Correlation of Klebsiella pneumoniae comparative genetic analyses with virulence profiles in a murine respiratory disease model

PLoS One. 2014 Sep 9;9(9):e107394. doi: 10.1371/journal.pone.0107394. eCollection 2014.

Abstract

Klebsiella pneumoniae is a bacterial pathogen of worldwide importance and a significant contributor to multiple disease presentations associated with both nosocomial and community acquired disease. ATCC 43816 is a well-studied K. pneumoniae strain which is capable of causing an acute respiratory disease in surrogate animal models. In this study, we performed sequencing of the ATCC 43816 genome to support future efforts characterizing genetic elements required for disease. Furthermore, we performed comparative genetic analyses to the previously sequenced genomes from NTUH-K2044 and MGH 78578 to gain an understanding of the conservation of known virulence determinants amongst the three strains. We found that ATCC 43816 and NTUH-K2044 both possess the known virulence determinant for yersiniabactin, as well as a Type 4 secretion system (T4SS), CRISPR system, and an acetonin catabolism locus, all absent from MGH 78578. While both NTUH-K2044 and MGH 78578 are clinical isolates, little is known about the disease potential of these strains in cell culture and animal models. Thus, we also performed functional analyses in the murine macrophage cell lines RAW264.7 and J774A.1 and found that MGH 78578 (K52 serotype) was internalized at higher levels than ATCC 43816 (K2) and NTUH-K2044 (K1), consistent with previous characterization of the antiphagocytic properties of K1 and K2 serotype capsules. We also examined the three K. pneumoniae strains in a novel BALB/c respiratory disease model and found that ATCC 43816 and NTUH-K2044 are highly virulent (LD50<100 CFU) while MGH 78578 is relatively avirulent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / genetics
  • Base Sequence
  • Cell Line
  • DNA, Bacterial / genetics
  • Disease Models, Animal
  • Genome, Bacterial / genetics
  • Klebsiella Infections / microbiology*
  • Klebsiella pneumoniae / genetics*
  • Macrophages / microbiology
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Respiratory Tract Diseases / microbiology*
  • Sequence Analysis, DNA / methods
  • Virulence / genetics*
  • Virulence Factors / genetics*

Substances

  • Bacterial Proteins
  • DNA, Bacterial
  • Virulence Factors

Grant support

This work was supported by internal funding at the University of Louisville. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.