应用噬菌体GH15和K治疗金黄色葡萄球菌感染

Combination utility of phages GH15 and K against Staphylococcus aureus

摘要:

摘要:【目的】研究金黄色葡萄球菌噬菌体GH15和K的生物学特性及联合用于治疗金黄色葡萄球菌感染的潜力。【方法】通过透射电镜观察噬菌体GH15和K的形态;测定二者的裂解谱和一步生长曲线;通过体外裂解实验和体内治疗实验分别测定单独使用GH15、K及二者混合使用时的裂解能力和对菌血症小鼠的保护效果。【结果】通过电镜观察发现两个噬菌体的外形相似，但GH15的尾部比K的长。GH15裂解谱较宽，可以裂解28株金葡菌，而K仅能裂解7株金葡菌。通过对两株噬菌体感染7株共同宿主菌形成的一步生长曲线进行拟合曲线分析，表明二者对不同宿主菌的增殖趋势是不同的。在体外，混合噬菌体与单个噬菌体的抑菌活性无明显差别;在体内实验中，混合噬菌体表现出优于单个噬菌体的治疗效果，用较低的剂量即可以达到高剂量单个噬菌体的治疗效果。【结论】GH15 和K 所形成的混合噬菌体在治疗金黄色葡萄球菌感染具有更大的应用潜力。

关键词:关键词:噬菌体，多重耐药金黄色葡萄球菌，鸡尾酒疗法

Abstract:

Abstract:［Objective］In the present report，we compared the biological characteristic of staphylococci phage GH15 and K． We also determined the therapeutic potential of the combination utility of two phages．［Methods］ The patterns of GH15 and K were detected using transmission electron microscopy．We also detected the host range and the one-step curve of phage GH15 and K．The lytic ability of mono-phage and phage cocktail was compared in vitro．Finally，the treatment effect of mono-phage and phage cocktail aginst lethal methicillin-resistant Staphylococcus aureus (MRSA) infection in mice was detected．［Results］ The length of GH15 tail was longer than that of K either in the state of contraction or noncontraction．GH15 had broader host range than K whereas both possess 7 common host strains．Although the phage cocktail had equivalent bactericidal capacity with mono-phage to most common host strains，the phage cocktail manifested more effective protection against lethal W4661 infection in mice than any mono-phage． A single smaller dose injection of phage cocktail was sufficient to protect mice effectively from fatal infection．［Conclusion］ Our results provide strong evidence towards the therapeutic use of phage cocktail as an alternative to antibiotics for acute infection caused by multidrug resistant Staphylococcus aureus．

Key words:Keywords: phage therapy，multi-drug resistant Staphylococcus aureus，cocktail