Identification of three podoviruses infecting Klebsiella encoding capsule depolymerases that digest specific capsular types

Identification of three podoviruses infecting Klebsiella encoding capsule depolymerases that digest specific capsular types

Summary Klebsiella pneumoniae is an important human pathogen causing opportunistic nosocomial and community‐acquired infections. A major public health concern regarding K. pneumoniae is the increasing incidence of multidrug‐resistant strains. Here, we isolated three novel Klebsiella bacteriophages,...

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Published in:Microbial biotechnology Vol. 12; no. 3; pp. 472 - 486
Main Authors: Pan, Yi‐Jiun, Lin, Tzu‐Lung, Chen, Yi‐Yin, Lai, Peng‐Hsuan, Tsai, Yun‐Ting, Hsu, Chun‐Ru, Hsieh, Pei‐Fang, Lin, Yi‐Tsung, Wang, Jin‐Town
Format: Journal Article
Language:English
Published: United States John Wiley & Sons, Inc 01-05-2019
John Wiley and Sons Inc
Subjects:
Bacteria
Comparative analysis
Drug resistance
Enzymatic activity
Enzymes
Gene sequencing
Genomes
Hospitals
Host range
Host specificity
Kinases
Klebsiella
Nosocomial infection
Nosocomial infections
Opportunist infection
Pathogens
Phages
Pneumonia
Public health
Urogenital system
Variable region
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Summary:Summary Klebsiella pneumoniae is an important human pathogen causing opportunistic nosocomial and community‐acquired infections. A major public health concern regarding K. pneumoniae is the increasing incidence of multidrug‐resistant strains. Here, we isolated three novel Klebsiella bacteriophages, KN1‐1, KN3‐1 and KN4‐1, which infect KN1, KN3 and K56, and KN4 types respectively. We determined their genome sequences and conducted a comparative analysis that revealed a variable region containing capsule depolymerase‐encoding genes. Recombinant depolymerase proteins were produced, and their enzymatic activity and specificity were evaluated. We identified four capsule depolymerases in these phages that could only digest the capsule types of their respective hosts. Our results demonstrate that the activities of these capsule depolymerases were correlated with the host range of each phage; thus, the capsule depolymerases are host specificity determinants. By generating a capsule mutant, we demonstrate that capsule was essential for phage adsorption and infection. Further, capsule depolymerases can enhance bacterial susceptibility to serum killing. The discovery of these phages and depolymerases lays the foundation for the typing of KN1, KN3, KN4 and K56 Klebsiella and could be useful alternative therapeutics for the treatment of K. pneumoniae infections. We report three novel Klebsiella phages, KN1‐1, KN3‐1, and KN4‐1, infecting KN1; KN3 and K56; and KN4 types, respectively. We further identified the specific capsule depolymerases of these phages. The discovery of these phages and depolymerases lays the foundation for typing of KN1, KN3, KN4, and K56 Klebsiella and may be used as alternative therapeutics for the treatment of K. pneumoniae infections.
Bibliography:This study was supported by grants from the Ministry of Science and Technology, National Taiwan University, National Taiwan University Hospital, China Medical University (Grant Nos. CMU105‐N‐12 and CMU106‐N‐03), and China Medical University Hospital (DMR‐108‐136).
Funding Information
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ISSN:1751-7915
1751-7915
DOI:10.1111/1751-7915.13370