureate of OPUS 24+LAP.
The researcher will carry out a project related to bacteriophages (bacterial viruses) and their utilization in combating multidrug-resistant pathogens (MDR). Her Belgian-Flemish partner will be professor Yves Briers from Ghent University. The team will also collaborate with professor Stan Brouns from Delft University of Technology in the Netherlands, who will bring unique knowledge about bacterial resistance. The scientists will focus on examining the characteristics and functionalities of so-called jumbo phages that infect Klebsiella bacteria. The particles of these viruses can be equipped with several/enzymatically active receptor-binding proteins (RBPs), enabling them to infect many strains belonging to the Klebsiella species. Therefore, they are highly attractive from a therapeutic standpoint. Phage therapy has been a long-known concept, but it has only recently gained significant interest. Phages can be used instead of or in combination with antibiotics in the treatment of bacterial infections.
The research will Focus on the following:
Since the mortality rate due to infections caused by MDR (multidrug-resistant) Klebsiella pneumoniae strains is dramatically increasing without traditional therapeutic options, the World Health Organization has designated this bacterium as a Priority 1 (critical) pathogen. Therefore, finding alternative and effective therapies is of paramount importance.
The primary virulence factor of Klebsiella is its polysaccharide capsule, which enables it to evade the human immune system’s response. This bacterium can produce over eighty different types of capsular structures, making it particularly challenging to find effective anti-virulence/antibacterial agents.
Bacteriophages (phages) recognize and kill their bacterial hosts with very high specificity. Each phage infection is initiated by the recognition of a specific structure on the bacterial surface (called a receptor) by a receptor-binding protein (RBP), which is part of the phage particle. Some phages infect a narrow range of bacterial hosts, while others can attack a broad spectrum of them using different RBPs. An interesting example is jumbo phages that attack rod-shaped bacteria.
Klebsiella, which are equipped with numerous RBPs (Receptor-Binding Proteins) forming a flower-like structure and specifically degrading various types of capsules.
Most jumbo phages have only been discovered recently, and many aspects of their functionality and biology remain unknown. One important aspect is how their complex, flower-like RBP structure is organized, functions, evolves, and how the bacterial host avoids jumbo phage infection. In this project, the above-mentioned issues will be investigated using two model jumbo phages of Klebsiella (KAN and fKp24). Employing advanced molecular microbiology, synthetic biology, and structural methods, these complex aspects will be analyzed at the level of proteins, phage particles, and in bacterial-phage interactions,” says professor Zuzanna Drulis-Kawa from the Department of Pathogen Biology and Immunology, Faculty of Biological Sciences, University of Wrocław.
The researchers aim to answer four specific questions:
-What is the overall organisation of highly branched RBP systems in jumbo phages and how do they function?
-Are highly branched RBP systems in jumbo phages static or dynamic?
-How do highly branched RBP systems evolve in jumbo phages?
-How do bacteria defend themselves against infection by jumbo phages equipped with highly branched RBP systems?
“With the scientific experience we have gained so far regarding RBPs of Klebsiella phages, we will introduce state-of-the-art research methods to expand fundamental knowledge about the biology of jumbo phages,” says our researcher, professor Zuzanna Drulis-Kawa. Unraveling the organization, dynamics, and evolution of flower-like RBP systems in jumbo phages will serve as the basis for identifying and developing modern phage preparations that are effective in combating infections caused by MDR K. pneumoniae strains. Although the project focuses on basic research, its results will have significant economic and social impact, especially in the public health sector.
Translated by Florentyna Sołtysiak (student of English Studies at the University of Wrocław) as part of the translation practice.
