Rashel Mohammad, Uchiyama Jumpei, Ujihara Takako, Uehara Yoshio, Kuramoto Shu, Sugihara Shigeyoshi, Yagyu Ken-Ichi, Muraoka Asako, Sugai Motoyuki, Hiramatsu Keiichi, Honke Koichi, Matsuzaki Shigenobu
Department of Biochemistry, Kochi Medical School, Nankoku 783-8505, Japan.
J Infect Dis. 2007 Oct 15;196(8):1237-47. doi: 10.1086/521305. Epub 2007 Sep 11.
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.
我们报告了由新型金黄色葡萄球菌噬菌体phi MR11编码的一种克隆溶素的成功纯化。这种溶素命名为MV-L,在生长条件下能快速且完全地裂解多种测试的金黄色葡萄球菌菌株的细胞,包括耐甲氧西林金黄色葡萄球菌(MRSA)、耐万古霉素金黄色葡萄球菌以及一部分万古霉素中介金黄色葡萄球菌(VISA)。MV-L介导的杀伤作用对金黄色葡萄球菌具有特异性,除了模仿葡萄球菌外,对其他物种无作用。MV-L与糖肽类抗生素对VISA发挥协同杀葡萄球菌作用。MV-L能有效清除人工接种到小鼠鼻腔内的MRSA。腹腔注射MV-L还能保护小鼠免于MRSA败血症死亡,且无任何有害影响。尽管MV-L在小鼠体内引发了可检测水平的体液反应,但这些抗体并未消除其溶菌活性。这些结果表明,MV-L可能作为一种强大的治疗剂用于对抗多重耐药金黄色葡萄球菌感染。