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Infect Immun. Apr 1997; 65(4): 1357–1363.
PMCID: PMC175140

The fibronectin-binding protein of Streptococcus pyogenes, SfbI, is involved in the internalization of group A streptococci by epithelial cells.


Streptococcus pyogenes organisms (group A streptococci) are considered to be highly adhesive extracellular pathogens. However, it has recently been reported that S. pyogenes has the capacity to efficiently invade eukaryotic cells. In this study, we demonstrate that the interaction of S. pyogenes fibronectin-binding protein (SfbI) with fibronectin on nonphagocytic HEp-2 cells triggers bacterial internalization. Blocking of the SfbI adhesin by either antibodies against the whole protein or antibodies against the fibronectin-binding domains of SfbI, as well as pretreatment of HEp-2 cells with purified SfbI protein, prevents both S. pyogenes attachment and internalization. Inert latex beads precoated with the purified SfbI protein are ingested by eukaryotic cells, demonstrating that SfbI is per se enough to trigger the internalization process. Experiments performed with a recombinant SfbI domain encompassing the two fibronectin-binding regions of the SfbI molecule demonstrated that these binding regions are essential and sufficient to activate uptake by HEp-2 cells. These results demonstrate that the fibronectin-binding protein SfbI is involved in both S. pyogenes' attachment to and ingestion by HEp-2 cells and contribute to elucidation of the underlying molecular events leading to eukaryotic cell invasion by S. pyogenes.

