目的:链球菌属包含重要的人畜共患病原体,例如引起牛乳腺炎的病原体。不幸的是,许多链球菌已经产生了抗生素耐药性。噬菌体溶素被认为是抗生素的有希望的替代品,因为细菌很难产生溶素抗性。然而,仍然缺乏用于治疗链球菌诱导的乳腺炎的噬菌体溶素资源。
方法:我们从猪链球菌SS0859菌株的基因组中鉴定了原蛋白酶Lys0859。随后对Lys0859进行了表征,以确定其宿主范围,MIC,牛奶中的杀菌活性,和体外清除生物膜的能力。最后,为了确定Lys0859在体内治疗牛乳腺炎和猪链球菌感染的效果,我们建立了无乳链球菌ATCC13813诱导的乳腺炎和猪链球菌血清型2SC19全身感染的模型。
结果:我们的结果表明,Lys0859对从患有牛乳腺炎的动物中分离的链球菌和葡萄球菌以及从猪中分离的猪链球菌的15种血清型具有广谱裂解活性。与PBS组相比,乳腺内和肌肉注射Lys0859使乳腺组织中的细菌数量减少了3.75和1.45log,分别。此外,感染后1小时腹膜内施用100μg/小鼠的Lys0859可保护83.3%(5/6)的小鼠免受致死剂量的猪链球菌感染。
结论:总体而言,我们的研究结果提高了对对抗链球菌诱导的乳腺炎和猪链球菌感染的新策略的理解和开发.
The genus Streptococcus contains species of important zoonotic pathogens such as those that cause bovine mastitis. Unfortunately, many Streptococcus species have developed antibiotic resistance. Phage lysins are considered promising alternatives to antibiotics because it is difficult for bacteria to develop lysin resistance. However, there remains a lack of phage lysin resources for the treatment of streptococci-induced mastitis.
We identified the prophage lysin Lys0859 from the genome of the Streptococcus suis SS0859 strain. Lys0859 was subsequently characterized to determine its host range, MIC, bactericidal activity in milk, and ability to clear biofilms in vitro. Finally, to determine the effects of Lys0859 on the treatment of both bovine mastitis and S. suis infection in vivo, we established models of Streptococcus agalactiae ATCC 13813-induced mastitis and S. suis serotype 2 SC19 systemic infection.
Our results demonstrate that Lys0859 possesses broad-spectrum lytic activity against Streptococcus and Staphylococcus species isolated from animals with bovine mastitis and 15 serotypes of S. suis isolated from swine. Intramammary and intramuscular injection of Lys0859 reduced the number of bacteria in mammary tissue by 3.75 and 1.45 logs compared with the PBS group, respectively. Furthermore, 100 μg/mouse of Lys0859 administered intraperitoneally at 1 h post-infection protected 83.3% (5/6) of mice from a lethal dose of S. suis infection.
Overall, our results enhance the understanding and development of new strategies to combat both streptococci-induced mastitis and S. suis infection.