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Biological function identification of phage holin Hol-4086 and treatment of Staphylococcus aureus infection

文献类型： 外文期刊

作者： Zheng, Chenyu 1 ; Di, Yaxin 1 ; Wang, Yingchun 1 ; Zhao, Huyang 1 ; Wang, Ruichong 2 ; Li, Guiwei 3 ; Wang, Xiaona 1 ; San, Zhifu 1 ; Jiang, Yanping 1 ; Cui, Wen 1 ; Li, Jiaxuan 1 ; Wang, Li 1 ; Qiao, Xinyuan 1 ;

作者机构： 1.Northeast Agr Univ, Coll Vet Med, Dept Prevent Vet Med, Heilongjiang Key Lab Anim Dis Control & Pharmaceut, Harbin, Peoples R China

2.Heilongjiang Prov Ctr Dis Control & Prevent, Dept Radiol Protect, Harbin, Peoples R China

3.Heilongjiang Acad Agr Sci, Inst Rural Revitalizat Sci & Technol, Harbin, Peoples R China

关键词： Staphylococcus aureus; phage; holin; phage perforin; phage therapy

期刊名称：FRONTIERS IN MICROBIOLOGY （ 影响因子：4.5； 五年影响因子：5.2 ）

ISSN：

年卷期： 2025 年 16 卷

页码：

收录情况： SCI

摘要： The treatment of infections caused by drug-resistant Staphylococcus aureus has become increasingly difficult. In this study, the complete genome of phage 4086-1 against S. aureus was sequenced and shown to be 17,960 bp in size, with a GC content of 29.14%. Phylogenetic analysis demonstrated that phage 4086-1 exhibited a close relationship with the Staphylococcus phages SLPW, JPL-50, and LSA2366. BLAST analysis indicated that ORF12 of phage 4086-1 (termed Hol-4086) shares high identity with other reported phage-associated holins. Hol-4086 consists of 140 amino acids and exhibits high sequence identity with some members of the phage_holin_4_1 superfamily (18-125 amino acids). Hol-4086 was then expressed in Escherichia coli and detected using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western blotting. The results of a spot test demonstrated that Hol-4086 had substantial bacteriostatic effects on the host bacteria. S. aureus cells were exposed to Hol-4086 and observed using transmission electron microscopy and scanning electron microscopy. Bacterial cells treated with Hol-4086 showed ultrastructural and morphological changes. The detection of biofilm activity showed that Hol-4086 effectively inhibited and removed S. aureus biofilms. In vivo, treatment with Hol-4086 significantly reduced the number of bacteria, relieved inflammatory responses, and alleviated pathological changes in the organs of infected mice 48 h after treatment. These results demonstrate that Hol-4086 exhibits promising antibacterial potential as an alternative therapy for the treatment of infections caused by S. aureus.

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