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Identification of a phage-derived depolymerase specific for KL47 capsule of Klebsiella pneumoniae and its therapeutic potential in mice

文献类型： 外文期刊

作者： Li, Min 1 ; Wang, Hui 1 ; Chen, Long 4 ; Guo, Genglin 1 ; Li, Pei 1 ; Ma, Jiale 1 ; Chen, Rong 5 ; Du, Hong 6 ; Liu, Yuqing 7 ; Zhang, Wei 1 ;

作者机构： 1.Nanjing Agr Univ, Coll Vet Med, Nanjing 210095, Peoples R China

2.Minist Agr, Key Lab Anim Bacteriol, Nanjing 210095, Peoples R China

3.Nanjing Agr Univ, Coll Vet Med, MOE Joint Int Res Lab Anim Hlth & Food Safety, Nanjing 210095, Peoples R China

4.Soochow Univ, Dept Clin Lab, Zhangjiagang Hosp, Zhangjiagang 215600, Peoples R China

5.Jiangsu Acad Agr Sci, Inst Vet Med, Nanjing 210014, Peoples R China

6.Soochow Univ, Dept Clin Lab, Affiliated Hosp 2, Suzhou 215004, Peoples R China

7.Shandong Acad Agr Sci, Inst Anim Sci & Vet Med, Jinan 250100, Peoples R China

关键词： Bacteriophage-derived depolymerase; Carbapenem-resistant Klebsiella pneumoniae; Capsular type; Biofilm; Antimicrobial therapy

期刊名称：VIROLOGICA SINICA （ 影响因子：6.947； 五年影响因子：5.997 ）

ISSN： 1674-0769

年卷期： 2022 年 37 卷 4 期

页码：

收录情况： SCI

摘要： Klebsiella pneumoniae is one of the major pathogens causing global multidrug-resistant infections. Therefore, strategies for preventing and controlling the infections are urgently needed. Phage depolymerase, often found in the tail fiber protein or the tail spike protein, is reported to have antibiofilm activity. In this study, phage P560 isolated from sewage showed specific for capsule locus type KL47 K. pneumoniae, and the enlarged haloes around plaques indicated that P560 encoded a depolymerase. The capsule depolymerase, ORF43, named P560dep, derived from phage P560 was expressed, purified, characterized and evaluated for enzymatic activity as well as specificity. We reported that the capsule depolymerase P560dep, can digest the capsule polysaccharides on the surface of KL47 type K. pneumoniae, and the depolymerization spectrum of P560dep matched to the host range of phage P560, KL47 K. pneumoniae. Crystal violet staining assay showed that P560dep was able to significantly inhibit biofilm formation. Further, a single dose (50 mu g/mouse) of depolymerase intraperitoneal injection pro-tected 90%-100% of mice from lethal challenge before or after infection by KL47 carbapenem-resistant K. pneumoniae. And pathological changes were alleviated in lung and liver of mice infected by KL47 type K. pneumoniae. It is demonstrated that depolymerase P560dep as an attractive antivirulence agent represents a promising tool for antimicrobial therapy.

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