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

Carbapenem-resistant Klebsiella pneumoniae (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 characterize...

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Autores principales: Li, Jiayin, Sheng, Yueying, Ma, Ruijing, Xu, Mengsha, Liu, Fuli, Qin, Rong, Zhu, Mingxi, Zhu, Xianchao, He, Ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912862/
https://www.ncbi.nlm.nih.gov/pubmed/33535705
http://dx.doi.org/10.3390/antibiotics10020144
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author Li, Jiayin
Sheng, Yueying
Ma, Ruijing
Xu, Mengsha
Liu, Fuli
Qin, Rong
Zhu, Mingxi
Zhu, Xianchao
He, Ping
author_facet Li, Jiayin
Sheng, Yueying
Ma, Ruijing
Xu, Mengsha
Liu, Fuli
Qin, Rong
Zhu, Mingxi
Zhu, Xianchao
He, Ping
author_sort Li, Jiayin
collection PubMed
description Carbapenem-resistant Klebsiella pneumoniae (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 Klebsiella phage SH-KP152410, which showed specific activities for K. pneumoniae 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 wzi-sequencing based genotyping and depolymerase-based or antiserum-based typing methods. Further investigation indicated that the mutant strain has an insertion sequence (IS) in wcaJ, 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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spelling pubmed-79128622021-02-28 Identification of a Depolymerase Specific for K64-Serotype Klebsiella pneumoniae: Potential Applications in Capsular Typing and Treatment Li, Jiayin Sheng, Yueying Ma, Ruijing Xu, Mengsha Liu, Fuli Qin, Rong Zhu, Mingxi Zhu, Xianchao He, Ping Antibiotics (Basel) Article Carbapenem-resistant Klebsiella pneumoniae (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 Klebsiella phage SH-KP152410, which showed specific activities for K. pneumoniae 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 wzi-sequencing based genotyping and depolymerase-based or antiserum-based typing methods. Further investigation indicated that the mutant strain has an insertion sequence (IS) in wcaJ, 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. MDPI 2021-02-01 /pmc/articles/PMC7912862/ /pubmed/33535705 http://dx.doi.org/10.3390/antibiotics10020144 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Li, Jiayin
Sheng, Yueying
Ma, Ruijing
Xu, Mengsha
Liu, Fuli
Qin, Rong
Zhu, Mingxi
Zhu, Xianchao
He, Ping
Identification of a Depolymerase Specific for K64-Serotype Klebsiella pneumoniae: Potential Applications in Capsular Typing and Treatment
title Identification of a Depolymerase Specific for K64-Serotype Klebsiella pneumoniae: Potential Applications in Capsular Typing and Treatment
title_full Identification of a Depolymerase Specific for K64-Serotype Klebsiella pneumoniae: Potential Applications in Capsular Typing and Treatment
title_fullStr Identification of a Depolymerase Specific for K64-Serotype Klebsiella pneumoniae: Potential Applications in Capsular Typing and Treatment
title_full_unstemmed Identification of a Depolymerase Specific for K64-Serotype Klebsiella pneumoniae: Potential Applications in Capsular Typing and Treatment
title_short Identification of a Depolymerase Specific for K64-Serotype Klebsiella pneumoniae: Potential Applications in Capsular Typing and Treatment
title_sort identification of a depolymerase specific for k64-serotype klebsiella pneumoniae: potential applications in capsular typing and treatment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912862/
https://www.ncbi.nlm.nih.gov/pubmed/33535705
http://dx.doi.org/10.3390/antibiotics10020144
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