Shi Lingrui, Su Yuanhui, Li Zhen, Xiang Li, Liu Siyuan, Li Xingming, Fu Li, Zhou Yingshun
Department of Pathogenic Biology, School of Basic Medicine, Southwest Medical University, No. 1 Section 1, Xiang Lin Road, Longmatan District, Luzhou, 646000, Sichuan, China.
Department of Reproductive Medicine, The Affiliated Hospital, Southwest Medical University, No. 25 Tai Ping Road, Jiangyang District Luzhou, Sichuan, 646000, China.
Probiotics Antimicrob Proteins. 2025 Jun 25. doi: 10.1007/s12602-025-10633-z.
In order to address the issue of antimicrobial resistance posed by hypervirulent Klebsiella pneumoniae (hvKp), bacteriophages that selectively target and lyse the bacteria are being investigated as a promising therapeutic option for the treatment of clinical infections associated with hvKp. The phage vB_LZ 2044, which was isolated and characterized utilizing hvKp NTUH-K2044 as the host strain, demonstrates significant efficacy against nine distinct K1 serotype Klebsiella pneumoniae strains and exhibits an impressive lysing capacity of 396.7 PFU/cell at burst size. Moreover, it displays remarkable stability across a wide pH range (pH 4-10) and temperature range (4-40 °C), positioning it as a promising antimicrobial agent. Genetic analysis has revealed that vB_LZ 2044 is a 50419 bp double-stranded DNA phage classified under the genus Webervirus within the family Drexlerviridae. The putative Open Reading Frames (ORFs) encoded by the phage, including the perforin-endolysin-spanin system protein (ORF26, ORF27, ORF28) and the peptin lyase folds containing the tailspike protein (ORF10), are crucial for lysing the host bacteria. Furthermore, experiments conducted on mice have demonstrated the effectiveness of vB_LZ 2044 in treating hvKp-induced liver infections without inflicting additional damage to the liver tissues, thus preserving the integrity of the liver structure and mitigating inflammation. The stable biological properties and pronounced antimicrobial effects observed in the mice model suggest that phage vB_LZ 2044 holds significant potential for development as a novel antimicrobial agent.
为了解决高毒力肺炎克雷伯菌（hvKp）引起的抗菌药物耐药性问题，正在研究能够选择性靶向并裂解该细菌的噬菌体，将其作为治疗与hvKp相关临床感染的一种有前景的治疗选择。以hvKp NTUH-K2044作为宿主菌株分离并鉴定的噬菌体vB_LZ 2044，对9种不同的K1血清型肺炎克雷伯菌菌株显示出显著疗效，并且在爆发量时表现出令人印象深刻的396.7 PFU/细胞的裂解能力。此外，它在较宽的pH范围（pH 4-10）和温度范围（4-40°C）内都表现出显著的稳定性，使其成为一种有前景的抗菌剂。基因分析表明，vB_LZ 2044是一种50419 bp的双链DNA噬菌体，归类于德雷克斯勒病毒科的韦伯病毒属。该噬菌体编码的推定开放阅读框（ORF），包括穿孔素-内溶素-跨度蛋白系统蛋白（ORF26、ORF27、ORF28）和含有尾刺蛋白的肽溶酶折叠（ORF10），对于裂解宿主细菌至关重要。此外，在小鼠身上进行的实验证明了vB_LZ 2044在治疗hvKp诱导的肝脏感染方面的有效性，且不会对肝脏组织造成额外损伤，从而保持肝脏结构的完整性并减轻炎症。在小鼠模型中观察到的稳定生物学特性和显著抗菌效果表明，噬菌体vB_LZ 2044作为一种新型抗菌剂具有巨大的开发潜力。
