Multiple virulence factors are required for Staphylococcus aureus-induced apoptosis in endothelial cells

Cell Microbiol. 2005 Aug;7(8):1087-97. doi: 10.1111/j.1462-5822.2005.00533.x.


Staphylococcus aureus infections can result in sepsis and septic shock associated with vascular damage and multiple organ failure. Apoptosis appears to play a key role during sepsis, and the ability of S. aureus to induce apoptosis in endothelial cells might contribute to metastatic infection. In contrast to leukocytes, in human umbilical vein endothelial cells and two endothelial cell lines neither purified alpha-toxin nor staphylococcal supernatants were sufficient to induce apoptosis. Apoptosis induction instead required staphylococcal invasion as well as signals from metabolically active intracellular staphylococci. Only strongly haemolytic and invasive staphylococci, but not non-invasive strains induced apoptosis that was caspase-dependent but Fas-independent. However, only a subgroup of clinical isolates with an invasive and haemolytic phenotype induced apoptosis. Expression of alpha-toxin in a non-haemolytic strain partially restored apoptosis induction, suggesting a role of alpha-toxin as a trigger of apoptosis. Furthermore, infection of endothelial cells with isogenic mutants of various regulator genes revealed that apoptosis induction was dependent on the global regulator agr and the alternative sigma factor sigB, but not influenced by sarA. Together, our results indicate that the ability of S. aureus to induce apoptosis in endothelial cells is determined by multiple virulence factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / physiology*
  • Bacterial Proteins / metabolism
  • Caspases / metabolism
  • Cells, Cultured
  • Endothelial Cells / microbiology
  • Endothelial Cells / physiology*
  • Enzyme Activation
  • Fas Ligand Protein
  • Humans
  • Membrane Glycoproteins / physiology
  • Sigma Factor / metabolism
  • Staphylococcus aureus / isolation & purification
  • Staphylococcus aureus / metabolism
  • Staphylococcus aureus / physiology*
  • Trans-Activators / metabolism
  • Tumor Necrosis Factors / physiology
  • Type C Phospholipases / physiology
  • Type C Phospholipases / toxicity*
  • Virulence Factors / metabolism
  • Virulence Factors / physiology*


  • Agr protein, Staphylococcus aureus
  • Bacterial Proteins
  • FASLG protein, human
  • Fas Ligand Protein
  • Membrane Glycoproteins
  • SarA protein, bacterial
  • SigB protein, Bacteria
  • Sigma Factor
  • Trans-Activators
  • Tumor Necrosis Factors
  • Virulence Factors
  • Type C Phospholipases
  • Caspases