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A novel phage putative depolymerase, Depo16, has specific activity against K1 capsular-type Klebsiella pneumoniae

Rihong Zhao1, Shanshan Jiang1, Siyu Ren1

  • 1State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun, China.

Applied and Environmental Microbiology
|March 29, 2024
PubMed

Insights

A novel phage depolymerase, Depo16, effectively degrades the K1 capsule of hypervirulent Klebsiella pneumoniae (hvKP). This treatment enhances bacterial sensitivity to macrophages and shows therapeutic potential in a mouse bacteremia model.

Area of Science:

  • Microbiology
  • Bacteriology
  • Virology

Background:

  • Klebsiella pneumoniae, particularly hypervirulent strains (hvKP), is a significant cause of hospital and community infections.
  • The capsular polysaccharide (CPS) is a key virulence factor for K. pneumoniae, with K1 and K2 serotypes being most prevalent in hvKP.
  • Bacteriophages can encode depolymerases that degrade bacterial polysaccharides, offering potential antimicrobial strategies.

Purpose of the Study:

  • To isolate and characterize a novel lytic bacteriophage and its depolymerase against serotype K1 hvKP.
  • To evaluate the efficacy of the depolymerase in vitro and in vivo as a potential antibacterial agent.

Main Methods:

  • Isolation of lytic bacteriophage vB_KpnP_ZK1 (ZK1) using serotype K1 hvKP.
  • Expression and purification of the putative depolymerase, Depo16, from phage ZK1.
  • Assessment of Depo16's ability to degrade K1 CPS and enhance bacterial susceptibility to macrophages.
  • Evaluation of Depo16's therapeutic effect in a mouse model of K1 K. pneumoniae bacteremia.

Main Results:

  • Depo16 efficiently removed the capsular polysaccharide layer from serotype K1 K. pneumoniae.
  • Depo16 treatment sensitized K1 K. pneumoniae to peritoneal macrophages.
  • In a mouse bacteremia model, 25 µg of Depo16 significantly prolonged survival and reduced bacterial load.
  • Depo16 treatment alleviated tissue damage in infected mice.

Conclusions:

  • The putative depolymerase Depo16, despite low homology to known depolymerases, exhibits significant enzymatic activity against K1 CPS.
  • Depo16 enhances the host immune response against K1 K. pneumoniae by increasing macrophage phagocytosis.
  • Depo16 demonstrates significant therapeutic potential as an antibacterial agent for serotype K1 K. pneumoniae infections.
Keywords:
Klebsiella pneumoniaebacteremiaphage depolymerasesserotype K1

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