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
作者： Li, Pei 1 ; Guo, Genglin 3 ; Zheng, Xiangkuan 1 ; Xu, Sixiang 1 ; Zhou, Yu 1 ; Qin, Xiayan 1 ; Hu, Zimeng 1 ; Yu, Yanfei 4 ; Tan, Zhongming 5 ; Ma, Jiale 1 ; Chen, Long 6 ; Zhang, Wei 1 ;
作者机构： 1.Nanjing Agr Univ, Coll Vet Med, MOE Joint Int Res Lab Anim Hlth & Food Safety, Key Lab Anim Bacteriol,Minist Agr, Nanjing 210095, Peoples R China
2.Nanjing Agr Univ, Sanya Inst, Yabulun Ind Pk, Sanya 572024, Peoples R China
3.Shandong Acad Agr Sci, Shandong Inst Sericulture, Yantai, Peoples R China
4.Jiangsu Acad Agr Sci, Minist Agr & Rural Affairs, Inst Vet Med, Key Lab Vet Biol Engn & Technol, Nanjing, Peoples R China
5.Jiangsu Prov Ctr Dis Control & Prevent, NHC Key Lab Enter Pathogen Microbiol, Nanjing 210014, Peoples R China
6.Soochow Univ, Zhangjiagang Hosp, Dept Clin Lab, Zhangjiagang 215600, Peoples R China
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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