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Phage-Encoded Depolymerase DepKP144 with Therapeutic Potential Against Both K1- and K2-Type Klebsiella pneumoniae

Ekaterina A Kondakova1, Natalia N Golosova1, Bogdana I Kravchuk1

  • 1Institute of Chemical Biology and Fundamental Medicine Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia.

International Journal of Molecular Sciences
|June 26, 2026
PubMed

Insights

A novel phage depolymerase, DepKP144, effectively degrades multidrug-resistant Klebsiella pneumoniae capsules and biofilms. This enzyme shows promise as a therapeutic agent against challenging bacterial infections.

Area of Science:

  • Microbiology
  • Biotechnology
  • Infectious Diseases

Background:

  • Multidrug resistance (MDR) in bacteria poses a significant global health threat, complicating treatment and increasing patient mortality.
  • Klebsiella pneumoniae is a major cause of hospital-acquired infections, with MDR strains presenting a particular challenge.

Purpose of the Study:

  • To produce and characterize a recombinant phage-encoded depolymerase, DepKP144, for its potential therapeutic application against MDR K. pneumoniae.
  • To evaluate the efficacy of DepKP144 in degrading K. pneumoniae capsules, reducing bacterial viability, and disrupting biofilms.

Main Methods:

  • Recombinant expression and purification of phage-encoded depolymerase DepKP144 using Escherichia coli.
  • In vitro assessment of DepKP144 activity against planktonic K. pneumoniae cells (K1 and K2 types) and clinical MDR strains.
  • In vivo efficacy studies in mouse models of K. pneumoniae infection.

Main Results:

  • DepKP144 successfully reduced viable bacterial counts by degrading capsules in 95% of K1 and 85% of K2 K. pneumoniae strains.
  • The depolymerase demonstrated activity against planktonic cells and effectively destroyed biofilms formed by clinical MDR K. pneumoniae.
  • In vivo, DepKP144 administration improved survival rates in mice infected with K. pneumoniae, with 50% survival for K2 and 17% for K1 types.

Conclusions:

  • Recombinant DepKP144 is a potent enzyme capable of targeting and degrading K. pneumoniae, including MDR strains.
  • DepKP144 shows significant potential as a therapeutic candidate for combating infections caused by multidrug-resistant Klebsiella pneumoniae.
Keywords:
K. pneumoniaeK1-typeK2-typeKlebsiella pneumoniaeantibacterialsbiofilm degradationcapsular polysaccharidedepolymerasemulti drug resistance

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