Identification of a Depolymerase Specific for K64-Serotype <i>Klebsiella pneumoniae:</i> Potential Applications in Capsular Typing and Treatment

Carbapenem-resistant <i>Klebsiella pneumoniae</i> (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 identifi...

Full description

Bibliographic Details
Main Authors: Jiayin Li, Yueying Sheng, Ruijing Ma, Mengsha Xu, Fuli Liu, Rong Qin, Mingxi Zhu, Xianchao Zhu, Ping He
Format: Article
Language:English
Published: MDPI AG 2021-02-01
Series:Antibiotics
Subjects:
Online Access:https://www.mdpi.com/2079-6382/10/2/144
_version_ 1797416793857327104
author Jiayin Li
Yueying Sheng
Ruijing Ma
Mengsha Xu
Fuli Liu
Rong Qin
Mingxi Zhu
Xianchao Zhu
Ping He
author_facet Jiayin Li
Yueying Sheng
Ruijing Ma
Mengsha Xu
Fuli Liu
Rong Qin
Mingxi Zhu
Xianchao Zhu
Ping He
author_sort Jiayin Li
collection DOAJ
description Carbapenem-resistant <i>Klebsiella pneumoniae</i> (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 <i>Klebsiella</i> phage SH-KP152410, which showed specific activities for <i>K. pneumoniae</i> 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 <i>wzi</i>-sequencing based genotyping and depolymerase-based or antiserum-based typing methods. Further investigation indicated that the mutant strain has an insertion sequence (IS) in <i>wcaJ</i>, 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.
first_indexed 2024-03-09T06:09:19Z
format Article
id doaj.art-535c6207d1904302982be1b1efa1665f
institution Directory Open Access Journal
issn 2079-6382
language English
last_indexed 2024-03-09T06:09:19Z
publishDate 2021-02-01
publisher MDPI AG
record_format Article
series Antibiotics
spelling doaj.art-535c6207d1904302982be1b1efa1665f2023-12-03T12:00:16ZengMDPI AGAntibiotics2079-63822021-02-0110214410.3390/antibiotics10020144Identification of a Depolymerase Specific for K64-Serotype <i>Klebsiella pneumoniae:</i> Potential Applications in Capsular Typing and TreatmentJiayin Li0Yueying Sheng1Ruijing Ma2Mengsha Xu3Fuli Liu4Rong Qin5Mingxi Zhu6Xianchao Zhu7Ping He8Department of Medical Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaCollege of Medical Technology, Shanghai University of Medicine & Health Sciences, Shanghai 201318, ChinaShanghai Ruizhou Biotech Co. Ltd., Pudong New District, Shanghai 201203, ChinaDepartment of Medical Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaDepartment of Medical Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaDepartment of Medical Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaDepartment of Medical Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaShanghai Ruizhou Biotech Co. Ltd., Pudong New District, Shanghai 201203, ChinaDepartment of Medical Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaCarbapenem-resistant <i>Klebsiella pneumoniae</i> (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 <i>Klebsiella</i> phage SH-KP152410, which showed specific activities for <i>K. pneumoniae</i> 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 <i>wzi</i>-sequencing based genotyping and depolymerase-based or antiserum-based typing methods. Further investigation indicated that the mutant strain has an insertion sequence (IS) in <i>wcaJ</i>, 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.https://www.mdpi.com/2079-6382/10/2/144<i>Klebsiella pneumoniae</i>bacteriophagecapsular depolymerasecapsular typingantivirulence
spellingShingle Jiayin Li
Yueying Sheng
Ruijing Ma
Mengsha Xu
Fuli Liu
Rong Qin
Mingxi Zhu
Xianchao Zhu
Ping He
Identification of a Depolymerase Specific for K64-Serotype <i>Klebsiella pneumoniae:</i> Potential Applications in Capsular Typing and Treatment
Antibiotics
<i>Klebsiella pneumoniae</i>
bacteriophage
capsular depolymerase
capsular typing
antivirulence
title Identification of a Depolymerase Specific for K64-Serotype <i>Klebsiella pneumoniae:</i> Potential Applications in Capsular Typing and Treatment
title_full Identification of a Depolymerase Specific for K64-Serotype <i>Klebsiella pneumoniae:</i> Potential Applications in Capsular Typing and Treatment
title_fullStr Identification of a Depolymerase Specific for K64-Serotype <i>Klebsiella pneumoniae:</i> Potential Applications in Capsular Typing and Treatment
title_full_unstemmed Identification of a Depolymerase Specific for K64-Serotype <i>Klebsiella pneumoniae:</i> Potential Applications in Capsular Typing and Treatment
title_short Identification of a Depolymerase Specific for K64-Serotype <i>Klebsiella pneumoniae:</i> Potential Applications in Capsular Typing and Treatment
title_sort identification of a depolymerase specific for k64 serotype i klebsiella pneumoniae i potential applications in capsular typing and treatment
topic <i>Klebsiella pneumoniae</i>
bacteriophage
capsular depolymerase
capsular typing
antivirulence
url https://www.mdpi.com/2079-6382/10/2/144
work_keys_str_mv AT jiayinli identificationofadepolymerasespecificfork64serotypeiklebsiellapneumoniaeipotentialapplicationsincapsulartypingandtreatment
AT yueyingsheng identificationofadepolymerasespecificfork64serotypeiklebsiellapneumoniaeipotentialapplicationsincapsulartypingandtreatment
AT ruijingma identificationofadepolymerasespecificfork64serotypeiklebsiellapneumoniaeipotentialapplicationsincapsulartypingandtreatment
AT mengshaxu identificationofadepolymerasespecificfork64serotypeiklebsiellapneumoniaeipotentialapplicationsincapsulartypingandtreatment
AT fuliliu identificationofadepolymerasespecificfork64serotypeiklebsiellapneumoniaeipotentialapplicationsincapsulartypingandtreatment
AT rongqin identificationofadepolymerasespecificfork64serotypeiklebsiellapneumoniaeipotentialapplicationsincapsulartypingandtreatment
AT mingxizhu identificationofadepolymerasespecificfork64serotypeiklebsiellapneumoniaeipotentialapplicationsincapsulartypingandtreatment
AT xianchaozhu identificationofadepolymerasespecificfork64serotypeiklebsiellapneumoniaeipotentialapplicationsincapsulartypingandtreatment
AT pinghe identificationofadepolymerasespecificfork64serotypeiklebsiellapneumoniaeipotentialapplicationsincapsulartypingandtreatment