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新型靶向耐甲氧西林金黄色葡萄球菌的噬菌体MetB16:基因组特征、结构解析及治疗应用

Novel MRSA-targeting phage MetB16: Genomic features, structural insights, and therapeutic applications.

作者信息

Erdoğdu Berna, Dokuz Senanur, Güngör Görkem, Lin Wei, Tong Yigang, Özbek Tülin

机构信息

Department of Molecular Biology and Genetics, Faculty of Arts and Science, Yildiz Technical University, İstanbul, Turkiye.

College of Life Science and Technology, Beijing University of Chemical Technology, China.

出版信息

Turk J Biol. 2025 Feb 14;49(3):292-308. doi: 10.55730/1300-0152.2746. eCollection 2025.

DOI:10.55730/1300-0152.2746
PMID:40678418
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12266354/
Abstract

BACKGROUND/AIM: Recent reports have indicated that multidrug-resistant strains of S. aureus, including methicillin-resistant strains, may pose a significant threat to public health and global economic stability.

MATERIALS AND METHODS

In this study, we present the isolation and comprehensive characterization of a novel phage, derived from clinically isolated MRSA strains.

RESULTS

MetB16 exhibited an incubation period of approximately 20 min, a lysis period of around 45 min, and a burst size of 127 Plaque Forming Units (PFU)/cell. The phage demonstrated remarkable biological stability across a pH spectrum of 4.0-9.0 and maintained integrity within a temperature range of 37 and -80 °C. Scanning transmission electron microscopy and phylogenetic analyzes classified MetB16 as belonging to the Triavirus genus, representing a novel species within the Triaviruses. Whole-genome sequencing revealed a 45,295 bp-long genome size with a G + C content of 33.34%. Notably, bioinformatic analyses identified random integration sites within the MRSA genome. Functional annotation of the genome uncovered 72 open reading frames (ORFs), of which 34 encoded hypothetical proteins of unknown function, and these ORFs were associated with phage structure, packaging, host lysis, DNA metabolism, and additional functions. To elucidate the therapeutic potential of temperate phages, detailed structural analyses were conducted on key proteins, including holin, endolysin, and minor tail proteins of MetB16.

CONCLUSION

This study provides for the first time, the preliminary studies on the biological properties of MetB16 and comprehensive data facilitating an in-depth analysis of the mechanism underlying phage-host interactions, serving as a valuable reference for the evaluation of temperate phages in phage therapy.

摘要

背景/目的:最近的报告表明,金黄色葡萄球菌的多重耐药菌株,包括耐甲氧西林菌株,可能对公众健康和全球经济稳定构成重大威胁。

材料与方法

在本研究中,我们展示了从临床分离的耐甲氧西林金黄色葡萄球菌菌株中分离出的一种新型噬菌体及其全面特性。

结果

MetB16的潜伏期约为20分钟,裂解期约为45分钟,爆发量为127个噬菌斑形成单位(PFU)/细胞。该噬菌体在4.0 - 9.0的pH范围内表现出显著的生物学稳定性,并且在37℃和 - 80℃的温度范围内保持完整。扫描透射电子显微镜和系统发育分析将MetB16归类为Triavirus属,代表Triaviruses内的一个新物种。全基因组测序显示基因组大小为45,295 bp,G + C含量为33.34%。值得注意的是,生物信息学分析确定了耐甲氧西林金黄色葡萄球菌基因组内的随机整合位点。基因组的功能注释揭示了72个开放阅读框(ORF),其中34个编码功能未知的假设蛋白,这些ORF与噬菌体结构、包装、宿主裂解、DNA代谢及其他功能相关。为了阐明温和噬菌体的治疗潜力,对MetB16的关键蛋白,包括穿孔素、内溶素和小尾蛋白进行了详细的结构分析。

结论

本研究首次提供了关于MetB16生物学特性的初步研究以及有助于深入分析噬菌体 - 宿主相互作用机制的全面数据,为噬菌体疗法中温和噬菌体的评估提供了有价值的参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ef2/12266354/e0d6b6fbfef8/tjb-49-03-292f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ef2/12266354/14f1a12aedbb/tjb-49-03-292f1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ef2/12266354/2ceef5efaa76/tjb-49-03-292f5.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ef2/12266354/e0d6b6fbfef8/tjb-49-03-292f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ef2/12266354/14f1a12aedbb/tjb-49-03-292f1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ef2/12266354/2ceef5efaa76/tjb-49-03-292f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ef2/12266354/1a5c0035ccf3/tjb-49-03-292f6.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ef2/12266354/e0d6b6fbfef8/tjb-49-03-292f8.jpg

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