Characterization and Functional Studies of a Novel Depolymerase Against K19-Type Klebsiella pneumoniae.

Characterization and Functional Studies of a Novel Depolymerase Against K19-Type Klebsiella pneumoniae.
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针对K19型克雷伯氏菌肺炎的新型解聚酶的表征和功能研究。

DOI:
10.3389/fmicb.2022.878800
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发表时间:
2022
影响因子:
5.2
通讯作者:
--
中科院分区:
生物学2区
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耐碳青霉烯类肺炎克雷伯菌(CRKP)是一种引起严重医院感染和高死亡率的病原菌,由于其高度的耐药性,对全球公共卫生构成严重威胁。噬菌体编码多糖降解酶,称为解聚酶,裂解肺炎克雷伯菌主要毒力因子之一的衣壳多糖(CPS)。在本研究中,我们从肺炎克雷伯菌噬菌体SH-KP156570中鉴定并鉴定了一个新的胶囊去聚合酶K19-Dpo41。我们对K19-Dpo41的鉴定表明,该解聚酶具有抗K19型肺炎克雷伯菌的特异性。K19-Dpo41介导的治疗提高了K19型肺炎克雷伯菌多药耐药株对人血清杀菌作用的敏感性,并显著提高了感染K19型肺炎克雷伯菌的梅隆格列氏菌的存活率。我们的结果提供了强有力的初步证据,表明K19-Dpo41不仅在K19型肺炎克雷伯菌的包膜分型中有效,而且在未来开发针对K19型CRKP感染的新的替代治疗策略方面也是有前景的。
Carbapenem-resistant Klebsiella pneumoniae (CRKP), a pathogen that causes severe nosocomial infections and yields a high mortality rate, poses a serious threat to global public health due to its high antimicrobial resistance. Bacteriophages encode polysaccharide-degrading enzymes referred to as depolymerases that cleave the capsular polysaccharide (CPS), one of the main virulence factors of K. pneumoniae. In this study, we identified and characterized a new capsule depolymerase K19-Dpo41 from K. pneumoniae bacteriophage SH-KP156570. Our characterization of K19-Dpo41 demonstrated that this depolymerase showed specific activities against K19-type K. pneumoniae. K19-Dpo41-mediated treatments promoted the sensitivity of a multidrug-resistant K19-type K. pneumoniae strain to the bactericidal effect of human serum and significantly increased the survival rate of Galleria mellonella infected with K19-type K. pneumoniae. Our results provided strong primary evidence that K19-Dpo41 was not only effective in capsular typing of K19-type K. pneumoniae but promising in terms of developing new alternative therapeutic strategies against K19-type CRKP infections in the future.