{"title":"鉴定肺炎链球菌噬菌体内溶菌素的细胞壁结合域和重复序列:分子和多样性分析","authors":"","doi":"10.1016/j.bbrep.2024.101844","DOIUrl":null,"url":null,"abstract":"<div><div><em>Streptococcus pneumoniae</em> (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 <em>Pneumococcus</em> as the fourth of twelve globally prioritized pathogens. Identifying alternatives to antibiotic therapies is urgently needed to combat <em>Pneumococcus</em>. Bacteriophage-derived endolysins can be used as alternative therapeutics due to their bacterial cell wall hydrolyzing capability. In this study, <em>S. pneumoniae</em> 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 <em>Enterococcus faecalis</em>. 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 <em>S. pneumoniae</em> phage endolysins that could be valuable for developing novel lysin-based therapeutics.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":null,"pages":null},"PeriodicalIF":2.3000,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Identification of cell wall binding domains and repeats in Streptococcus pneumoniae phage endolysins: A molecular and diversity analysis\",\"authors\":\"\",\"doi\":\"10.1016/j.bbrep.2024.101844\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div><em>Streptococcus pneumoniae</em> (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 <em>Pneumococcus</em> as the fourth of twelve globally prioritized pathogens. Identifying alternatives to antibiotic therapies is urgently needed to combat <em>Pneumococcus</em>. Bacteriophage-derived endolysins can be used as alternative therapeutics due to their bacterial cell wall hydrolyzing capability. In this study, <em>S. pneumoniae</em> 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 <em>Enterococcus faecalis</em>. 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 <em>S. pneumoniae</em> phage endolysins that could be valuable for developing novel lysin-based therapeutics.</div></div>\",\"PeriodicalId\":8771,\"journal\":{\"name\":\"Biochemistry and Biophysics Reports\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2024-10-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biochemistry and Biophysics Reports\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2405580824002085\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biochemistry and Biophysics Reports","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2405580824002085","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
肺炎链球菌(肺炎球菌)是一种具有多重耐药性的病原体,与肺炎、中耳炎、脑膜炎和其他严重并发症有关,是目前威胁人类健康的全球性疾病。世界卫生组织将肺炎球菌列为十二种全球优先病原体中的第四种。目前迫切需要找到抗生素疗法的替代品来抗击肺炎球菌。噬菌体衍生的内溶素具有水解细菌细胞壁的能力,可用作替代疗法。在这项研究中,对肺炎双球菌噬菌体基因组进行了筛选,以建立一个内溶菌素数据库,用于这些溶菌蛋白的分子建模和多样性分析。我们从 81 个噬菌体基因组中筛选出 89 种溶菌酶蛋白,并根据其不同的酶活性(EAD)结构域和细胞壁结合(CBDs)结构域将其分为八组。然后,我们构建了三维结构,以便深入了解这些内溶菌素。第一组、第二组、第三组、第五组和第六组内溶酶原显示出保守的催化和离子结合残基,与蛋白质数据库中现有的内溶酶原相似。在对模板溶菌素进行结构和序列分析时,在第二组溶菌素中发现了一个额外的细胞壁结合重复序列,这在以前是不为人知的。与胆碱进行的分子对接证实了这一额外重复的存在。第 III 组溶菌素与粪肠球菌的溶菌素 LysME-EF1 的相似度为 99.16%。此外,比较计算分析表明,第 III 组溶菌酶中存在 CBD。这项研究首次揭示了肺炎双球菌噬菌体内溶菌素的分子和多样性分析,对开发基于溶菌素的新型疗法很有价值。
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 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.
期刊介绍:
Open access, online only, peer-reviewed international journal in the Life Sciences, established in 2014 Biochemistry and Biophysics Reports (BB Reports) publishes original research in all aspects of Biochemistry, Biophysics and related areas like Molecular and Cell Biology. BB Reports welcomes solid though more preliminary, descriptive and small scale results if they have the potential to stimulate and/or contribute to future research, leading to new insights or hypothesis. Primary criteria for acceptance is that the work is original, scientifically and technically sound and provides valuable knowledge to life sciences research. We strongly believe all results deserve to be published and documented for the advancement of science. BB Reports specifically appreciates receiving reports on: Negative results, Replication studies, Reanalysis of previous datasets.