Genomic heterogeneity in Klebsiella pneumoniae strains is associated with primary pyogenic liver abscess and metastatic infection

J Infect Dis. 2005 Jul 1;192(1):117-28. doi: 10.1086/430619. Epub 2005 May 25.

Abstract

Background: Primary pyogenic liver abscess (PLA) with septic complication by Klebsiella pneumoniae is an emerging infectious disease.

Methods and results: Using DNA microarray hybridization, we identified a 20-kb chromosomal region that contained 15 open-reading frames (ORFs), including an iron-uptake system (kfu), a phosphoenolpyruvate sugar phosphotransferase system (PTS), and 6 unknown ORFs. The region was more prevalent among tissue-invasive strains (35/46) than among noninvasive strains (19/98) (P<.0001, chi2 test). To test the role played by this region in pathogenesis, 3 different deletion mutants (NTUH-K2044 [Delta kfu], K2044 [Delta ORF7-9], and K2044 [Delta PTS]) were constructed. Only the Delta kfuABC mutants showed decreased virulence in mice, compared with the wild-type strain. An in vitro assay confirmed the involvement of kfu in iron acquisition. There was a high correlation rate (85%) between the kfu/PTS region and 2 tissue invasion-associated chromosomal regions (allS and magA). Moreover, all 3 regions were present in strains that caused PLA plus endophthalmitis or meningitis.

Conclusion: Our results suggest that chromosomal heterogeneity is present in tissue-invasive K. pneumoniae strains. A genotype containing all 3 regions is strongly associated with PLA and metastatic infection. These regions may serve as convenient markers for the rapid diagnosis of emergent tissue-invasive strains.

MeSH terms

  • Animals
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Chromosome Mapping
  • Endophthalmitis / microbiology
  • Genetic Variation*
  • Genome, Bacterial
  • Humans
  • Klebsiella Infections / microbiology*
  • Klebsiella pneumoniae / genetics*
  • Klebsiella pneumoniae / pathogenicity*
  • Liver Abscess, Pyogenic / microbiology*
  • Meningitis, Bacterial / microbiology
  • Mice
  • Mice, Inbred BALB C
  • Microarray Analysis
  • Plasmids
  • Sepsis / microbiology
  • Virulence

Substances

  • Bacterial Proteins