Li Qiming, Li Jiaqi, Zhao Yanyang, Guo Shuai, Liu Mengzhe, Shi Xiaoyu, Wang Li, Liu Zhigang, Teng Tieshan
Henan Province EngineeringTechnology Research Center of Rapid-Accuracy Medical Diagnostics, Department of Clinical Laboratory, The First Affiliated Hospital of Henan University, Henan University, Kaifeng, 475000, China.
The Jointed National Laboratory of Antibody Drug Engineering, Henan University, Kaifeng, 475000, China.
AMB Express. 2025 Jul 30;15(1):112. doi: 10.1186/s13568-025-01919-0.
The emergence and spread of multidrug-resistant and super-resistant bacterial strains have positioned phage therapy as a highly promising approach for future infection treatments. Klebsiella pneumoniae, a leading cause of clinical infections and hospital-acquired diseases, is responsible for over 95% of infections within the Klebsiella genus. Phages targeting K. pneumoniae exhibit remarkable diversity, with numerous isolates identified against various serotypes of this pathogen. In this study, we described the isolation and characterization of a novel bacteriophage from hospital sewage, Henu2_3, which targeted clinical isolates of K1-type K. pneumoniae. Transmission electron microscopy revealed that phage Henu2_3 possessed an icosahedral head and podovirus morphotype. The phage genome comprises 42,878 base pairs with a G + C content of 53.97%, encoding 54 putative open reading frames. One-step growth curve analysis demonstrated that phage Henu2_3 has a latency period of 10 min and an average burst size of 215 phage particles per infected cell. Additionally, Henu2_3 exhibited remarkable stability, tolerating temperatures up to 60℃ and maintaining maximum viability across a broad pH range of 4 to 12. In vivo infection models demonstrated that phage Henu2_3 markedly enhanced animal survival and decreased bacterial burden in target organs. These properties highlight its potential as a therapeutic agent against K. pneumoniae infections.
多重耐药和超级耐药细菌菌株的出现与传播，使噬菌体疗法成为未来感染治疗中极具前景的方法。肺炎克雷伯菌是临床感染和医院获得性疾病的主要病因，在克雷伯菌属感染中占比超过95%。针对肺炎克雷伯菌的噬菌体表现出显著的多样性，已鉴定出许多针对该病原体不同血清型的分离株。在本研究中，我们描述了从医院污水中分离并鉴定出一种新型噬菌体Henu2_3，它靶向K1型肺炎克雷伯菌的临床分离株。透射电子显微镜显示，噬菌体Henu2_3具有二十面体头部和足状病毒形态型。噬菌体基因组由42,878个碱基对组成，G + C含量为53.97%，编码54个推定的开放阅读框。一步生长曲线分析表明，噬菌体Henu2_3的潜伏期为10分钟，每个感染细胞的平均裂解量为215个噬菌体颗粒。此外，Henu2_3表现出显著的稳定性，能耐受高达60℃的温度，并在4至12的广泛pH范围内保持最大活力。体内感染模型表明，噬菌体Henu2_3显著提高了动物存活率，并降低了靶器官中的细菌载量。这些特性突出了其作为抗肺炎克雷伯菌感染治疗剂的潜力。
