KP-C01: A Novel Phage with Tail-Associated Depolymerase Activity Against KL102 Carbapenem-Resistant Klebsiella pneumoniae.

IF 1.8
PHAGE (New Rochelle, N.Y.) Pub Date : 2026-01-14 eCollection Date: 2026-03-01 DOI:10.1177/26416549251406409
Lan Yang, Jie Li, Jia Dai, Jianfang Liu, Demeng Tan, Nannan Wu, Tongyu Zhu, Mengjun Cheng
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Abstract

Background: The emergence and spread of carbapenem-resistant Klebsiella pneumoniae (CRKP) represent a major threat to global public health, necessitating effective therapeutic strategies to prevent infection.

Materials and methods: A novel bacteriophage, φKP-C01, was isolated and characterized using ST307KL102 CRKP as the host.

Results: One-step growth curve analysis and complete genome sequencing demonstrated φKP-C01 to be a highly efficient lytic phage. The absence of genes encoding virulence factors, drug resistance determinants, or lysogeny-related functions indicated its potential safety for therapeutic applications. Bioinformatic analysis identified orf5 as encoding Depo-C01, a putative tail fiber protein with predicted depolymerase activity. To validate this function, orf5 was cloned, and recombinant Depo-C01 was expressed and purified. Depolymerase activity specifically targeting the KL102 capsular polysaccharide of the CRKP host was confirmed via spot assay and transmission electron microscopy.

Conclusion: Lytic phage φKP-C01 and its depolymerase Depo-C01 show strong potential for phage-based or enzymatic strategies targeting CRKP infections.

具有抗KL102耐碳青霉烯肺炎克雷伯菌尾部相关解聚合酶活性的新型噬菌体KP-C01
背景:碳青霉烯耐药肺炎克雷伯菌(CRKP)的出现和传播对全球公共卫生构成重大威胁,需要有效的治疗策略来预防感染。材料与方法:以ST307KL102 CRKP为宿主,分离并鉴定了一种新型噬菌体φKP-C01。结果:一步生长曲线分析和全基因组测序证实φKP-C01是高效的噬菌体。缺乏编码毒力因子、耐药决定因素或溶原相关功能的基因表明其治疗应用的潜在安全性。生物信息学分析发现orf5编码Depo-C01,一种推测具有解聚合酶活性的尾纤维蛋白。为了验证这一功能,我们克隆了orf5,表达并纯化了重组Depo-C01。通过斑点实验和透射电镜证实了特异性靶向CRKP宿主KL102荚膜多糖的解聚合酶活性。结论:噬菌体φKP-C01及其解聚合酶Depo-C01具有很强的潜力,可用于噬菌体或酶制剂靶向CRKP感染。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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