Identification and Molecular Modification of Staphylococcus aureus Bacteriophage Lysin LysDZ25
文献类型: 外文期刊
作者: Chang, Yan 1 ; Li, Qingbin 1 ; Zhang, Shuhang 1 ; Zhang, Qing 1 ; Qi, Qingsheng 2 ; Lu, Xuemei 1 ; Liu, Yuqing 1 ;
作者机构: 1.Shandong Univ, State Key Lab Microbial Technol, Qingdao 266237, Peoples R China
2.Shandong Acad Agr Sci, Inst Anim Sci & Vet Med, Jinan 250100, Peoples R China
关键词: LysDZ25; thermal stability; lytic activity; MD simulation; MDL method
期刊名称:ACS INFECTIOUS DISEASES ( 影响因子:5.3; 五年影响因子:5.1 )
ISSN: 2373-8227
年卷期: 2023 年
页码:
收录情况: SCI
摘要: With the continuous emergence and spread of drug resistant and multi-drug-resistant Staphylococcus aureus, traditional antibiotic treatment has gradually lost its effect. There is an urgent need to develop and study new and effective bio-green inhibitors to control S. aureus. In this study, the S. aureus phage DZ25 was isolated from milk and the lysin LysDZ25 with excellent tolerance to serum and NaCl solution was identified. Subsequently, to improve the lytic activity and thermal stability of LysDZ25, RoseTTAFold was used to construct threedimensional (3D) structures, molecular dynamics (MD) simulation was used for conformational acquisition, and the MDL strategy previously developed in our lab was used to rationally design variants. After two rounds of rational design, the optimal variant with improved thermal stability, S333V/N245R/D299L, was obtained, and its half-life time was 4.0-fold that of wild-type LysDZ25. At 37, 40, 45, and 50 degrees C, the lytic activity of the optimal triple-point variant S333V/N245R/ D299L was increased by 17.3-, 26.7-, 20.2-, and 50.1-fold compared with that of the wild-type LysDZ25, respectively. Finally, cell count was used to evaluate the lytic activity, and the results showed that the optimal variant S333V/N245R/D299L could drop about 3.5 log 10 values compared with the control and about 2.6 log 10 values compared with the wild-type LysDZ25.
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