Identification of cell wall binding domains and repeats in Streptococcus pneumoniae phage endolysins: A molecular and diversity analysis
Streptococcus pneumoniae (pneumococcus) is a multidrug-resistant pathogen associated with pneumonia, otitis media, meningitis and other severe complications that are currently a global threat to human health. The World Health Organization listed Pneumococcus as the fourth of twelve globally prioriti...
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Elsevier
2024-12-01
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| Series: | Biochemistry and Biophysics Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405580824002085 |
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| author | Tahsin Khan Shakhinur Islam Mondal Araf Mahmud Daniyal Karim Lorraine A. Draper Colin Hill Abul Kalam Azad Arzuba Akter |
| author_facet | Tahsin Khan Shakhinur Islam Mondal Araf Mahmud Daniyal Karim Lorraine A. Draper Colin Hill Abul Kalam Azad Arzuba Akter |
| author_sort | Tahsin Khan |
| collection | DOAJ |
| description | Streptococcus pneumoniae (pneumococcus) is a multidrug-resistant pathogen associated with pneumonia, otitis media, meningitis and other severe complications that are currently a global threat to human health. The World Health Organization listed Pneumococcus as the fourth of twelve globally prioritized pathogens. Identifying alternatives to antibiotic therapies is urgently needed to combat Pneumococcus. Bacteriophage-derived endolysins can be used as alternative therapeutics due to their bacterial cell wall hydrolyzing capability. In this study, S. pneumoniae phage genomes were screened to create a database of endolysins for molecular modelling and diversity analysis of these lytic proteins. A total of 89 lytic proteins were curated from 81 phage genomes and categorized into eight groups corresponding to their different enzymatically active (EAD) domains and cell wall binding (CBDs) domains. We then constructed three-dimensional structures that provided insights into these endolysins. Group I, II, III, V, and VI endolysins showed conserved catalytic and ion-binding residues similar to existing endolysins available in the Protein Data Bank. While performing structural and sequence analysis with template lysin, an additional cell wall binding repeat was observed in Group II lysin, which was not previously known. Molecular docking performed with choline confirmed the existence of this additional repeat. Group III endolysins showed 99.16 % similarity to LysME-EF1, a lysin derived from Enterococcus faecalis. Furthermore, the comparative computational analysis revealed the existence of CBDs in Group III lysin. This study provides the first insight into the molecular and diversity analysis of S. pneumoniae phage endolysins that could be valuable for developing novel lysin-based therapeutics. |
| format | Article |
| id | doaj-art-270744f7c51e45f7a8a4ba2eed74b2c7 |
| institution | OA Journals |
| issn | 2405-5808 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biochemistry and Biophysics Reports |
| spelling | doaj-art-270744f7c51e45f7a8a4ba2eed74b2c72025-08-20T02:19:54ZengElsevierBiochemistry and Biophysics Reports2405-58082024-12-014010184410.1016/j.bbrep.2024.101844Identification of cell wall binding domains and repeats in Streptococcus pneumoniae phage endolysins: A molecular and diversity analysisTahsin Khan0Shakhinur Islam Mondal1Araf Mahmud2Daniyal Karim3Lorraine A. Draper4Colin Hill5Abul Kalam Azad6Arzuba Akter7Department of Genetic Engineering and Biotechnology, Shahjalal University of Science and Technology, Sylhet, BangladeshDepartment of Genetic Engineering and Biotechnology, Shahjalal University of Science and Technology, Sylhet, Bangladesh; Corresponding author.Department of Genetic Engineering and Biotechnology, Shahjalal University of Science and Technology, Sylhet, BangladeshDepartment of Genetic Engineering and Biotechnology, Shahjalal University of Science and Technology, Sylhet, BangladeshAPC Microbiome Ireland, University College Cork, Cork, Ireland; School of Microbiology, University College Cork, Cork, IrelandAPC Microbiome Ireland, University College Cork, Cork, Ireland; School of Microbiology, University College Cork, Cork, IrelandDepartment of Genetic Engineering and Biotechnology, Shahjalal University of Science and Technology, Sylhet, BangladeshDepartment of Biochemistry and Molecular Biology, Shahjalal University of Science and Technology, Sylhet, Bangladesh; Corresponding author.Streptococcus pneumoniae (pneumococcus) is a multidrug-resistant pathogen associated with pneumonia, otitis media, meningitis and other severe complications that are currently a global threat to human health. The World Health Organization listed Pneumococcus as the fourth of twelve globally prioritized pathogens. Identifying alternatives to antibiotic therapies is urgently needed to combat Pneumococcus. Bacteriophage-derived endolysins can be used as alternative therapeutics due to their bacterial cell wall hydrolyzing capability. In this study, S. pneumoniae phage genomes were screened to create a database of endolysins for molecular modelling and diversity analysis of these lytic proteins. A total of 89 lytic proteins were curated from 81 phage genomes and categorized into eight groups corresponding to their different enzymatically active (EAD) domains and cell wall binding (CBDs) domains. We then constructed three-dimensional structures that provided insights into these endolysins. Group I, II, III, V, and VI endolysins showed conserved catalytic and ion-binding residues similar to existing endolysins available in the Protein Data Bank. While performing structural and sequence analysis with template lysin, an additional cell wall binding repeat was observed in Group II lysin, which was not previously known. Molecular docking performed with choline confirmed the existence of this additional repeat. Group III endolysins showed 99.16 % similarity to LysME-EF1, a lysin derived from Enterococcus faecalis. Furthermore, the comparative computational analysis revealed the existence of CBDs in Group III lysin. This study provides the first insight into the molecular and diversity analysis of S. pneumoniae phage endolysins that could be valuable for developing novel lysin-based therapeutics.http://www.sciencedirect.com/science/article/pii/S2405580824002085EndolysinAlternatives to antibioticsStreptococcus pneumoniaeDrug resistance |
| spellingShingle | Tahsin Khan Shakhinur Islam Mondal Araf Mahmud Daniyal Karim Lorraine A. Draper Colin Hill Abul Kalam Azad Arzuba Akter Identification of cell wall binding domains and repeats in Streptococcus pneumoniae phage endolysins: A molecular and diversity analysis Biochemistry and Biophysics Reports Endolysin Alternatives to antibiotics Streptococcus pneumoniae Drug resistance |
| title | Identification of cell wall binding domains and repeats in Streptococcus pneumoniae phage endolysins: A molecular and diversity analysis |
| title_full | Identification of cell wall binding domains and repeats in Streptococcus pneumoniae phage endolysins: A molecular and diversity analysis |
| title_fullStr | Identification of cell wall binding domains and repeats in Streptococcus pneumoniae phage endolysins: A molecular and diversity analysis |
| title_full_unstemmed | Identification of cell wall binding domains and repeats in Streptococcus pneumoniae phage endolysins: A molecular and diversity analysis |
| title_short | Identification of cell wall binding domains and repeats in Streptococcus pneumoniae phage endolysins: A molecular and diversity analysis |
| title_sort | identification of cell wall binding domains and repeats in streptococcus pneumoniae phage endolysins a molecular and diversity analysis |
| topic | Endolysin Alternatives to antibiotics Streptococcus pneumoniae Drug resistance |
| url | http://www.sciencedirect.com/science/article/pii/S2405580824002085 |
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