Development of expanded host range phage active on biofilms of multi-drug resistant Pseudomonas aeruginosa.
Development of expanded host range phage active on biofilms of multi-drug resistant Pseudomonas aeruginosa.
复制标题
DOI：
10.1080/21597081.2015.1096995
复制
发表时间：
2016-01-01
期刊：
影响因子：
--
通讯作者：
Ramig, Robert F
中科院分区：
文献类型：
--
作者：
Mapes, Abigail C;Trautner, Barbara W;Ramig, Robert F
噬菌体治疗是对多药抗性（MDR）细菌感染的承诺治疗，但受到噬菌体的狭窄范围，我们开发了一种宿主范围扩展（HRE）协议，该方案可以扩展pseudomonas aeruginosa aeruginosa aeruginosa aeruginosa aeruginosa aeruginosa aeruginosa aeruginosa aeruginosa aeruginosa aeruginosa aeruginosa aeruginosa aeruginosa aeruginosa aeruginosa aeruginosa aeruginosa a phage。 inosa菌株开发产生了不确定的噬菌体混合物。噬菌体HRE（4xC30）表现出剂量依赖性的能力，可以通过3p。Aeruginosa临床分离物进行生物膜形成，并减少生物膜的生物膜，从而产生了高量的生物膜。 ACIN）在铜绿假单胞菌的菌株中，对左氧氟沙星有抗性。 HRE协议建立了一种快速的方法，可以创建具有庞大的宿主范围，定义成分和抗生物膜活动的噬菌体克隆和噬菌体鸡尾酒的库。
Phage therapy is a promising treatment of multi-drug resistant (MDR) bacterial infections but is limited by the narrow host range of phage. To overcome this limitation, we developed a host range expansion (HRE) protocol that expands the host range of Pseudomonas aeruginosa-specific phage by cycles of co-incubation of phage with multiple P. aeruginosa strains. Application of the HRE protocol to a mixture of 4 phages, using 16 P. aeruginosa strains for development, resulted in undefined phage mixtures with greatly expanded host range. Individual phage clones derived from the undefined mixture had expanded host ranges but no individual clone could lyse all of the strains covered by the undefined mixture from which it was isolated. Reconstituting host range-characterized clones into cocktails produced defined cocktails with predictable and broad host ranges. The undefined mixture from the 30th cycle of the mixed-phage HRE (4ϕC30) showed a dose-dependent ability to prevent biofilm formation by, and to reduce a pre-existing biofilm of, 3 P. aeruginosa clinical isolates that produced high amounts of biofilm. A defined cocktail reconstituted from 3 host range-characterized clones had activity on high biofilm-formers susceptible to the phage. Phage therapy was superior to antibiotic therapy (levofloxacin) in a strain of P. aeruginosa that was resistant to levofloxacin. The HRE protocol establishes a rapid approach to create libraries of phage clones and phage cocktails with broad host range, defined composition and anti-biofilm activity.