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Anti-plasmid defense in hypervirulent Klebsiella pneumoniae involves Type I-like and Type IV restriction modification

Guodong Oo1, Wen Wen Low1, Melvin Yong1

  • 1Infectious Diseases Translational Research Programme, Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Emerging Microbes & Infections
|September 8, 2025
PubMed

Insights

Hypervirulent Klebsiella pneumoniae strains can acquire antibiotic resistance via plasmid transfer. This study identifies restriction modification systems that limit plasmid uptake, explaining the emergence of multidrug-resistant hypervirulent strains.

Area of Science:

  • Microbiology
  • Genetics
  • Infectious Diseases

Background:

  • Hypervirulent Klebsiella pneumoniae (hvKp) strains are typically resistant to plasmid acquisition due to hypermucoid capsules.
  • The convergence of hypervirulence and multidrug resistance (MDR) in K. pneumoniae is a growing global health concern.

Purpose of the Study:

  • To investigate the susceptibility of hvKp strains to horizontal gene transfer (HGT), specifically plasmid acquisition.
  • To identify genetic mechanisms, such as restriction modification (RM) systems, that may limit plasmid transfer in hvKp.

Main Methods:

  • Profiling 127 antibiotic-susceptible hvKp strains for plasmid transfer permissiveness.
  • Identifying and characterizing RM systems in hvKp strains exhibiting low plasmid uptake.
  • Analyzing the regulation of RM systems by metabolic pathways (L-arginine, spermidine, S-adenosyl methionine).

Main Results:

  • Most (86%) antibiotic-susceptible hvKp strains were highly permissive to plasmid transfer.
  • Two RM systems (McrBC and a unique Type I RM system) were identified in low-permissiveness strains, effectively inhibiting plasmid uptake.
  • L-arginine and spermidine metabolism, regulated by S-adenosyl methionine, controls the Type I-like RM system.
  • Strains lacking these RM systems showed high plasmid receptivity, correlating with antibiotic resistance in clinical isolates.

Conclusions:

  • hvKp strains are generally susceptible to plasmid transfer, contrary to previous assumptions.
  • Unusual RM systems act as a defense against plasmid acquisition in some hvKp strains.
  • The interplay between plasmid evolution and host defense mechanisms, alongside the rarity of these RM systems, contributes to the emergence of MDR hvKp strains.
Keywords:
Klebsiella pneumoniaedefensehypervirulentplasmidrestriction modification

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