Abstract：
Acinetobacter baumannii (A. baumannii) poses a serious public health challenge due to its notorious antimicrobial resistance, particularly carbapenem-resistant A. baumannii (CRAB). In this study, we isolated a virulent phage, named P1068, from medical wastewater capable of lysing CRAB, primarily targeting the K3 capsule type. Basic characterization showed that P1068 infected the A. baumannii ZWAb014 with an optimal MOI of 1, experienced a latent period of 10 min and maintained stability over a temperature range of 4-37 °C and pH range of 3-10. Phylogenetic and average nucleotide identity analyses indicate that P1068 can be classified as a novel species within the genus Obolenskvirus of the Caudoviricetes class as per the most recent virus classification released by the International Committee on Taxonomy of Viruses (ICTV). Additionally, according to classical morphological classification, P1068 is identified as a T4-like phage (Myoviridae). Interestingly, we found that the tail fiber protein (TFP) of P1068 shares 74% coverage and 88.99% identity with the TFP of a T7-like phage (Podoviridae), AbKT21phiIII (NC_048142.1). This finding suggests that the TFP gene of phages may undergo horizontal transfer across different genera and morphologies. In vitro antimicrobial assays showed that P1068 exhibited antimicrobial activity against A. baumannii in both biofilm and planktonic states. In mouse models of intraperitoneal infection, P1068 phage protected mice from A. baumannii infection and significantly reduced bacterial loads in various tissues such as the brain, blood, lung, spleen, and liver compared to controls. In conclusion, this study demonstrates that phage P1068 might be a potential candidate for the treatment of carbapenem-resistant and biofilm-forming A. baumannii infections, and expands the understanding of horizontal transfer of phage TFP genes.
摘要：
鲍曼不动杆菌（A.鲍曼不动）由于其臭名昭著的抗菌素耐药性而构成了严重的公共卫生挑战，特别是耐碳青霉烯的鲍曼不动杆菌(CRAB)。在这项研究中,我们分离出了一个有毒的噬菌体,命名为P1068，来自能够裂解CRAB的医疗废水，主要针对K3胶囊类型。基本表征显示,P1068以1的最佳MOI感染鲍曼不动杆菌ZWAb014,经历了十分钟的潜伏期,并且在4°C至37°C的温度范围和3-10的pH范围内保持稳定。系统发育和平均核苷酸同一性分析表明，根据国际病毒分类学委员会（ICTV）发布的最新病毒分类，P1068可被归类为Caudoviricetes类的Obolenskviricetes属中的新物种。此外,根据经典的形态学分类，P1068被鉴定为T4样噬菌体(Myoviridae)。有趣的是,我们发现P1068的尾纤维蛋白（TFP）与T7样噬菌体（Podovirridae）的TFP具有74％的覆盖率和88.99％的同一性，AbKT21phiIII(NC_048142.1)。这一发现表明噬菌体的TFP基因可能经历不同属和形态的水平转移。体外抗微生物试验表明，P1068在生物膜和浮游状态下都表现出对鲍曼不动杆菌的抗微生物活性。在腹腔感染的小鼠模型中,P1068噬菌体保护小鼠免受鲍曼不动杆菌感染，并显着降低各种组织如脑中的细菌负荷，血,肺，脾,脾和肝脏与对照组相比。总之,这项研究表明，噬菌体P1068可能是治疗耐碳青霉烯和生物膜形成鲍曼不动杆菌感染的潜在候选者，扩大了对噬菌体TFP基因水平转移的认识。
