Phage Selective Pressure Reduces Virulence of Hypervirulent Klebsiella pneumoniae Through Mutation of the wzc Gene.
Phage Selective Pressure Reduces Virulence of Hypervirulent Klebsiella pneumoniae Through Mutation of the wzc Gene.
复制标题
噬菌体选择压力通过 wzc 基因突变降低高毒力肺炎克雷伯菌的毒力
DOI：
10.3389/fmicb.2021.739319
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发表时间：
2021
影响因子：
5.2
通讯作者：
Jia X
中科院分区：
文献类型：
--
作者：
Song L;Yang X;Huang J;Zhu X;Han G;Wan Y;Xu Y;Luan G;Jia X
超强毒力肺炎克雷伯菌(HvKp)是社区获得性肺炎的主要病原体之一，可引起肝脓肿等侵袭性感染。近年来，噬菌体已被用于肺炎克雷伯菌的治疗，但在噬菌体治疗过程中产生的抗噬菌体的特性有待评估。本研究分离并鉴定了两个Podoviridae噬菌体hvKpP1和hvKpP2。体外和体内实验表明，与野生型相比，抗性细菌的毒力明显降低。克隆测序的比较基因组分析表明，wzc和wcaJ基因的核苷酸缺失突变导致了噬菌体抗性，而电子显微镜和粘液黏度结果表明突变导致了囊膜的丢失。同时，动物实验表明，包膜的丧失降低了hvKp的毒力。这些发现有助于更好地理解噬菌体疗法，该疗法不仅可以直接杀灭细菌，还可以通过噬菌体筛选来降低细菌的毒力。
Hypervirulent Klebsiella pneumoniae (hvKp), one of the major community-acquired pathogens, can cause invasive infections such as liver abscess. In recent years, bacteriophages have been used in the treatment of K. pneumoniae, but the characteristics of the phage-resistant bacteria produced in the process of phage therapy need to be evaluated. In this study, two Podoviridae phages, hvKpP1 and hvKpP2, were isolated and characterized. In vitro and in vivo experiments demonstrated that the virulence of the resistant bacteria was significantly reduced compared with that of the wild type. Comparative genomic analysis of monoclonal sequencing showed that nucleotide deletion mutations of wzc and wcaJ genes led to phage resistance, and the electron microscopy and mucoviscosity results showed that mutations led to the loss of the capsule. Meanwhile, animal assay indicated that loss of capsule reduced the virulence of hvKp. These findings contribute to a better understanding of bacteriophage therapy, which not only can kill bacteria directly but also can reduce the virulence of bacteria by phage screening.