Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, Republic of Korea.
Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, Republic of Korea
Appl Environ Microbiol. 2019 Apr 18;85(9). doi: 10.1128/AEM.02900-18. Print 2019 May 1.
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.
广泛耐药的 （XDR-PA） 是一种危及生命的病原体，它导致了严重的全球性问题。在这里，我们研究了两种新型噬菌体 （phages），Bϕ-R656 和 Bϕ-R1836 ，以评估噬菌体治疗控制 XDR-PA 临床菌株的潜力。Bϕ-R656 和 Bϕ-R1836 属于 家族，表现出广泛的宿主范围，可以裂解 28 株 XDR-PA 菌株中的 18 株（64%）和 14 株（50%）。此外，这两种噬菌体对来自肺炎患者的 XDR-PA 宿主菌株表现出强烈的溶菌活性。Bϕ-R656 和 Bϕ-R1836 的全基因组分别为 60919 和 37714 bp 的线性双链 DNA。Bϕ-R656 的完整序列与 GenBank 中先前发现的噬菌体相似度非常低，但噬菌体 Bϕ-R1836 与噬菌体 YMC12/01/R24 和 PA1/KOR/2010 的核苷酸相似度分别为 98%和 91%。在两种 感染模型中，与未治疗的对照组相比，噬菌体 Bϕ-R656 和 Bϕ-R1836 处理可分别在感染后 72 小时提高幼虫（50%和 60%）的存活率和感染后 12 天肺炎模型小鼠（66%和 83%）的存活率。噬菌体 Bϕ-R656 或 Bϕ-R1836 处理还显著降低了肺炎模型小鼠肺部的细菌负荷（分别减少>6 对数 CFU 和>4 对数 CFU），第 5 天。在这项研究中，我们评估了两种新型 噬菌体 Bϕ-R656 和 Bϕ-R1836 作为治疗肺炎患者分离的 XDR-PA 菌株的替代抗菌药物的治疗效果和安全性。两种噬菌体均表现出强大的溶菌活性，并大大提高了幼虫感染和小鼠急性肺炎模型的存活率。基于这些结果，我们强烈预测这两种新噬菌体可以作为针对 XDR-PA 感染的快速作用和安全的替代生物武器。
