The emergence of antibiotic-resistant beta-hemolytic Streptococcus agalactiae strains poses increasing threat to human beings globally. As an attempt to create a novel lysin with improved activity against S. agalactiae, a chimeric lysin, ClyV, was constructed by fusing the enzymatically active domain (EAD) from PlyGBS lysin (GBS180) and the cell wall binding domain (CBD) from PlyV12 lysin (V12CBD). Plate lysis assay combined with lytic kinetic analysis demonstrated that ClyV has improved activity than its parental enzymatic domain GBS180 against multiple streptococci. Biochemical characterization showed that ClyV is active from pH 7 to 10, with the optimum pH of 9, and is stable under NaCl concentration of < 500 mM. In a S. agalactiae infection model, a single intraperitoneally administration of 0.1 mg/mouse of ClyV protected 100% mice, while it was observed that ~ 29% survive in group that received a single dose of 0.1 mg/mouse of GBS180. Moreover, a high dose of 0.8 mg/mouse ClyV did not show any adverse effects to the health or survival rate of the mice. Considering the robust bactericidal activity and good safety profile of ClyV, it represents a potential candidate for the treatment of S. agalactiae infections.

中文翻译：

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具有改善的体外和体内抗无乳链球菌杀菌活性的嵌合溶素ClyV的构建和表征。

耐药性β-溶血性无乳链球菌菌株的出现对全球人类构成越来越大的威胁。为了创建一种新型的对无乳链球菌具有增强活性的溶素，通过融合来自PlyGBS溶素（GBS180）的酶促活性域（EAD）和来自PlyV12的细胞壁结合域（CBD）来构建嵌合溶素ClyV。溶素（V12CBD）。平板裂解试验与裂解动力学分析相结合表明，ClyV的抗多种链球菌活性高于其亲本酶结构域GBS180。生化特征表明，ClyV在pH 7至10之间具有活性，最适pH为9，并且在NaCl浓度<500 mM时稳定。在无乳链球菌感染模型中，单次腹膜内施用0.1 mg /小鼠ClyV可保护100％小鼠，而观察到在接受单剂​​量0.1 mg /小鼠GBS180的组中，约有29％的患者存活。此外，高剂量0.8 mg /小鼠ClyV并未对小鼠的健康或存活率产生任何不利影响。考虑到ClyV强大的杀菌活性和良好的安全性，它代表了无乳链球菌感染的潜在治疗候选者。