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噬菌体溶菌酶 LysGH15 对不同葡萄球菌浮游细胞和生物膜的抗菌作用。

Antibacterial Effects of Phage Lysin LysGH15 on Planktonic Cells and Biofilms of Diverse Staphylococci.

机构信息

Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China.

Department of Clinical Laboratory, The First Hospital of Jilin University, Changchun, China.

出版信息

Appl Environ Microbiol. 2018 Jul 17;84(15). doi: 10.1128/AEM.00886-18. Print 2018 Aug 1.

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 , , , and 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 and coagulase-negative species. In the experiments, a single intraperitoneal injection of LysGH15 (20 μg/mouse) administered 1 h after the injection of at double the minimum lethal dose was sufficient to protect the mice. The 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. Most staphylococcal species are major causes of health care- and community-associated infections. In particular, is a common and dangerous pathogen, and 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 , , , and 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 efficacy of LysGH15 was demonstrated in a mouse model of bacteremia. Thus, LysGH15 exhibits therapeutic potential for treating biofilm-related or non-biofilm-related infections caused by diverse staphylococci.

摘要

治疗由葡萄球菌引起的感染变得更加困难,因为出现了多药耐药菌株以及生物膜的形成。在这项研究中,我们观察了噬菌体溶素 LysGH15 消除浮游细胞和 、 、 和 形成的生物膜的能力。所有这些菌株对 LysGH15 敏感,在使用 20 μg/ml 的 LysGH15 处理 30 分钟后,细菌计数减少了约 4 个对数单位,MIC 范围为 8 μg/ml 至 32 μg/ml。LysGH15 在 50 μg/ml 的剂量下有效地阻止了四种葡萄球菌物种的生物膜形成。在更高的剂量(100 μg/ml)下,LysGH15 对 24 小时和 72 小时形成的生物膜也表现出显著的破坏活性 和凝固酶阴性种。在体内实验中,在双最小致死剂量后 1 小时内单次腹腔注射 LysGH15(20 μg/只)足以保护小鼠。与未处理的对照组小鼠相比,用 LysGH15 处理后 24 小时,小鼠血液中的 细胞计数降低了 4 个对数单位,器官中的 细胞计数降低了 3 个对数单位。LysGH15 降低了血液中的细胞因子水平并改善了器官的病理变化。LysGH15 对浮游细胞和生物膜表现出广泛的抗葡萄球菌活性,使其成为治疗与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。大多数葡萄球菌物种是医疗保健和社区相关感染的主要原因。特别是, 是一种常见且危险的病原体, 是一种无处不在的皮肤共生菌和机会性病原体。由于多药耐药菌株的出现以及生物膜的形成,治疗葡萄球菌感染变得更加困难。在这项研究中,我们发现所有测试的 、 、 和 菌株都对噬菌体溶素 LysGH15 敏感(MIC 范围为 8 至 32 μg/ml)。更重要的是,LysGH15 不仅可以预防这些葡萄球菌形成生物膜,还可以破坏 24 小时和 72 小时的生物膜。此外,在 菌菌血症的小鼠模型中证明了 LysGH15 的疗效。因此,LysGH15 具有治疗由不同葡萄球菌引起的与生物膜相关或非生物膜相关感染的治疗潜力。

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