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...
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MDPI AG
2021-02-01
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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. |
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last_indexed | 2024-03-09T06:09:19Z |
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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 |
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