Acinetobacter baumannii secretes cytotoxic outer membrane protein A via outer membrane vesicles

PLoS One. 2011 Feb 28;6(2):e17027. doi: 10.1371/journal.pone.0017027.

Abstract

Acinetobacter baumannii is an important nosocomial pathogen that causes a high morbidity and mortality rate in infected patients, but pathogenic mechanisms of this microorganism regarding the secretion and delivery of virulence factors to host cells have not been characterized. Gram-negative bacteria naturally secrete outer membrane vesicles (OMVs) that play a role in the delivery of virulence factors to host cells. A. baumannii has been shown to secrete OMVs when cultured in vitro, but the role of OMVs in A. baumannii pathogenesis is not well elucidated. In the present study, we evaluated the secretion and delivery of virulence factors of A. baumannii to host cells via the OMVs and assessed the cytotoxic activity of outer membrane protein A (AbOmpA) packaged in the OMVs. A. baumannii ATCC 19606(T) secreted OMVs during in vivo infection as well as in vitro cultures. Potential virulence factors, including AbOmpA and tissue-degrading enzymes, were associated with A. baumannii OMVs. A. baumannii OMVs interacted with lipid rafts in the plasma membranes and then delivered virulence factors to host cells. The OMVs from A. baumannii ATCC 19606(T) induced apoptosis of host cells, whereas this effect was not detected in the OMVs from the ΔompA mutant, thereby reflecting AbOmpA-dependent host cell death. The N-terminal region of AbOmpA(22-170) was responsible for host cell death. In conclusion, the OMV-mediated delivery of virulence factors to host cells may well contribute to pathogenesis during A. baumannii infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acinetobacter Infections / metabolism
  • Acinetobacter Infections / microbiology
  • Acinetobacter Infections / pathology
  • Acinetobacter baumannii / metabolism*
  • Acinetobacter baumannii / pathogenicity
  • Acinetobacter baumannii / physiology
  • Acinetobacter baumannii / ultrastructure
  • Bacterial Outer Membrane Proteins / chemistry
  • Bacterial Outer Membrane Proteins / metabolism
  • Cell Wall / metabolism
  • Cell Wall / physiology*
  • Cells, Cultured
  • HeLa Cells
  • Host-Pathogen Interactions / physiology
  • Humans
  • Protein Structure, Tertiary / physiology
  • Secretory Vesicles / metabolism*
  • Staphylococcal Protein A / chemistry
  • Staphylococcal Protein A / metabolism*
  • U937 Cells
  • Virulence Factors / chemistry
  • Virulence Factors / metabolism

Substances

  • Bacterial Outer Membrane Proteins
  • Staphylococcal Protein A
  • Virulence Factors