Department of Biology, Viral Information Institute, San Diego State University, San Diego, CA 92182, USA.
Marine Microbiomes Lab, Red Sea Research Center, King Abdullah University of Science and Technology, Building 2, Level 3, Room 3216 WS03, Thuwal 23955-6900, Saudi Arabia.
Viruses. 2023 Jul 30;15(8):1665. doi: 10.3390/v15081665.
species colonization of Cystic Fibrosis respiratory airways is an increasing concern. Two adult patients with Cystic Fibrosis colonized by CF418 or CF116 experienced fatal exacerbations. spp. are naturally resistant to several antibiotics. Therefore, phages could be valuable as therapeutics for the control of . In this study, thirteen lytic phages were isolated and characterized at the morphological and genomic levels for potential future use in phage therapy. They are presented here as the Kumeyaay phage collection. Six distinct phage genome clusters were identified based on a comprehensive phylogenetic analysis of the Kumeyaay collection as well as the publicly available phages. The infectivity of all phages in the Kumeyaay collection was tested in 23 clinical isolates; 78% of these isolates were lysed by at least one phage. A cryptic prophage was induced in CF418 when infected with some of the lytic phages. This prophage genome was characterized and is presented as phage CF418-P1. Prophage induction during lytic phage preparation for therapy interventions require further exploration. Large-scale production of phages and removal of endotoxins using an octanol-based procedure resulted in a phage concentrate of 1 × 10 plaque-forming units per milliliter with an endotoxin concentration of 65 endotoxin units per milliliter, which is below the Food and Drugs Administration recommended maximum threshold for human administration. This study provides a comprehensive framework for the isolation, bioinformatic characterization, and safe production of phages to kill spp. in order to potentially manage Cystic Fibrosis (CF) pulmonary infections.
囊性纤维化呼吸道物种定殖日益受到关注。两名成年囊性纤维化患者被 CF418 或 CF116 定植，经历了致命的恶化。 spp. 天然对几种抗生素具有抗性。因此，噬菌体可能作为控制的治疗方法具有重要价值。在这项研究中，分离并表征了 13 种溶菌噬菌体，从形态和基因组水平上为未来在噬菌体治疗中的潜在应用提供了依据。它们被呈现为 Kumeyaay 噬菌体集。基于 Kumeyaay 集以及公开可用的噬菌体的综合系统发育分析，确定了六个不同的噬菌体基因组簇。在 23 个临床分离株中测试了 Kumeyaay 集所有噬菌体的感染力；其中 78%的分离株至少被一种噬菌体裂解。当用一些溶菌噬菌体感染 CF418 时，诱导了一个潜伏性原噬菌体。该原噬菌体基因组被表征，并呈现为噬菌体 CF418-P1。在治疗干预中使用溶菌噬菌体制备过程中诱导原噬菌体需要进一步探索。使用基于辛醇的程序大规模生产噬菌体并去除内毒素，导致噬菌体浓缩物的每毫升中有 1×10 个噬菌斑形成单位，内毒素浓度为每毫升 65 个内毒素单位，低于食品和药物管理局推荐的人类给药最大阈值。这项研究为分离、生物信息学表征和安全生产噬菌体提供了一个全面的框架，以杀死 spp.，从而有可能管理囊性纤维化（CF）肺部感染。
