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UW researchers identify a phage-derived enzyme that may help combat drug-resistant Klebsiella pneumoniae

Researchers from the Faculty of Biology at the University of Warsaw, in collaboration with scientists from the University of Wrocław, have described a phage-derived enzyme that effectively weakens the dangerous bacterium Klebsiella pneumoniae. The findings, published in Emerging Microbes & Infections, show that this compound may become a starting point for the development of new strategies to combat antibiotic-resistant bacteria.

The growing rise of antibiotic resistance, that is, the ability of bacteria to withstand the action of antibiotics, is now one of the most serious challenges in modern medicine. One of the most promising directions in the search for new therapies involves bacteriophages — viruses that naturally infect bacteria. A particularly dangerous pathogen is Klebsiella pneumoniae, a hospital-associated bacterium that causes severe and difficult-to-treat infections, including pneumonia, especially in vulnerable patients.

The aim of the study was to identify and characterize a bacteriophage-derived enzyme capable of degrading the capsular polysaccharide of K. pneumoniae. This capsule protects the bacterium against the host immune system and supports its survival within the host organism.

In the first stage of the study, the researchers identified in the phage genome a gene potentially encoding the enzyme of interest and then, using bioinformatic tools, predicted its possible function and structure. In the next step, using bioengineering methods, they introduced the gene encoding this enzyme into E. coli in order to produce the protein under laboratory conditions. After purification, the protein was used in further experiments.

The researchers examined the enzyme’s effect on the bacterial capsule and on the ability of the bacteria to form biofilm, a complex structure that increases bacterial resistance to treatment and facilitates colonization. They also investigated how enzyme-treated bacteria behaved in contact with lung cells and how they responded to innate immune mechanisms, particularly to the action of components present in human serum. The protective effect of the enzyme was also assessed in a simple infection model using greater wax moth larvae.

The authors showed that the enzyme, named PRA33gp45, acts specifically and efficiently degrades the capsular polysaccharide of the tested bacterium. It also markedly inhibited biofilm formation and weakened already established biofilm. In addition, it altered the way the bacteria interacted with host cells, limiting their ability to survive inside cells. In the larval model, the enzyme significantly improved survival after infection, especially when the bacteria had been pre-exposed to the enzyme.

The identification of this enzyme and the demonstration of its activity against pathogenic K. pneumoniae contribute to the development of new antibacterial therapies and broaden our knowledge of how phage-derived enzymes may be used in the fight against dangerous antibiotic-resistant bacteria.

The authors of the study from the Faculty of Biology are: Magdalena Pełka, MSc, and Weronika Czekała, MSc (co-first authors), Agnieszka Kwiatek, DSc, Marta Polańska, PhD, Piotr Golec, DSc, Agnieszka Wyszyńska, DSc, and Monika Adamczyk-Popławska, DSc (corresponding author).

The study was funded by the PRELUDIUM BIS grant from the National Science Centre, no. 2021/43/O/NZ6/00379, and by the Excellence Initiative – Research University project of the University of Warsaw, no. IDUB-622-649/2024.

Publication link: https://doi.org/10.1080/22221751.2026.2645857

We warmly congratulate the authors!