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Genetic determinants of hypervirulence with attenuated pathogenicity in a blaNDM-1-encoding Klebsiella pneumoniae

Deblina Nath1, Rinita Dhar1, Amrita Bhattacharjee1

  • 1Division of Bacteriology, ICMR National Institute for Research in Bacterial Infections (ICMR-NIRBI), Kolkata, India.

Virulence
|June 16, 2026
PubMed

Insights

A novel hypervirulent Klebsiella pneumoniae strain (K39) acquired a plasmid conferring carbapenem resistance and hypervirulence. Despite mutations leading to attenuated virulence in adult mice, it caused sepsis in a neonate, highlighting plasmid co-transmission risks.

Area of Science:

  • Microbiology and Infectious Diseases
  • Genomics and Molecular Biology
  • Antimicrobial Resistance

Background:

  • Hypervirulent Klebsiella pneumoniae (hvKP) strains are an emerging threat, causing severe infections.
  • The K39 serotype was previously unrecognized and its virulence determinants were uncharacterized.
  • Carbapenem resistance in hvKP complicates treatment options.

Purpose of the Study:

  • To investigate the genetic basis of hypervirulence in a K39 Klebsiella pneumoniae isolate (Sil80).
  • To assess the acquisition and functional expression of virulence and antimicrobial resistance determinants.
  • To evaluate the transmissibility of acquired plasmids and the isolate's virulence potential.

Main Methods:

  • Plasmid analysis, including transmissibility and functional expression of virulence genes (e.g., rmpA, iucA).
  • Capsule visualization via transmission electron microscopy (TEM).
  • Comparative genomics, in vitro assays (biofilm, serum resistance), and in vivo virulence assays in mice.

Main Results:

  • The carbapenem-resistant ST985-K39 isolate (Sil80) harbored a hypervirulent plasmid (IncFIB(K)/IncHI1B) and a carbapenemase-encoding plasmid (IncFIB(pQIL)/IncFII(K)).
  • The hypervirulent plasmid was co-transmitted with the IncFII plasmid due to nic site similarity, while the resistance plasmid was self-conjugative.
  • Sil80 exhibited serum resistance and biofilm formation but showed attenuated virulence in adult mice due to mutations in rmpADC promoter and truncated RmpD, despite possessing hypervirulence determinants.

Conclusions:

  • The K39 isolate acquired both hypervirulence and carbapenem resistance plasmids, with the latter facilitating the spread of the former.
  • Mutations in the rmpADC promoter and RmpD protein attenuated virulence in adult mice but did not prevent neonatal sepsis.
  • This study demonstrates a mechanism for the spread of virulence plasmids to new serotypes via co-transmission with conjugative plasmids.
Keywords:
carbapenem resistancehypervirulent Klebsiella pneumoniaenic sitepoly T-trackrmpADC cascadermpD

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