Chen Jinfeng, Feng Junxia, Cui Xiaohu, Huang Lijuan, Du Bing, Xia Yuyan, Xue Guanhua, Feng Yanling, Ke Yuehua, Zhao Hanqing, Cui Jinghua, Yan Chao, Gan Lin, Fan Zheng, Fu Tongtong, Xu Ziying, Yang Yang, Yu Zihui, Zhao Shuo, Wang Zhen, Kong Yiming, Jiang Boyi, Wang Mingxuan, Ling Mengyao, Yuan Jing
Capital Institute of Pediatrics-Peking University Teaching Hospital, Beijing, China.
Department of Bacteriology, Capital Institute of Pediatrics, Beijing, China.
mSystems. 2025 May 20;10(5):e0163224. doi: 10.1128/msystems.01632-24. Epub 2025 Apr 16.
Hypervirulent (hvKp) strains are increasingly recognized for their aggressive nature, which leads to severe clinical outcomes. The emergence of multidrug-resistant strains constitutes a substantial challenge for clinical management. Phage therapy offers a potential solution to the antibiotic resistance crisis. A multidrug-resistant hvKp strain, K2420 (K20 serotype), was used to isolate bacteriophages from hospital sewage. Phage morphology, biological properties, and genome characteristics were analyzed using transmission electron microscopy, plaque assays, and whole-genome sequencing. Therapeutic safety and efficacy were assessed in an acute pneumonia murine model induced by intratracheal injection of K2420. Assessment parameters included bacterial load, phage titer, body temperature, cytokine levels, histopathological findings, and other relevant indicators. Phage PK2420, a member of the family and genus, was identified. It rapidly lyses (K20 serotype), inhibits biofilm formation, and exhibits a burst size of 37.4 plaque-forming units/cell. The phage is stable at temperatures ranging from 0°C to 40°C and pH values between 6 and 9. Its genome, 41,155 bp in length, contains 46 coding sequences. The phage has no genes associated with antibiotic resistance, virulence, or lysogeny. , PK2420 substantially reduced bacterial loads, improved survival rates, and alleviated pneumonia severity without observable side effects. Phage PK2420 exhibits lytic activity against both and in murine models, providing a promising and safe option for the treatment of hvKp infections.IMPORTANCEOur investigation provides insights into the interaction mechanism among hypervirulent (hvKp) (K20 serotype), phage, and the host in a mouse pneumonia model, offering a valuable reference for future research on phage pharmacokinetics. This study demonstrated that bacteriophage PK2420 exhibits promising biosafety and therapeutic efficacy against hvKp-induced pulmonary infections and dissemination in a murine model. These findings suggest that phage PK2420 may be a potential option for the clinical treatment of hvKp infections.
高毒力（hvKp）菌株因其侵袭性而日益受到关注，这种侵袭性会导致严重的临床后果。多重耐药菌株的出现给临床治疗带来了巨大挑战。噬菌体疗法为抗生素耐药危机提供了一种潜在的解决方案。一株多重耐药的hvKp菌株K2420（K20血清型）被用于从医院污水中分离噬菌体。使用透射电子显微镜、噬菌斑测定和全基因组测序分析了噬菌体的形态、生物学特性和基因组特征。通过气管内注射K2420诱导的急性肺炎小鼠模型评估治疗安全性和疗效。评估参数包括细菌载量、噬菌体滴度、体温、细胞因子水平、组织病理学结果和其他相关指标。鉴定出噬菌体PK2420，它属于 科 属。它能迅速裂解 （K20血清型），抑制生物膜形成，并且裂解量为37.4噬菌斑形成单位/细胞。该噬菌体在0°C至40°C的温度范围和pH值6至9之间稳定。其基因组长度为41,155 bp，包含46个编码序列。该噬菌体没有与抗生素耐药性、毒力或溶原性相关的基因。 ，PK2420显著降低了 细菌载量，提高了存活率，并减轻了肺炎严重程度，且没有明显的副作用。噬菌体PK2420在小鼠模型中对 和 均表现出裂解活性，为治疗hvKp感染提供了一种有前景且安全的选择。重要性我们的研究深入了解了高毒力（hvKp）（K20血清型）、噬菌体和宿主在小鼠肺炎模型中的相互作用机制，为未来噬菌体药代动力学研究提供了有价值的参考。本研究表明，噬菌体PK2420在小鼠模型中对hvKp诱导的肺部感染和播散具有良好的生物安全性和治疗效果。这些发现表明，噬菌体PK2420可能是临床治疗hvKp感染的一个潜在选择。
