vB_PaeP_PZH3，一种用于治疗小鼠伤口感染模型中耐多药铜绿假单胞菌的新型噬菌体。

vB_PaeP_PZH3, a novel bacteriophage for the treatment of MDR Pseudomonas aeruginosa in a mouse wound infection model.

作者信息

Ma Jiucheng, Pang Xiaoxiao, Zhang Ruxia, Ding Chao, Zheng Yu, Zhao Yingfeng, Qian Like, Ni Jiamin, Ji Jiahao, Kong Xianghu, Hu Wei, Chang Fei, Chen Long

机构信息

Department of Plastic and Burns Surgery, The First People's Hospital of Zhangjiagang City, Zhangjiagang Hospital Affiliated to Soochow University, Zhangjiagang, Jiangsu, China.

Department of Clinical Laboratory, The First People's Hospital of Zhangjiagang City, Zhangjiagang Hospital Affiliated to Soochow University, Zhangjiagang, Jiangsu, China.

出版信息

J Glob Antimicrob Resist. 2025 Jun 28;44:197-206. doi: 10.1016/j.jgar.2025.06.019.

DOI:10.1016/j.jgar.2025.06.019

PMID:40588032

Abstract

OBJECTIVE

Pseudomonas aeruginosa is a major causative agent of wound infections, and the emergence of multidrug-resistant (MDR) strains complicates clinical treatment. This study evaluates the therapeutic efficacy of a novel lytic phage, vB_PaeP_PZH3, against MDR P. aeruginosa in a mouse wound infection model.

METHODS

The phage vB_PaeP_PZH3 was isolated from hospital wastewater. Temperature and pH stability, host range, optimal multiplicity of infection (MOI), one-step growth test, transmission electron microscopy, sequencing and genomic analysis were performed to analyse the characteristics of vB_PaeP_PZH3. A bacteriostatic assay was performed to evaluate the antibacterial activity in vitro. Therapeutic efficacy was observed in a mouse wound infection model.

RESULTS

Phage vB_PaeP_PZH3 is a novel short-tailed phage belonging to the genus Phikmvvirus in the family Autographiviridae. vB_PaeP_PZH3 was stable from 4°C to 50°C and pH 5-10 and produced the highest phage potency at a multiplicity of infection of 0.01. The one-step growth curve showed that the incubation period of vB_PaeP_PZH3 was 10 min, and the burst was approximately 959 PFU/infected cell. vB_PaeP_PZH3 could lyse more than half of the P. aeruginosa strains tested. The phage genome comprised 43 567 bp with 62.24% G+C content and harboured 53 coding sequences, none of which showed homology to known virulence genes, indicating its therapeutic safety. vB_PaeP_PZH3 showed strong antibacterial activity and biofilm-cleaning ability in vitro. In the mouse model, vB_PaeP_PZH3 treatment promoted the repair and healing of infected wounds.

CONCLUSIONS

Phage vB_PaeP_PZH3 shows therapeutic potential against wound infections caused by MDR P. aeruginosa.

摘要

目的

铜绿假单胞菌是伤口感染的主要致病菌，多重耐药（MDR）菌株的出现使临床治疗变得复杂。本研究在小鼠伤口感染模型中评估新型裂解性噬菌体vB_PaeP_PZH3对MDR铜绿假单胞菌的治疗效果。

方法

噬菌体vB_PaeP_PZH3从医院废水中分离得到。进行温度和pH稳定性、宿主范围、最佳感染复数（MOI）、一步生长试验、透射电子显微镜观察、测序和基因组分析以分析vB_PaeP_PZH3的特性。进行抑菌试验以评估其体外抗菌活性。在小鼠伤口感染模型中观察治疗效果。

结果

噬菌体vB_PaeP_PZH3是一种新型短尾噬菌体，属于自显病毒科的Phikmvvirus属。vB_PaeP_PZH3在4°C至50°C和pH 5 - 10范围内稳定，在感染复数为0.01时产生最高噬菌体效价。一步生长曲线显示vB_PaeP_PZH3的潜伏期为10分钟，裂解量约为959个噬菌斑形成单位/感染细胞。vB_PaeP_PZH3可裂解超过一半的测试铜绿假单胞菌菌株。噬菌体基因组由43567 bp组成，G+C含量为62.24%，包含53个编码序列，其中没有一个与已知毒力基因显示同源性，表明其治疗安全性。vB_PaeP_PZH3在体外显示出强大的抗菌活性和生物膜清除能力。在小鼠模型中，vB_PaeP_PZH3治疗促进了感染伤口的修复和愈合。