Prophage Lysin Ply30 Protects Mice from Streptococcus suis and Streptococcus equi subsp. zooepidemicus Infections
Prophage Lysin Ply30 Protects Mice from Streptococcus suis and Streptococcus equi subsp. zooepidemicus Infections
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DOI：
10.1128/aem.02300-15
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发表时间：
2015-08
影响因子：
4.4
通讯作者：
F. Tang;Dezhi Li;Haojin Wang;Zhe Ma;Chengping Lu;Jianjun Dai
中科院分区：
文献类型：
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作者：
F. Tang;Dezhi Li;Haojin Wang;Zhe Ma;Chengping Lu;Jianjun Dai
摘要猪链球菌和马链球菌亚种。动物寄生虫能够感染人类和各种动物，对世界范围的养猪业造成严重的问题。随着抗生素耐药性的增加，由β-内酰胺酶编码的溶酶体酶已显示出用于对抗病原菌的潜力。本研究中，一种新的噬菌体溶素Ply 30，由S.重组表达并纯化了猪原噬菌体phi 30 c。Ply 30对S. suis和S.马链球菌离体动物模型。对于大多数测试的S，在600 nm处的光密度（OD 600）与未处理的OD 600的比率。suis和S.马链球菌在1h内，鼠伤寒沙门氏菌菌株数分别从1降至<0.3和<0.5。平板活力测定结果表明，处理后的细菌在1小时内CFU减少1- 2-log。Ply 30的最适浓度为50 μg/ml，最适pH为7。此外，Ply 30在宽pH范围（pH 6至10）内保持高活性。Ply 30对链球菌属菌株的MIC范围为16 - 512 μg/ml。在体内，2 mg剂量的Ply 30保护90%（9/10小鼠）的小鼠免受S.马链球菌80%（8/10）的小鼠感染S.猪。7天后，溶素Ply 30治疗，细菌负荷显着降低，在所有测试的器官和血液相比，在1小时感染后没有Ply 30治疗。Ply 30在体外和体内均表现出抗菌效果，并保护小鼠免受两种细菌感染，表明Ply 30可能是一种有效的抗链球菌治疗剂。
ABSTRACT Streptococcus suis and Streptococcus equi subsp. zooepidemicus are capable of infecting humans and various animals, causing significant problems for the worldwide swine industry. As antibiotic resistance has increased, lysosomal enzymes encoded by phages have shown potential for use against pathogenic bacteria. In this study, a novel bacteriophage lysin, Ply30, encoded by the S. suis prophage phi30c, was recombinantly expressed and purified. Ply30 showed high bacteriolysis activity on S. suis and S. equi subsp. zooepidemicus in vitro. The ratio of the optical density at 600 nm (OD600) with treatment versus the OD600 with no treatment for most tested S. suis and S. equi subsp. zooepidemicus strains decreased from 1 to <0.3 and <0.5, respectively, within 1 h. The results of plate viability assays showed that treated bacteria suffered a 1- to 2-log decrease in CFU within 1 h. The optimal concentration of Ply30 was 50 μg/ml, and the optimal pH was 7. Moreover, Ply30 maintained high activity over a wide pH range (pH 6 to 10). The MICs of Ply30 against Streptococcus strains ranged from 16 to 512 μg/ml. In vivo, a 2-mg dose of Ply30 protected 90% (9/10 mice) of mice from infection with S. equi subsp. zooepidemicus and 80% (8/10 mice) of mice from infection with S. suis. Seven days after lysin Ply30 treatment, bacterial loads were significantly decreased in all tested organs and blood compared with those at 1 h postinfection without Ply30 treatment. Ply30 showed in vitro and in vivo antimicrobial efficiency and protected mice against two kinds of bacterial infections, indicating that Ply30 may be an effective therapeutic against streptococci.