LysSYL: a broad-spectrum phage endolysin targeting Staphylococcus species and eradicating S. aureus biofilms

被引：14

作者：

Liu, He ^{[1
]}

Wei, Xuemei ^{[2
]}

Wang, Zhefen ^{[3
]}

Huang, Xiaonan ^{[1
]}

Li, Mengyang ^{[4
]}

Hu, Zhen ^{[1
]}

Zhang, Kexin ^{[5
]}

Hu, Qiwen ^{[1
]}

Peng, Huagang ^{[1
]}

Shang, Weilong ^{[1
]}

Yang, Yi ^{[1
]}

Wang, Yuting ^{[1
]}

Lu, Shuguang ^{[1
]}

Rao, Xiancai ^{[1
,2
]}

机构：

[1] Army Med Univ, Key Lab Microbial Engn Educ Comm Chongqing, Coll Basic Med Sci, Dept Microbiol, Chongqing 400038, Peoples R China

[2] Southwest Univ, Med Res Inst, Chongqing 400700, Peoples R China

[3] Kunming Med Univ, Affiliated Hosp 1, Dept Neurol, Kunming 650032, Yunnan, Peoples R China

[4] Chongqing Univ, Sch Med, Dept Microbiol, Chongqing 400044, Peoples R China

[5] Southwest Univ, Med Res Inst, Immunol Res Ctr, Chongqing 400700, Peoples R China

来源：

MICROBIAL CELL FACTORIES | 2024年 / 23卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Phage; Endolysin; Staphylococcus aureus; Biofilms; Persisters; RESISTANT; THERAPY; FUTURE;

D O I：

10.1186/s12934-024-02359-4

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Background Staphylococcus aureus and its single or mixed biofilm infections seriously threaten global public health. Phage therapy, which uses active phage particles or phage-derived endolysins, has emerged as a promising alternative strategy to antibiotic treatment. However, high-efficient phage therapeutic regimens have yet to be established. Results In this study, we used an enrichment procedure to isolate phages against methicillin-resistant S. aureus (MRSA) XN108. We characterized phage SYL, a new member of the Kayvirus genus, Herelleviridae family. The phage endolysin LysSYL was expressed. LysSYL demonstrated stability under various conditions and exhibited a broader range of efficacy against staphylococcal strains than its parent phage (100% vs. 41.7%). Moreover, dynamic live/dead bacterial observation demonstrated that LysSYL could completely lyse MRSA USA300 within 10 min. Scan and transmission electron microscopy revealed evident bacterial cell perforation and deformation. In addition, LysSYL displayed strong eradication activity against single- and mixed-species biofilms associated with S. aureus. It also had the ability to kill bacterial persisters, and proved highly effective in eliminating persistent S. aureus when combined with vancomycin. Furthermore, LysSYL protected BALB/c mice from lethal S. aureus infections. A single-dose treatment with 50 mg/kg of LysSYL resulted in a dramatic reduction in bacterial loads in the blood, liver, spleen, lungs, and kidneys of a peritonitis mouse model, which resulted in rescuing 100% of mice challenged with 108 colony forming units of S. aureus USA300. Conclusions Overall, the data provided in this study highlight the strong therapeutic potential of endolysin LysSYL in combating staphylococcal infections, including mono- and mixed-species biofilms related to S. aureus.

引用

页数：19

共 59 条

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