Identification of a Depolymerase Specific for K64-Serotype Klebsiella pneumoniae: Potential Applications in Capsular Typing and Treatment.

Identification of a Depolymerase Specific for K64-Serotype Klebsiella pneumoniae: Potential Applications in Capsular Typing and Treatment.
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DOI:
10.3390/antibiotics10020144
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发表时间:
2021-02-01
期刊:
Antibiotics (Basel, Switzerland)
影响因子:
--
通讯作者:
He P
He P
中科院分区:
其他
文献类型:
--
作者:
Li J;Sheng Y;Ma R;Xu M;Liu F;Qin R;Zhu M;Zhu X;He P

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耐碳青霉烯类肺炎克雷伯菌(CRKP)是医院感染的主要病原菌之一,日益成为全球公共卫生的严重威胁。迫切需要制定有效的治疗和预防方法来对抗病原体。在这里,我们鉴定和表征了一种新的胶囊解聚酶(K64-ORF 41),它来自克雷伯氏菌噬菌体SH-KP 152410,显示出对K. pneumoniae K64血清型。结果表明,该解聚酶可用于K64血清型的分型,其结果与传统的抗血清分型方法一致。从这项研究中,我们还鉴定了K64突变株,其在基于wzi测序的基因分型和基于解聚酶或基于抗血清的分型方法之间显示出分型差异。进一步的研究表明,突变株在wcaJ中有一个插入序列(IS),这导致了荚膜血清型结构的改变。我们进一步证明了K64-ORF 41解聚酶可以通过降解荚膜多糖使细菌对血清或中性粒细胞杀伤敏感。总之,鉴定的K64解聚酶被证明是用于荚膜分型的准确和可靠的工具,这将有助于预防性干预,如疫苗开发。此外,该聚合酶可能是一种潜在的和有前途的治疗CRKP-K64感染的生物制剂。
Carbapenem-resistant Klebsiella pneumoniae (CRKP), one of the major nosocomial pathogens, is increasingly becoming a serious threat to global public health. There is an urgent need to develop effective therapeutic and preventive approaches to combat the pathogen. Here, we identified and characterized a novel capsule depolymerase (K64-ORF41) derived from Klebsiella phage SH-KP152410, which showed specific activities for K. pneumoniae K64-serotype. We showed that this depolymerase could be used in the identification of K64 serotypes based on the capsular typing, and the results agreed well with those from the conventional serotyping method using antisera. From this study, we also identified K64 mutant strains, which showed typing discrepancy between wzi-sequencing based genotyping and depolymerase-based or antiserum-based typing methods. Further investigation indicated that the mutant strain has an insertion sequence (IS) in wcaJ, which led to the alteration of the capsular serotype structure. We further demonstrated that K64-ORF41 depolymerase could sensitize the bacteria to serum or neutrophil killing by degrading the capsular polysaccharide. In summary, the identified K64 depolymerase proves to be an accurate and reliable tool for capsular typing, which will facilitate the preventive intervention such as vaccine development. In addition, the polymerase may represent a potential and promising therapeutic biologics against CRKP-K64 infections.
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