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Selected References

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  • Beachey EH. Bacterial adherence: adhesin-receptor interactions mediating the attachment of bacteria to mucosal surface. J Infect Dis. 1981 Mar;143(3):325–345. [PubMed]
  • Bisno AL. Group A streptococcal infections and acute rheumatic fever. N Engl J Med. 1991 Sep 12;325(11):783–793. [PubMed]
  • Courtney HS, von Hunolstein C, Dale JB, Bronze MS, Beachey EH, Hasty DL. Lipoteichoic acid and M protein: dual adhesins of group A streptococci. Microb Pathog. 1992 Mar;12(3):199–208. [PubMed]
  • Courtney HS, Dale JB, Hasty DI. Differential effects of the streptococcal fibronectin-binding protein, FBP54, on adhesion of group A streptococci to human buccal cells and HEp-2 tissue culture cells. Infect Immun. 1996 Jul;64(7):2415–2419. [PMC free article] [PubMed]
  • Finlay BB, Falkow S. Comparison of the invasion strategies used by Salmonella cholerae-suis, Shigella flexneri and Yersinia enterocolitica to enter cultured animal cells: endosome acidification is not required for bacterial invasion or intracellular replication. Biochimie. 1988 Aug;70(8):1089–1099. [PubMed]
  • Flock JI, Fröman G, Jönsson K, Guss B, Signäs C, Nilsson B, Raucci G, Hök M, Wadström T, Lindberg M. Cloning and expression of the gene for a fibronectin-binding protein from Staphylococcus aureus. EMBO J. 1987 Aug;6(8):2351–2357. [PMC free article] [PubMed]
  • Guzmàn CA, Pruzzo C, LiPira G, Calegari L. Role of adherence in pathogenesis of Enterococcus faecalis urinary tract infection and endocarditis. Infect Immun. 1989 Jun;57(6):1834–1838. [PMC free article] [PubMed]
  • Guzman CA, Rohde M, Bock M, Timmis KN. Invasion and intracellular survival of Bordetella bronchiseptica in mouse dendritic cells. Infect Immun. 1994 Dec;62(12):5528–5537. [PMC free article] [PubMed]
  • Hanski E, Caparon M. Protein F, a fibronectin-binding protein, is an adhesin of the group A streptococcus Streptococcus pyogenes. Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):6172–6176. [PMC free article] [PubMed]
  • Hanski E, Horwitz PA, Caparon MG. Expression of protein F, the fibronectin-binding protein of Streptococcus pyogenes JRS4, in heterologous streptococcal and enterococcal strains promotes their adherence to respiratory epithelial cells. Infect Immun. 1992 Dec;60(12):5119–5125. [PMC free article] [PubMed]
  • Hynes RO. Integrins: a family of cell surface receptors. Cell. 1987 Feb 27;48(4):549–554. [PubMed]
  • Isberg RR, Leong JM. Multiple beta 1 chain integrins are receptors for invasin, a protein that promotes bacterial penetration into mammalian cells. Cell. 1990 Mar 9;60(5):861–871. [PubMed]
  • Kaplan EL. The resurgence of group A streptococcal infections and their sequelae. Eur J Clin Microbiol Infect Dis. 1991 Feb;10(2):55–57. [PubMed]
  • Kline JB, Xu S, Bisno AL, Collins CM. Identification of a fibronectin-binding protein (GfbA) in pathogenic group G streptococci. Infect Immun. 1996 Jun;64(6):2122–2129. [PMC free article] [PubMed]
  • Kuroda K, Brown EJ, Telle WB, Russell DG, Ratliff TL. Characterization of the internalization of bacillus Calmette-Guerin by human bladder tumor cells. J Clin Invest. 1993 Jan;91(1):69–76. [PMC free article] [PubMed]
  • LaPenta D, Rubens C, Chi E, Cleary PP. Group A streptococci efficiently invade human respiratory epithelial cells. Proc Natl Acad Sci U S A. 1994 Dec 6;91(25):12115–12119. [PMC free article] [PubMed]
  • Okada N, Pentland AP, Falk P, Caparon MG. M protein and protein F act as important determinants of cell-specific tropism of Streptococcus pyogenes in skin tissue. J Clin Invest. 1994 Sep;94(3):965–977. [PMC free article] [PubMed]
  • Olsén A, Jonsson A, Normark S. Fibronectin binding mediated by a novel class of surface organelles on Escherichia coli. Nature. 1989 Apr 20;338(6217):652–655. [PubMed]
  • Rubens CE, Smith S, Hulse M, Chi EY, van Belle G. Respiratory epithelial cell invasion by group B streptococci. Infect Immun. 1992 Dec;60(12):5157–5163. [PMC free article] [PubMed]
  • Schorey JS, Li Q, McCourt DW, Bong-Mastek M, Clark-Curtiss JE, Ratliff TL, Brown EJ. A Mycobacterium leprae gene encoding a fibronectin binding protein is used for efficient invasion of epithelial cells and Schwann cells. Infect Immun. 1995 Jul;63(7):2652–2657. [PMC free article] [PubMed]
  • Simpson WA, Beachey EH. Adherence of group A streptococci to fibronectin on oral epithelial cells. Infect Immun. 1983 Jan;39(1):275–279. [PMC free article] [PubMed]
  • Simpson WA, Courtney HS, Ofek I. Interactions of fibronectin with streptococci: the role of fibronectin as a receptor for Streptococcus pyogenes. Rev Infect Dis. 1987 Jul-Aug;9 (Suppl 4):S351–S359. [PubMed]
  • Talay SR, Valentin-Weigand P, Jerlström PG, Timmis KN, Chhatwal GS. Fibronectin-binding protein of Streptococcus pyogenes: sequence of the binding domain involved in adherence of streptococci to epithelial cells. Infect Immun. 1992 Sep;60(9):3837–3844. [PMC free article] [PubMed]
  • Talay SR, Valentin-Weigand P, Timmis KN, Chhatwal GS. Domain structure and conserved epitopes of Sfb protein, the fibronectin-binding adhesin of Streptococcus pyogenes. Mol Microbiol. 1994 Aug;13(3):531–539. [PubMed]
  • Talay SR, Grammel MP, Chhatwal GS. Structure of a group C streptococcal protein that binds to fibrinogen, albumin and immunoglobulin G via overlapping modules. Biochem J. 1996 Apr 15;315(Pt 2):577–582. [PMC free article] [PubMed]
  • Toye B, Zhong GM, Peeling R, Brunham RC. Immunologic characterization of a cloned fragment containing the species-specific epitope from the major outer membrane protein of Chlamydia trachomatis. Infect Immun. 1990 Dec;58(12):3909–3913. [PMC free article] [PubMed]
  • Valentin-Weigand P, Talay SR, Kaufhold A, Timmis KN, Chhatwal GS. The fibronectin binding domain of the Sfb protein adhesin of Streptococcus pyogenes occurs in many group A streptococci and does not cross-react with heart myosin. Microb Pathog. 1994 Aug;17(2):111–120. [PubMed]
  • Van de Water L, Destree AT, Hynes RO. Fibronectin binds to some bacteria but does not promote their uptake by phagocytic cells. Science. 1983 Apr 8;220(4593):201–204. [PubMed]
  • Wang JR, Stinson MW. M protein mediates streptococcal adhesion to HEp-2 cells. Infect Immun. 1994 Feb;62(2):442–448. [PMC free article] [PubMed]
  • Young VB, Falkow S, Schoolnik GK. The invasin protein of Yersinia enterocolitica: internalization of invasin-bearing bacteria by eukaryotic cells is associated with reorganization of the cytoskeleton. J Cell Biol. 1992 Jan;116(1):197–207. [PMC free article] [PubMed]

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