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

被引:171
作者
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
机构
[1] Kochi Med Sch Hosp, Kochi Med Sch, Dept Biochem, Kochi, Japan
[2] Kochi Med Sch Hosp, Kochi Med Sch, Dept Microbiol & Infect, Kochi, Japan
[3] Kochi Med Sch Hosp, Kochi Med Sch, Dept Pediat, Kochi, Japan
[4] Kochi Med Sch Hosp, Kochi Med Sch, Dept Gen Med, Kochi, Japan
[5] Kochi Med Sch Hosp, Kochi Med Sch, Clin Lab Ctr, Kochi, Japan
[6] Kochi Univ, Ctr Sci Res, Sect Life Sci & Biofunct Mat, Nankoku, Kochi, Japan
[7] Kochi Gakuen Jr Coll, Kochi, Japan
[8] Hiroshima Univ, Grad Sch Biomed Sci, Dept Bacteriol, Hiroshima, Japan
[9] Juntendo Univ, Dept Bacteriol, Tokyo, Japan
基金
日本科学技术振兴机构;
关键词
D O I
10.1086/521305
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:1237 / 1247
页数:11
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