Antibacterial Effects of Phage Lysin LysGH15 on Planktonic Cells and Biofilms of Diverse Staphylococci
Antibacterial Effects of Phage Lysin LysGH15 on Planktonic Cells and Biofilms of Diverse Staphylococci
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噬菌体赖氨酸LysGH15对多种葡萄球菌浮游细胞和生物膜的抗菌作用
DOI：
10.1128/aem.00886-18
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发表时间：
2018
影响因子：
4.4
通讯作者：
Jingmin Gu
中科院分区：
文献类型：
--
作者：
Yufeng Zhang;Mengjun Cheng;Hao Zhang;Jiaxin Dai;Zhimin Guo;Xinwei Li;Yalu Ji;Ruopeng Cai;Hengyu Xi;Xinwu Wang;Yibing Xue;Changjiang Sun;Xin Feng;Liancheng Lei;Wenyu Han;Jingmin Gu
大多数葡萄球菌是卫生保健和社区相关感染的主要原因。特别是，金黄色葡萄球菌是一种常见且危险的病原体，而表皮葡萄球菌是一种普遍存在的皮肤共生性和机会性病原体。由于多重耐药菌株的出现以及生物被膜的形成，葡萄球菌引起的感染的治疗变得更加困难。在本研究中，我们发现所有被测试的金黄色葡萄球菌、表皮葡萄球菌、溶血葡萄球菌和人葡萄球菌对噬菌体裂解酶LysGH15(MIC8~32μg/ml)都很敏感。更重要的是，LysGH15不仅阻止了这些葡萄球菌生物膜的形成，而且还破坏了24小时和72小时的生物膜。此外，LysGH15在表皮葡萄球菌菌血症小鼠模型中的体内疗效被证明。因此，LysGH15在治疗由各种葡萄球菌引起的生物膜相关或非生物膜相关感染方面显示出治疗潜力。摘要由于多重耐药菌株的出现和生物被膜的形成，葡萄球菌感染的治疗变得更加困难。在本研究中，我们观察了噬菌体裂解酶LysGH15对金黄色葡萄球菌、表皮葡萄球菌、溶血葡萄球菌和人葡萄球菌形成的浮游葡萄球菌和生物膜的清除能力。所有菌株均对LysGH15敏感，20μg/mlLysGH15作用30min内细菌数下降约4log单位，MIC为8~32μg/ml，50μg/mlLysGH15可有效抑制4种葡萄球菌生物被膜的形成，较高剂量(100μg/ml)时，LysGH15对金黄色葡萄球菌和凝固酶阴性菌所形成的24 h和72 h生物膜也有显著的破坏作用。在体内实验中，在注射表皮葡萄球菌后1h单次腹腔注射LysGH15(20μg/只)，剂量是最小致死量的两倍，足以保护小鼠。经LysGH15处理后24 h，小鼠血液中表皮葡萄球菌细胞数比未处理对照组小鼠低4个对数单位，器官中表皮葡萄球菌细胞数低3个对数单位。LysGH15降低了血液中的细胞因子水平，改善了器官的病理变化。LysGH15对浮游细胞和生物膜具有广泛的抗葡萄球菌活性，这使得LysGH15成为生物膜相关或非生物膜相关葡萄球菌感染的有价值的治疗选择。重要性大多数葡萄球菌是卫生保健和社区相关感染的主要原因。特别是，金黄色葡萄球菌是一种常见且危险的病原体，而表皮葡萄球菌是一种普遍存在的皮肤共生性和机会性病原体。由于多重耐药菌株的出现以及生物被膜的形成，葡萄球菌引起的感染的治疗变得更加困难。在本研究中，我们发现所有被测试的金黄色葡萄球菌、表皮葡萄球菌、溶血葡萄球菌和人葡萄球菌对噬菌体裂解酶LysGH15(MIC8~32μg/ml)都很敏感。更重要的是，LysGH15不仅阻止了这些葡萄球菌生物膜的形成，而且还破坏了24小时和72小时的生物膜。此外，LysGH15在表皮葡萄球菌菌血症小鼠模型中的体内疗效被证明。因此，LysGH15在治疗由各种葡萄球菌引起的生物膜相关或非生物膜相关感染方面显示出治疗潜力。
Most staphylococcal species are major causes of health care- and community-associated infections. In particular, Staphylococcus aureus is a common and dangerous pathogen, and Staphylococcus epidermidis is a ubiquitous skin commensal and opportunistic pathogen. Treatment of infections caused by staphylococci has become more difficult because of the emergence of multidrug-resistant strains as well as biofilm formation. In this study, we found that all tested S. aureus, S. epidermidis, Staphylococcus haemolyticus, and Staphylococcus hominis strains were sensitive to the phage lysin LysGH15 (MICs ranging from 8 to 32 μg/ml). More importantly, LysGH15 not only prevented biofilm formation by these staphylococci but also disrupted 24-h and 72-h biofilms. Furthermore, the in vivo efficacy of LysGH15 was demonstrated in a mouse model of S. epidermidis bacteremia. Thus, LysGH15 exhibits therapeutic potential for treating biofilm-related or non-biofilm-related infections caused by diverse staphylococci. ABSTRACT Treatment of infections caused by staphylococci has become more difficult because of the emergence of multidrug-resistant strains as well as biofilm formation. In this study, we observed the ability of the phage lysin LysGH15 to eliminate staphylococcal planktonic cells and biofilms formed by Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus, and Staphylococcus hominis. All these strains were sensitive to LysGH15, showing reductions in bacterial counts of approximately 4 log units within 30 min after treatment with 20 μg/ml of LysGH15, and the MICs ranged from 8 μg/ml to 32 μg/ml. LysGH15 efficiently prevented biofilm formation by the four staphylococcal species at a dose of 50 μg/ml. At a higher dose (100 μg/ml), LysGH15 also showed notable disrupting activity against 24-h and 72-h biofilms formed by S. aureus and coagulase-negative species. In the in vivo experiments, a single intraperitoneal injection of LysGH15 (20 μg/mouse) administered 1 h after the injection of S. epidermidis at double the minimum lethal dose was sufficient to protect the mice. The S. epidermidis cell counts were 4 log units lower in the blood and 3 log units lower in the organs of mice 24 h after treatment with LysGH15 than in the untreated control mice. LysGH15 reduced cytokine levels in the blood and improved pathological changes in the organs. The broad antistaphylococcal activity exerted by LysGH15 on planktonic cells and biofilms makes LysGH15 a valuable treatment option for biofilm-related or non-biofilm-related staphylococcal infections. IMPORTANCE Most staphylococcal species are major causes of health care- and community-associated infections. In particular, Staphylococcus aureus is a common and dangerous pathogen, and Staphylococcus epidermidis is a ubiquitous skin commensal and opportunistic pathogen. Treatment of infections caused by staphylococci has become more difficult because of the emergence of multidrug-resistant strains as well as biofilm formation. In this study, we found that all tested S. aureus, S. epidermidis, Staphylococcus haemolyticus, and Staphylococcus hominis strains were sensitive to the phage lysin LysGH15 (MICs ranging from 8 to 32 μg/ml). More importantly, LysGH15 not only prevented biofilm formation by these staphylococci but also disrupted 24-h and 72-h biofilms. Furthermore, the in vivo efficacy of LysGH15 was demonstrated in a mouse model of S. epidermidis bacteremia. Thus, LysGH15 exhibits therapeutic potential for treating biofilm-related or non-biofilm-related infections caused by diverse staphylococci.