Two Novel Bacteriophages Improve Survival in Infection and Mouse Acute Pneumonia Models Infected with Extensively Drug-Resistant .

Extensively drug-resistant (XDR-PA) is a life-threatening pathogen that causes serious global problems. Here, we investigated two novel bacteriophages (phages), Bϕ-R656 and Bϕ-R1836, , , and to evaluate the potential of phage therapy to control XDR-PA clinical strains. Bϕ-R656 and Bϕ-R1836 belong to the family and exhibited broad host ranges which could lyse 18 (64%) and 14 (50%) of the 28 XDR-PA strains. In addition, the two phages showed strong bacteriolytic activity against XDR-PA host strains from pneumonia patients. The whole genomes of Bϕ-R656 and Bϕ-R1836 have linear double-stranded DNA of 60,919 and 37,714 bp, respectively. The complete sequence of Bϕ-R656 had very low similarity to the previously discovered phages in GenBank, but phage Bϕ-R1836 exhibited 98% and 91% nucleotide similarity to phages YMC12/01/R24 and PA1/KOR/2010, respectively. In the two infection models, treatment with Bϕ-R656 and Bϕ-R1836 enhanced the survival of larvae (50% and 60%, respectively) at 72 h postinfection and pneumonia-model mice (66% and 83%, respectively) at 12 days postinfection compared with untreated controls. Treatment with Bϕ-R656 or Bϕ-R1836 also significantly decreased the bacterial load in the lungs of the mouse pneumonia model (>6 log CFU and >4 log CFU, respectively) on day 5. In this study, two novel phages, Bϕ-R656 and Bϕ-R1836, were evaluated , , and for therapeutic efficacy and safety as an alternative antibacterial agent to control XDR-PA strains collected from pneumonia patients. Both phages exhibited potent bacteriolytic activity and greatly improved survival in larva infection and a mouse acute pneumonia model. Based on these results, we strongly predict that these two new phages could be used as fast-acting and safe alternative biological weapons against XDR-PA infections.