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Testing the Role of Multicopy Plasmids in the Evolution of Antibiotic Resistance
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Molecular dissection of the evolution of carbapenem-resistant multilocus sequence type 258 Klebsiella pneumoniae

Frank R Deleo1, Liang Chen, Stephen F Porcella

  • 1Laboratory of Human Bacterial Pathogenesis and Research Technologies Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840.

Proceedings of the National Academy of Sciences of the United States of America
|March 19, 2014
PubMed

Insights

Carbapenem-resistant Klebsiella pneumoniae ST258 is not a single clone but two distinct genetic clades. This finding challenges previous assumptions and opens new avenues for combating drug-resistant bacterial infections.

Area of Science:

  • Microbiology
  • Genomics
  • Infectious Diseases

Background:

  • Drug-resistant bacterial infections pose a significant global health threat.
  • Carbapenem-resistant Klebsiella pneumoniae, particularly sequence type (ST) 258, is a leading cause of hospital-acquired infections and mortality.
  • The prevalence and success of the ST258 lineage in causing multidrug-resistant infections remain incompletely understood.

Purpose of the Study:

  • To investigate the genetic relatedness of carbapenem-resistant Klebsiella pneumoniae ST258 isolates.
  • To test the hypothesis that ST258 represents a single, globally disseminated genetic clone.
  • To identify genetic factors contributing to the success of ST258 K. pneumoniae.

Main Methods:

  • Whole-genome sequencing of two ST258 clinical isolates.
  • Comparative genome sequencing of 83 additional ST258 clinical isolates from diverse geographic locations.
  • Phylogenetic analysis of single nucleotide polymorphisms (SNPs) in the core genome.

Main Results:

  • Phylogenetic analysis revealed that ST258 K. pneumoniae comprises two distinct genetic clades, refuting the single-clone hypothesis.
  • A significant region of divergence (approximately 215 kb), including genes for capsule polysaccharide biosynthesis, differentiates the two clades.
  • This region of divergence appears to be a recombination hotspot, potentially contributing to the lineage's success.

Conclusions:

  • Carbapenem-resistant K. pneumoniae ST258 is not a monolithic clone but exists as two genetically distinct clades.
  • The identified region of divergence is a key area for further research into ST258 evolution and virulence.
  • These findings are crucial for developing targeted diagnostic, therapeutic, and vaccine strategies against multidrug-resistant K. pneumoniae infections.
Keywords:
Enterobacteriaceaeantibiotic resistancecarbapenemaseplasmid

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