Cytotoxic effects of Kingella kingae outer membrane vesicles on human cells

Microb Pathog. Jul-Aug 2011;51(1-2):22-30. doi: 10.1016/j.micpath.2011.03.005. Epub 2011 Apr 2.

Abstract

Kingella kingae is an emerging pathogen causing osteoarticular infections in pediatric patients. Electron microscopy of K. kingae clinical isolates revealed the heterogeneously-sized membranous structures blebbing from the outer membrane that were classified as outer membrane vesicles (OMVs). OMVs purified from the secreted fraction of a septic arthritis K. kingae isolate were characterized. Among several major proteins, K. kingae OMVs contained virulence factors RtxA toxin and PilC2 pilus adhesin. RtxA was also found secreted as a soluble protein in the extracellular environment indicating that the bacterium may utilize different mechanisms for the toxin delivery. OMVs were shown to be hemolytic and possess some leukotoxic activity while high leukotoxicity was detected in the non-hemolytic OMV-free component of the secreted fraction. OMVs were internalized by human osteoblasts and synovial cells. Upon interaction with OMVs, the cells produced increased levels of human granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 6 (IL-6) suggesting that these cytokines might be involved in the signaling response of infected joint and bone tissues during natural K. kingae infection. This study is the first report of OMV production by K. kingae and demonstrates that OMVs are a complex virulence factor of the organism causing cytolytic and inflammatory effects on host cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Infectious / microbiology
  • Bacterial Outer Membrane Proteins / metabolism
  • Bacterial Outer Membrane Proteins / toxicity*
  • Bacterial Toxins / metabolism
  • Bacterial Toxins / pharmacology
  • Cell Membrane / chemistry
  • Cell Membrane / ultrastructure*
  • Child
  • Cytokines / metabolism
  • Fimbriae Proteins / metabolism
  • Fimbriae Proteins / pharmacology
  • Humans
  • Kingella kingae / isolation & purification
  • Kingella kingae / pathogenicity*
  • Kingella kingae / ultrastructure
  • Mice
  • Osteoblasts / cytology
  • Osteoblasts / immunology
  • Osteoblasts / pathology*
  • Synovial Fluid / cytology*
  • Synovial Fluid / drug effects
  • Synovial Fluid / immunology
  • Virulence Factors / immunology
  • Virulence Factors / metabolism
  • Virulence Factors / toxicity*

Substances

  • Bacterial Outer Membrane Proteins
  • Bacterial Toxins
  • Cytokines
  • Virulence Factors
  • Fimbriae Proteins