Identification of three capsule depolymerases in a bacteriophage infecting Klebsiella pneumoniae capsular types K7, K20, and K27 and therapeutic application

Journal of Biomedical Science

Research

Tzu-Lung Lin¹  Yi-Jiun Pan²  Ya-Zhu Liu²  Lii-Tzu Wu²  Jin-Town Wang³  Jia-Wen Wu⁴ 

[1] Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Taoyuan, Taiwan;Department of Microbiology and Immunology, School of Medicine, College of Medicine, China Medical University, No. 91 Hsueh-Shih Road, Taichung, Taiwan;Department of Microbiology, National Taiwan University College of Medicine, Taipei, Taiwan;Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan;Graduate Institute of Biomedical Sciences, College of Medicine, China Medical University, Taichung, Taiwan;Department of Microbiology and Immunology, School of Medicine, College of Medicine, China Medical University, No. 91 Hsueh-Shih Road, Taichung, Taiwan;

关键词: Klebsiella pneumoniae;    Hypervirulent;    Phage;    Capsule depolymerase;   

DOI  :  10.1186/s12929-023-00928-0

 received in 2023-02-01, accepted in 2023-05-12,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundKlebsiella pneumoniae capsular types K1, K2, K5, K20, K54, and K57 are prevalent hypervirulent types associated with community infections, and worrisomely, hypervirulent strains that acquired drug resistance have been found. In the search for alternative therapeutics, studies have been conducted on phages that infect K. pneumoniae K1, K2, K5, and K57-type strains and their phage-encoded depolymerases. However, phages targeting K. pneumoniae K20-type strains and capsule depolymerases capable of digesting K20-type capsules have rarely been reported. In this study, we characterized a phage that can infect K. pneumoniae K20-type strains, phage vB_KpnM‐20.MethodsA phage was isolated from sewage water in Taipei, Taiwan, its genome was analyzed, and its predicted capsule depolymerases were expressed and purified. The host specificity and capsule-digesting activity of the capsule depolymerases were determined. The therapeutic effect of the depolymerase targeting K. pneumoniae K20-type strains was analyzed in a mouse infection model.ResultsThe isolated Klebsiella phage, vB_KpnM‐20, infects K. pneumoniae K7, K20, and K27-type strains. Three capsule depolymerases, K7dep, K20dep, and K27dep, encoded by the phage were specific to K7, K20, and K27-type capsules, respectively. K20dep also recognized Escherichia coli K30-type capsule, which is highly similar to K. pneumoniae K20-type. The survival of K. pneumoniae K20-type-infected mice was increased following administration of K20dep.ConclusionsThe potential of capsule depolymerase K20dep for the treatment of K. pneumoniae infections was revealed using an in vivo infection model. In addition, K7dep, K20dep, and K27dep capsule depolymerases could be used for K. pneumoniae capsular typing.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

41116_2023_36_Article_IEq56.gif

41116_2023_36_Article_IEq28.gif

41116_2023_36_Article_IEq26.gif

41116_2023_36_Article_IEq24.gif

41116_2023_36_Article_IEq3.gif

Fig. 30

Fig. 4

40517_2023_256_Article_IEq150.gif

Fig. 27

Fig. 1