Phage-Borne Depolymerases Decrease Klebsiella pneumoniae Resistance to Innate Defense Mechanisms (1941 views)
Front Microbiol (ISSN: 1664-302xprint, 1664-302xlinking, 1664-302xelectronic), 2018 Oct 23; 9(OCT): 2517-2517.
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Paper type: Journal Article,
Impact factor: 4.076, 5-year impact factor: 4.526
Url: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85055849009&doi=10.3389%2ffmicb.2018.02517&partnerID=40&md5=6fab09084e11aa36171d9b1bcb593160
Keywords: Klebsiella Sp, Bacteriophage, Capsule, Innate Immunity, Polysaccharide Depolymerase,
Affiliations:
*** IBB - CNR ***
Department of Pathogen Biology and Immunology, Institute of Genetics and Microbiology, University of Wroclaw, Wroclaw, Poland., Laboratory of Applied Biotechnology, Department of Biotechnology, Ghent University, Ghent, Belgium., Institute of Biostructure and Bioimaging, Italian National Research Council, Naples, Italy.,
References:
Not available.
Front Microbiol (ISSN: 1664-302xprint, 1664-302xlinking, 1664-302xelectronic), 2018 Oct 23; 9(OCT): 2517-2517.
Export to BibTeX Export to EndNote
Paper type: Journal Article,
Impact factor: 4.076, 5-year impact factor: 4.526
Url: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85055849009&doi=10.3389%2ffmicb.2018.02517&partnerID=40&md5=6fab09084e11aa36171d9b1bcb593160
Keywords: Klebsiella Sp, Bacteriophage, Capsule, Innate Immunity, Polysaccharide Depolymerase,
Affiliations:
*** IBB - CNR ***
Department of Pathogen Biology and Immunology, Institute of Genetics and Microbiology, University of Wroclaw, Wroclaw, Poland., Laboratory of Applied Biotechnology, Department of Biotechnology, Ghent University, Ghent, Belgium., Institute of Biostructure and Bioimaging, Italian National Research Council, Naples, Italy.,
References:
Not available.
Phage-Borne Depolymerases Decrease Klebsiella pneumoniae Resistance to Innate Defense Mechanisms
Klebsiella pneumoniae produces capsular polysaccharides that are a crucial virulence factor protecting bacteria against innate response mechanisms of the infected host. Simultaneously, those capsules are targeted by specific bacteriophages equipped with virion-associated depolymerases able to recognize and degrade these polysaccharides. We show that Klebsiella phage KP32 produces two capsule depolymerases, KP32gp37 and KP32gp38, with a high specificity for the capsular serotypes K3 and K21, respectively. Together, they determine the host spectrum of bacteriophage KP32, which is limited to strains with serotype K3 and K21. Both depolymerases form a trimeric β-structure, display moderate thermostability and function optimally under neutral to alkaline conditions. We show that both depolymerases strongly affect the virulence of K. pneumoniae with the corresponding K3 and K21 capsular serotypes. Capsule degradation renders the otherwise serumresistant cells more prone to complement-mediated killing with up to four log reduction in serum upon exposure to KP32gp37. Decapsulated strains are also sensitized for phagocytosis with a twofold increased uptake. In addition, the intracellular survival of phagocytized cells in macrophages was significantly reduced when bacteria were previously exposed to the capsule depolymerases. Finally, depolymerase application considerably increases the lifespan of Galleria mellonella larvae infected with K. pneumoniae in a time- and strain-dependent manner. In sum, capsule depolymerases are promising antivirulence compounds that act by defeating a major resistance mechanism of K. pneumoniae against the innate immunity. © 2018 Departamento de Enfermagem/Universidade Federal de Sao Paulo. All rights reserved.
Klebsiella pneumoniae produces capsular polysaccharides that are a crucial virulence factor protecting bacteria against innate response mechanisms of the infected host. Simultaneously, those capsules are targeted by specific bacteriophages equipped with virion-associated depolymerases able to recognize and degrade these polysaccharides. We show that Klebsiella phage KP32 produces two capsule depolymerases, KP32gp37 and KP32gp38, with a high specificity for the capsular serotypes K3 and K21, respectively. Together, they determine the host spectrum of bacteriophage KP32, which is limited to strains with serotype K3 and K21. Both depolymerases form a trimeric β-structure, display moderate thermostability and function optimally under neutral to alkaline conditions. We show that both depolymerases strongly affect the virulence of K. pneumoniae with the corresponding K3 and K21 capsular serotypes. Capsule degradation renders the otherwise serumresistant cells more prone to complement-mediated killing with up to four log reduction in serum upon exposure to KP32gp37. Decapsulated strains are also sensitized for phagocytosis with a twofold increased uptake. In addition, the intracellular survival of phagocytized cells in macrophages was significantly reduced when bacteria were previously exposed to the capsule depolymerases. Finally, depolymerase application considerably increases the lifespan of Galleria mellonella larvae infected with K. pneumoniae in a time- and strain-dependent manner. In sum, capsule depolymerases are promising antivirulence compounds that act by defeating a major resistance mechanism of K. pneumoniae against the innate immunity. © 2018 Departamento de Enfermagem/Universidade Federal de Sao Paulo. All rights reserved.
Phage-Borne Depolymerases Decrease Klebsiella pneumoniae Resistance to Innate Defense Mechanisms
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Phage-Borne Depolymerases Decrease Klebsiella pneumoniae Resistance to Innate Defense Mechanisms
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12 Records (12 excluding Abstracts).
Total impact factor: 45.121 (45.121 excluding Abstracts).
Total 5 year impact factor: 48.189 (48.189 excluding Abstracts).
Total impact factor: 45.121 (45.121 excluding Abstracts).
Total 5 year impact factor: 48.189 (48.189 excluding Abstracts).
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