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Development of expanded host range phage active on biofilms of multi-drugresistant Pseudomonas aeruginosa

机译：发展扩大宿主范围噬菌体活跃生物膜的multi-drugresistant假单胞菌绿脓杆菌

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Phage therapy is a promising treatment of multi-drug resistant (MDR) bacterial infections but islimited by the narrow host range of phage. To overcome this limitation, we developed a host rangeexpansion (HRE) protocol that expands the host range of Pseudomonas aeruginosa-specific phage bycycles of co-incubation of phage with multiple P. aeruginosa strains. Application of the HRE protocolto a mixture of 4 phages, using 16 P. aeruginosa strains for development, resulted in undefined phagemixtures with greatly expanded host range. Individual phage clones derived from the undefinedmixture had expanded host ranges but no individual clone could lyse all of the strains covered by theundefined mixture from which it was isolated. Reconstituting host range-characterized clones intococktails produced defined cocktails with predictable and broad host ranges. The undefined mixturefrom the 30th cycle of the mixed-phage HRE (4fC30) showed a dose-dependent ability to preventbiofilm formation by, and to reduce a pre-existing biofilm of, 3 P. aeruginosa clinical isolates thatproduced high amounts of biofilm. A defined cocktail reconstituted from 3 host range-characterizedclones had activity on high biofilm-formers susceptible to the phage. Phage therapy was superior toantibiotic therapy (levofloxacin) in a strain of P. aeruginosa that was resistant to levofloxacin. The HREprotocol establishes a rapid approach to create libraries of phage clones and phage cocktails withbroad host range, defined composition and anti-biofilm activity.
机译：噬菌体疗法是一种有前途的治疗方法耐多药(MDR)的细菌感染但由狭隘的噬菌体的宿主范围有限。为了克服这个限制,我们开发了一个主机rangeexpansion(一定是)协议扩展了假单胞菌的宿主范围aeruginosa-specific噬菌体bycycles co-incubation的噬菌体多个铜绿假单胞菌菌株。protocolto一定是4噬菌体的混合物,使用16个发展铜绿假单胞菌菌株,导致未定义phagemixtures大大宿主范围扩大。来自undefinedmixture已经扩大宿主范围但没有个体克隆可以溶解所有的菌株被theundefined覆盖混合物被孤立。重组宿主range-characterized克隆intococktails生产定义的鸡尾酒可预见的和广泛的宿主范围。mixturefrom的30日周期mixed-phage一定是(4 fc30)显示能力存在剂量依赖的相关性preventbiofilm形成,减少一个预先存在的生物膜,3铜绿假单胞菌临床隔离thatproduced大量的生物膜。定义鸡尾酒重组从3主机range-characterizedclones有活动biofilm-formers容易噬菌体。治疗是上级toantibiotic治疗(左氧氟沙星)株铜绿假单胞菌是左氧氟沙星耐药。建立一个快速的方法来创建库噬菌体克隆和噬菌体的鸡尾酒withbroad宿主范围、组成和anti-biofilm定义活动。

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