College of Veterinary Medicine, Nanjing Agricultural University, Key Lab of Animal Bacteriology, Ministry of Agriculture and Rural Affairs, Nanjing, 210095, China.
Department of Clinical Laboratory, Zhangjiagang Hospital Affiliated to Soochow University, Zhangjiagang, 215600, China.
Virol Sin. 2024 Oct;39(5):767-781. doi: 10.1016/j.virs.2024.08.002. Epub 2024 Aug 3.
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.
鲍曼不动杆菌（A.baumannii）由于其臭名昭著的抗药性，尤其是耐碳青霉烯类鲍曼不动杆菌（CRAB），对公共卫生构成了严重挑战。在这项研究中，我们从医疗废水中分离出一种烈性噬菌体，命名为 P1068，它能够裂解 CRAB，主要针对 K3 荚膜型。基本特征表明，P1068 以最佳 MOI（感染复数）1 感染 A.baumannii ZWAb014，潜伏期为 10 分钟，在 4-37°C 和 pH 值 3-10 的温度范围内保持稳定。系统发育和平均核苷酸同一性分析表明，P1068 可根据病毒分类国际委员会（ICTV）发布的最新病毒分类，归类为长尾病毒科的 Obolenskvirus 属的新型种。此外，根据经典形态分类，P1068 被鉴定为 T4 样噬菌体（肌尾病毒科）。有趣的是，我们发现 P1068 的尾丝蛋白（TFP）与 T7 样噬菌体（微尾病毒科）AbKT21phiIII（NC_048142.1）的 TFP 有 74%的覆盖度和 88.99%的同一性。这一发现表明噬菌体的 TFP 基因可能在不同的属和形态之间发生水平转移。体外抗菌试验表明，P1068 对生物膜和浮游状态下的鲍曼不动杆菌均具有抗菌活性。在腹腔感染的小鼠模型中，与对照组相比，P1068 噬菌体保护小鼠免受鲍曼不动杆菌感染，并显著降低了大脑、血液、肺、脾和肝等各种组织中的细菌负荷。综上所述，本研究表明噬菌体 P1068 可能是治疗耐碳青霉烯类和生物膜形成的鲍曼不动杆菌感染的潜在候选药物，并扩展了对噬菌体 TFP 基因水平转移的认识。
