High-frequency invasion of epithelial cells by Streptococcus pyogenes can be activated by fibrinogen and peptides containing the sequence RGD

Abstract

The ability of Streptococcus pyogenes to invade human epithelial cells has been suggested to be an important contributing factor to the bacterium's ability to cause severe, invasive infections. We know little, however, of the mechanism underlying intracellular invasion by this organism. In this study, we demonstrate that the invasion of cultured human epithelial cells by a serotype M1 strain of S. pyogenes (strain 90-226) is stimulated over 50-fold by the addition of fetal calf serum (FCS) to the cell culture medium (RPMI medium). Purified human fibrinogen and peptides containing the sequence Arg-Gly-Asp (RGD) were also found to promote bacterial invasion of cultured cells. Experiments that demonstrate that the agonists stimulate invasion by interacting with bacterial cells are described. Invasion stimulation did not appear to involve de novo synthesis of a bacterial protein, as FCS and fibrinogen stimulated invasion in the presence of chloramphenicol. Although the agonists stimulated adherence by up to threefold, strain 90-226 efficiently adhered to cultured cells in unsupplemented RPMI medium. The invasion index (the number of internalized CFU/the number of adherent CFU) of strain 90-226 was increased 10- to 25-fold by the addition of the agonists. Postinternalization survival of bacteria was unaffected by fibrinogen or FCS. Thus, the agonistic factors affect the efficiency by which adherent bacteria are internalized by epithelial cells.