Efficient elimination of multidrug-resistant Staphylococcus aureus by cloned lysin derived from bacteriophage φMR11

Efficient elimination of multidrug-resistant Staphylococcus aureus by cloned lysin derived from bacteriophage φMR11
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DOI:
10.1086/521305
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发表时间:
2007-10-15
影响因子:
6.4
通讯作者:
Matsuzaki, Shigenobu
Matsuzaki, Shigenobu
中科院分区:
医学2区
文献类型:
--
作者:
Rashel, Mohammad;Uchiyama, Jumpei;Matsuzaki, Shigenobu

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我们报告了一种新的金黄色葡萄球菌噬菌体phiMR 11编码的克隆溶素的成功纯化。MV-L溶素能迅速、完全地溶解多种链球菌细胞。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)和万古霉素耐药的S.金黄色葡萄球菌和万古霉素中间体S.金黄色葡萄球菌(VISA)在生长条件下。MV-L介导的杀伤作用对S.金黄色葡萄球菌(S. aureus)对其他菌种无明显的敏感性。simulans。MV-L与糖肽类抗生素对VISA有协同作用。MV-L能有效地清除人工接种到小鼠鼻孔中的MRSA。MV-L的腹膜内施用还保护小鼠免于MRSA感染性死亡,而没有任何有害作用。尽管MV-L在小鼠中诱发了可检测水平的体液应答,但抗体并没有消除溶菌活性。这些结果表明,MV-L可能是一种有效的治疗药物,对多重耐药的S。金黄色葡萄球菌感染
We report the successful purification of a cloned lysin encoded by the novel Staphylococcus aureus bacteriophage phi MR11. The lysin, designated MV-L, rapidly and completely lysed cells of a number of S. aureus strains tested, including methicillin-resistant S. aureus (MRSA) and vancomycin-resistant S. aureus and a subset of vancomycin-intermediate S. aureus ( VISA) in growing conditions. MV-L-mediated killing is specific to S. aureus and not to other species, except for S. simulans. MV-L exerted its staphylocidal effect synergistically with glycopeptide antibiotics against VISA. MV-L efficiently eliminated MRSA that had been artificially inoculated into the nares of mice. The intraperitoneal administration of MV-L also protected mice against MRSA septic death, without any harmful effects. Although MV-L evoked detectable levels of a humoral response in mice, the antibodies did not abolish the bacteriolytic activity. These results indicate that MV-L might be useful as a powerful therapeutic agent against multidrug-resistant S. aureus infections.