LysGH15, a Novel Bacteriophage Lysin, Protects a Murine Bacteremia Model Efficiently against Lethal Methicillin-Resistant Staphylococcus aureus Infection
LysGH15, a Novel Bacteriophage Lysin, Protects a Murine Bacteremia Model Efficiently against Lethal Methicillin-Resistant Staphylococcus aureus Infection
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DOI：
10.1128/jcm.01144-10
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发表时间：
2011-01-01
影响因子：
9.4
通讯作者：
Han, Wenyu
中科院分区：
文献类型：
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作者：
Gu, Jingmin;Xu, Wei;Han, Wenyu
噬菌体编码的溶素是一种破坏细菌细胞壁的酶。噬菌体溶素可以替代传统的抗生素治疗对多种抗生素耐药的病原体。本研究分离了一株新型葡萄球菌噬菌体GH 15，并表达和纯化了内源性裂解酶（LysGH 15）。溶素LysGH 15显示出广泛的裂解谱，体外治疗可迅速和完全杀死许多金黄色葡萄球菌菌株，包括耐甲氧西林的S。金黄色葡萄球菌（MRSA）。在动物实验中，在MRSA注射后1小时以最小致死剂量的两倍单次腹膜内注射LysGH 15（50 μ g）足以保护小鼠（P < 0.01）。未受保护小鼠的菌血症在攻击后3.5小时内达到约10（7）CFU/ml的菌落计数，而赖氨酸保护小鼠的平均菌落计数低于10（4）CFU/ml（最终无法检测到）。这些结果表明，LysGH 15可以杀死S.金黄色葡萄球菌的体外抗菌活性，并能有效地保护小鼠的体内菌血症。噬菌体溶素LysGH 15可能是MRSA感染的替代治疗策略。
Phage-coded lysin is an enzyme that destroys the cell walls of bacteria. Phage lysin could be an alternative to conventional antibiotic therapy against pathogens that are resistant to multiple antibiotics. In this study, a novel staphylococcal phage, GH15, was isolated, and the endogenous lytic enzyme (LysGH15) was expressed and purified. The lysin LysGH15 displayed a broad lytic spectrum; in vitro treatment killed a number of Staphylococcus aureus strains rapidly and completely, including methicillin-resistant S. aureus (MRSA). In animal experiments, a single intraperitoneal injection of LysGH15 (50 mu g) administered 1 h after MRSA injections at double the minimum lethal dose was sufficient to protect mice (P < 0.01). Bacteremia in unprotected mice reached colony counts of about 10(7) CFU/ml within 3.5 h after challenge, whereas the mean colony count in lysin-protected mice was less than 10(4) CFU/ml (and ultimately became undetectable). These results indicate that LysGH15 can kill S. aureus in vitro and can protect mice efficiently from bacteremia in vivo. The phage lysin LysGH15 might be an alternative treatment strategy for infections caused by MRSA.