Identification of three podoviruses infecting Klebsiella encoding capsule depolymerases that digest specific capsular types
Identification of three podoviruses infecting Klebsiella encoding capsule depolymerases that digest specific capsular types
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DOI：
10.1111/1751-7915.13370
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发表时间：
2019-05-01
影响因子：
5.7
通讯作者：
Wang, Jin-Town
中科院分区：
文献类型：
--
作者：
Pan, Yi-Jiun;Lin, Tzu-Lung;Wang, Jin-Town
肺炎克雷伯菌是引起医院和社区获得性机会感染的重要病原体。关于肺炎克雷伯菌的一个主要公共卫生问题是多重耐药菌株的发生率不断增加。在这里，我们分离了三种新的克雷伯氏菌噬菌体，KN 1 -1，KN 3 -1和KN 4 -1，它们分别感染KN 1，KN 3和K56和KN 4型。我们确定了它们的基因组序列，并进行了比较分析，揭示了一个可变区含有胶囊解聚酶编码基因。生产重组解聚酶蛋白，并评价其酶活性和特异性。我们确定了四个胶囊解聚酶在这些大肠杆菌，只能消化胶囊类型的各自的主机。我们的研究结果表明，这些胶囊解聚酶的活动与每个噬菌体的宿主范围，因此，胶囊解聚酶的宿主特异性决定因素。通过产生胶囊突变体，我们证明了胶囊是噬菌体吸附和感染所必需的。此外，胶囊解聚酶可以增强细菌对血清杀伤的易感性。这些聚合酶和解聚酶的发现为KN 1、KN 3、KN 4和K56克雷伯菌的分型奠定了基础，并可能成为治疗肺炎克雷伯菌感染的有用的替代疗法。
Klebsiella pneumoniae is an important human pathogen causing opportunistic nosocomial and community-acquired infections. A major public health concern regarding K.pneumoniae is the increasing incidence of multidrug-resistant strains. Here, we isolated three novel Klebsiella bacteriophages, KN1-1, KN3-1 and KN4-1, which infect KN1, KN3 and K56, and KN4 types respectively. We determined their genome sequences and conducted a comparative analysis that revealed a variable region containing capsule depolymerase-encoding genes. Recombinant depolymerase proteins were produced, and their enzymatic activity and specificity were evaluated. We identified four capsule depolymerases in these phages that could only digest the capsule types of their respective hosts. Our results demonstrate that the activities of these capsule depolymerases were correlated with the host range of each phage; thus, the capsule depolymerases are host specificity determinants. By generating a capsule mutant, we demonstrate that capsule was essential for phage adsorption and infection. Further, capsule depolymerases can enhance bacterial susceptibility to serum killing. The discovery of these phages and depolymerases lays the foundation for the typing of KN1, KN3, KN4 and K56 Klebsiella and could be useful alternative therapeutics for the treatment of K.pneumoniae infections.