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Published on: June 28, 2024
Diversity of Endolysin Domain Architectures in Bacteriophages Infecting Bacilli
Olga N Koposova1, Olesya A Kazantseva1, Andrey M Shadrin1
1Laboratory of Bacteriophage Biology, G.K. Skryabin Institute of Biochemistry and Physiology of Microorganisms, Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences, Federal Research Center, Prospect Nauki, 5, 142290 Pushchino, Russia.
Abstract:
The increasing number of antibiotic-resistant bacterial pathogens is a serious problem in medicine. Endolysins are bacteriolytic enzymes of bacteriophages, and a promising group of enzymes with antibacterial properties. Endolysins of bacteriophages infecting Gram-positive bacteria have a modular domain organization. This feature can be used to design enzymes with new or improved properties by modifying or shuffling individual domains. This work is a detailed analysis 1of the diversity of endolysin domains found in bacteriophages infecting bacilli. During the course of the work, a database of endolysins of such bacteriophages was created, and their domain structures were analyzed using the NCBI database, RASTtk, BLASTp, HHpred, and InterPro programs. A phylogenetic analysis of endolysins was performed using MEGA X. In 438 phage genomes, 454 genes of endolysins were found. In the endolysin sequences found, eight different types of catalytic domains and seven types of cell wall binding domains were identified. The analysis showed that many types of endolysin domains have not yet been characterized experimentally. Studies of the properties of such domains will help to reveal the potential of endolysins for the creation of new antibacterial agents.
Insights
Antibiotic resistance is a growing threat. This study analyzes endolysin domains from bacteriophages infecting bacilli, identifying novel domains with potential for developing new antibacterial agents.
Area of Science:
- Microbiology
- Biochemistry
- Genomics
Background:
- Antibiotic-resistant bacterial pathogens pose a significant global health challenge.
- Bacteriophage-derived endolysins are potent antibacterial enzymes with modular structures.
- Modular endolysins offer opportunities for engineering novel antibacterial agents.
Purpose of the Study:
- To comprehensively analyze the diversity of endolysin domains in bacteriophages that infect bacilli.
- To create a database of endolysins from bacilli-infecting bacteriophages.
- To identify uncharacterized endolysin domains for future antibacterial agent development.
Main Methods:
- Bioinformatic analysis of 438 phage genomes using NCBI, RASTtk, BLASTp, HHpred, and InterPro.
- Phylogenetic analysis of endolysins using MEGA X software.
- Identification and classification of catalytic and cell wall binding domains.
Main Results:
- 454 endolysin genes were identified across 438 phage genomes.
- Eight distinct catalytic and seven distinct cell wall binding domain types were discovered.
- A significant number of identified endolysin domains remain experimentally uncharacterized.
Conclusions:
- The domain diversity in bacilli-infecting phage endolysins is substantial.
- Many endolysin domains possess unexplored potential for novel antibacterial therapies.
- Further experimental characterization of these domains is crucial for developing new antimicrobial strategies.
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