Roles of integrins and fibronectin in the entry of Streptococcus pyogenes into cells via protein F1

Mol Microbiol. 1998 Nov;30(3):625-37. doi: 10.1046/j.1365-2958.1998.01097.x.


Entry of group A streptococcus (GAS) into cells has been suggested as an important trait in GAS pathogenicity. Protein F1, a fibronectin (Fn) binding protein, mediates GAS adherence to cells and the extracellular matrix, and efficient cell internalization. We demonstrate that the cellular receptors responsible for protein F1-mediated internalization of GAS are integrins capable of Fn binding. In HeLa cells, bacterial entry is blocked by anti-beta1 integrin monoclonal antibody. In the mouse cell line GD25, a beta1 null mutant, the alphavbeta3 integrin promotes GAS entry. Internalization of these cells by GAS is blocked by a peptide that specifically binds to alphavbeta3 integrin. In both cell lines, entry of GAS requires the occupancy of protein F1 by Fn. Neither the 29 kDa nor the 70 kDa N-terminal fragments or the 120 kDa cell-binding fragment of Fn promote bacterial entry. Fn-coated beads are taken up efficiently by HeLa cells. Both the entry of GAS via protein F1 and the uptake of Fn-coated beads are blocked by anti-beta1 antibody but are unaffected by a large excess of soluble Fn. Internalization of HeLa cells by bacteria bearing increasing amounts of prebound Fn to protein F1 reveals a sigmoidal ultrasensitive curve. These suggest that the ability of particles to interact via Fn with multiple integrin sites plays a central role in their ability to enter cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adhesins, Bacterial / physiology*
  • Antibodies, Monoclonal / pharmacology
  • Bacterial Proteins / physiology
  • Endocytosis / physiology
  • Fibronectins / physiology*
  • Fluorescent Antibody Technique
  • HeLa Cells
  • Humans
  • Integrins / physiology*
  • Microscopy, Fluorescence
  • Microspheres
  • Protein Binding / physiology
  • Receptors, Cell Surface / metabolism
  • Streptococcus pyogenes / pathogenicity*


  • Adhesins, Bacterial
  • Antibodies, Monoclonal
  • Bacterial Proteins
  • Fibronectins
  • Integrins
  • Receptors, Cell Surface
  • fibronectin-binding proteins, bacterial