在小鼠感染模型中,K5 特异性噬菌体和解聚酶对肺炎克雷伯氏菌的治疗效果。

IF 3.7 1区 农林科学 Q1 VETERINARY SCIENCES
Pei Li, Genglin Guo, Xiangkuan Zheng, Sixiang Xu, Yu Zhou, Xiayan Qin, Zimeng Hu, Yanfei Yu, Zhongming Tan, Jiale Ma, Long Chen, Wei Zhang
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引用次数: 0

摘要

肺炎克雷伯菌因其严重的抗生素耐药性,已成为感染人类和动物的最棘手的革兰氏阴性病原体之一。作为抗生素的潜在替代品,噬菌体及其衍生蛋白产品正受到越来越多的关注。在这项研究中,我们分离并研究了一种新型溶菌噬菌体 P1011 的特性,它能在 26 种血清型中特异性地裂解 K5 型肺炎双球菌。我们鉴定并表达了 K5 特异性荚膜多糖降解酶 Dep1011。通过使用牛菌株 B16(能支持噬菌体增殖)和人菌株 KP181(不能维持噬菌体扩增)建立小鼠感染模型,我们探索了噬菌体和 dep1011 治疗 K5 K. pneumoniae 的安全性和有效性。噬菌体 P1011 可使接受肺炎克氏菌挑战并支持噬菌体繁殖的小鼠存活率达到 60%,同时降低小鼠血液、肝脏和肺部的细菌负荷。令人意想不到的是,即使面对噬菌体无法繁殖的细菌,噬菌体疗法也能显著减少存活生物的数量。解聚酶的保护效力明显优于噬菌体。无论噬菌体繁殖的兼容性如何,解聚酶在两个治疗组中的存活率都达到了 100%。这些发现表明,P1011和dep1011可作为潜在的抗菌剂用于控制K5肺炎克氏菌感染。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Therapeutic efficacy of a K5-specific phage and depolymerase against Klebsiella pneumoniae in a mouse model of infection.

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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来源期刊
Veterinary Research
Veterinary Research 农林科学-兽医学
CiteScore
7.00
自引率
4.50%
发文量
92
审稿时长
3 months
期刊介绍: Veterinary Research is an open access journal that publishes high quality and novel research and review articles focusing on all aspects of infectious diseases and host-pathogen interaction in animals.
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