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Phage-borne depolymerases decrease Klebsiella pneumoniae resistance to innate defense mechanisms

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Abstract
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 beta-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 serum-resistant 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.
Keywords
bacteriophage, Klebsiella sp., capsule, polysaccharide depolymerase, innate immunity, O SIDE-CHAIN, CAPSULAR POLYSACCHARIDE, CRYSTAL-STRUCTURE, BACTERIOPHAGE, COMPLEMENT, INFECTION, PROTEINS, IDENTIFICATION, VIRULENCE, K1

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Chicago
Majkowska-Skrobek, Grazyna, Agnieszka Łątka, Rita Berisio, Flavia Squeglia, Barbara Maciejewska, Yves Briers, and Zuzanna Drulis-Kawa. 2018. “Phage-borne Depolymerases Decrease Klebsiella Pneumoniae Resistance to Innate Defense Mechanisms.” Frontiers in Microbiology 9.
APA
Majkowska-Skrobek, G., Łątka, A., Berisio, R., Squeglia, F., Maciejewska, B., Briers, Y., & Drulis-Kawa, Z. (2018). Phage-borne depolymerases decrease Klebsiella pneumoniae resistance to innate defense mechanisms. FRONTIERS IN MICROBIOLOGY, 9.
Vancouver
1.
Majkowska-Skrobek G, Łątka A, Berisio R, Squeglia F, Maciejewska B, Briers Y, et al. Phage-borne depolymerases decrease Klebsiella pneumoniae resistance to innate defense mechanisms. FRONTIERS IN MICROBIOLOGY. 2018;9.
MLA
Majkowska-Skrobek, Grazyna, Agnieszka Łątka, Rita Berisio, et al. “Phage-borne Depolymerases Decrease Klebsiella Pneumoniae Resistance to Innate Defense Mechanisms.” FRONTIERS IN MICROBIOLOGY 9 (2018): n. pag. Print.
@article{8581068,
  abstract     = {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 beta-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 serum-resistant 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.},
  articleno    = {2517},
  author       = {Majkowska-Skrobek, Grazyna and \unmatched{0141}\k{a}tka, Agnieszka and Berisio, Rita and Squeglia, Flavia and Maciejewska, Barbara and Briers, Yves and Drulis-Kawa, Zuzanna},
  issn         = {1664-302X},
  journal      = {FRONTIERS IN MICROBIOLOGY},
  language     = {eng},
  pages        = {12},
  title        = {Phage-borne depolymerases decrease Klebsiella pneumoniae resistance to innate defense mechanisms},
  url          = {http://dx.doi.org/10.3389/fmicb.2018.02517},
  volume       = {9},
  year         = {2018},
}

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