Therapeutic efficacy of a K5-specific phage and depolymerase against Klebsiella pneumoniae in a mouse model of infection

文献类型： 外文期刊

第一作者： Li, Pei

作者： Li, Pei;Zheng, Xiangkuan;Xu, Sixiang;Zhou, Yu;Qin, Xiayan;Hu, Zimeng;Ma, Jiale;Zhang, Wei;Li, Pei;Zheng, Xiangkuan;Xu, Sixiang;Zhou, Yu;Hu, Zimeng;Zhang, Wei;Guo, Genglin;Yu, Yanfei;Tan, Zhongming;Chen, Long

作者机构：

关键词： Klebsiella pneumoniae; phage; depolymerase; K5; hypervirulent; capsule

期刊名称：VETERINARY RESEARCH （ 影响因子：4.4； 五年影响因子：4.3 ）

ISSN： 0928-4249

年卷期： 2024 年 55 卷 1 期

页码：

收录情况： SCI

摘要： Klebsiella pneumoniae has become one of the most intractable gram-negative pathogens infecting humans and animals due to its severe antibiotic resistance. Bacteriophages and protein products derived from them are receiving increasing amounts of attention as potential alternatives to antibiotics. In this study, we isolated and investigated the characteristics of a new lytic phage, P1011, which lyses K5 K. pneumoniae specifically among 26 serotypes. The K5-specific capsular polysaccharide-degrading depolymerase dep1011 was identified and expressed. By establishing murine infection models using bovine strain B16 (capable of supporting phage proliferation) and human strain KP181 (incapable of sustaining phage expansion), we explored the safety and efficacy of phage and dep1011 treatments against K5 K. pneumoniae. Phage P1011 resulted in a 60% survival rate of the mice challenged with K. pneumoniae supporting phage multiplication, concurrently lowering the bacterial burden in their blood, liver, and lungs. Unexpectedly, even when confronted with bacteria impervious to phage multiplication, phage therapy markedly decreased the number of viable organisms. The protective efficacy of the depolymerase was significantly better than that of the phage. The depolymerase achieved 100% survival in both treatment groups regardless of phage propagation compatibility. These findings indicated that P1011 and dep1011 might be used as potential antibacterial agents to control K5 K. pneumoniae infection.

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