a method for generation phage cocktail with great therapeutic potential方法一代噬菌体鸡尾酒的治疗潜力.pdfVIP

a method for generation phage cocktail with great therapeutic potential方法一代噬菌体鸡尾酒的治疗潜力.pdf

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a method for generation phage cocktail with great therapeutic potential方法一代噬菌体鸡尾酒的治疗潜力

A Method for Generation Phage Cocktail with Great Therapeutic Potential Jingmin Gu, Xiaohe Liu, Yue Li, Wenyu Han*, Liancheng Lei, Yongjun Yang, Honglei Zhao, Yu Gao, Jun Song, Rong Lu, Changjiang Sun, Xin Feng College of Animal Science and Veterinary Medicine, Jilin University, Changchun, People’s Republic of China Abstract Background: Bacteriophage could be an alternative to conventional antibiotic therapy against multidrug-resistant bacteria. However, the emergence of resistant variants after phage treatment limited its therapeutic application. Methodology/Principal Findings: In this study, an approach, named ‘‘Step-by-Step’’ (SBS), has been established. This method takes advantage of the occurrence of phage-resistant bacteria variants and ensures that phages lytic for wild-type strain and its phage-resistant variants are selected. A phage cocktail lytic for Klebsiella pneumoniae was established by the SBS method. This phage cocktail consisted of three phages (GH-K1, GH-K2 and GH-K3) which have different but overlapping host strains. Several phage-resistant variants of Klebsiella pneumoniae were isolated after different phages treatments. The virulence of these variants was much weaker [minimal lethal doses (MLD).1.36109 cfu/mouse] than that of wild-type K7 countpart (MLD = 2.5 6103 cfu/mouse). Compared with any single phage, the phage cocktail significantly reduced the mutation frequency of Klebsiella pneumoniae and effectively rescued Klebsiella pneumoniae bacteremia in a murine K7 strain challenge model. The minimal protective dose (MPD) of the phage cocktail which was sufficient to protect bacteremic mice 4 from lethal K7 infection was only 3.0 610 pfu, significantly smaller (p,0.01) than that of single monophage. Moreover, a delayed administration of this phage cock

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