Staphylococcus aureus recruits Cdc42GAP through recycling endosomes and the exocyst to invade human endothelial cells

J Cell Sci. 2016 Aug 1;129(15):2937-49. doi: 10.1242/jcs.186213. Epub 2016 Jun 16.


Activation and invasion of the vascular endothelium by Staphylococcus aureus is a major cause of sepsis and endocarditis. For endothelial cell invasion, S. aureus triggers actin polymerization through Cdc42, N-WASp (also known as WASL) and the Arp2/3 complex to assemble a phagocytic cup-like structure. Here, we show that after stimulating actin polymerization staphylococci recruit Cdc42GAP (also known as ARHGAP1) which deactivates Cdc42 and terminates actin polymerization in the phagocytic cups. Cdc42GAP is delivered to the invading bacteria on recycling endocytic vesicles in concert with the exocyst complex. When Cdc42GAP recruitment by staphylococci was prevented by blocking recycling endocytic vesicles or the exocyst complex, or when Cdc42 was constitutively activated, phagocytic cup closure was impaired and endothelial cell invasion was inhibited. Thus, to complete invasion of the endothelium, staphylococci reorient recycling endocytic vesicles to recruit Cdc42GAP, which terminates Cdc42-induced actin polymerization in phagocytic cups. Analogous mechanisms might govern other Cdc42-dependent cell functions.

Keywords: Cdc42GAP; Endothelium; Phagocytosis; Recycling endosomes; Staphylococci.

Publication types

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

MeSH terms

  • Actins / metabolism
  • Bacterial Proteins / metabolism
  • Endocytosis*
  • Endosomes / metabolism*
  • GTPase-Activating Proteins / metabolism*
  • Gene Knockdown Techniques
  • Human Umbilical Vein Endothelial Cells / metabolism*
  • Human Umbilical Vein Endothelial Cells / microbiology*
  • Humans
  • Phagocytosis
  • Polymerization
  • Staphylococcus aureus / physiology*
  • Vesicular Transport Proteins / metabolism*
  • cdc42 GTP-Binding Protein / metabolism


  • ARHGAP1 protein, human
  • Actins
  • Bacterial Proteins
  • GTPase-Activating Proteins
  • Vesicular Transport Proteins
  • cdc42 GTP-Binding Protein