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. 1996 Jun;64(6):2122–2129. doi: 10.1128/iai.64.6.2122-2129.1996

Identification of a fibronectin-binding protein (GfbA) in pathogenic group G streptococci.

J B Kline 1, S Xu 1, A L Bisno 1, C M Collins 1
PMCID: PMC174045  PMID: 8675316

Abstract

Attachment to eukaryotic cell surfaces is an essential step in the establishment of colonization and infection by bacterial pathogens. This report examines the adherence capabilities of pathogenic group G streptococci and demonstrates that certain group G streptococcal clinical isolates express a fibronectin-binding protein. This protein, termed GfbA for group G streptococcal fibronectin-binding protein, mediates adherence to human skin fibroblasts (HSF). The gene encoding this protein, gfbA, was isolated, and the complete DNA sequence of gfbA was determined. From this sequence GfbA was predicted to be a 580-amino-acid protein (molecular weight = 64,979) with significant amino acid identity to the group A streptococcal fibronectin-binding proteins SfbI and protein F (PrtF) (76 and 78% identity, respectively). GfbA contains regions with notable identity to the fibronectin-binding repeat domains of PrtF. gfbA(+) strains were able to bind to HSF, and preincubation of the gfbA(+) strains with fibronectin blocked this adherence. In addition, gfbA(+) strains were able to bind radiolabeled fibronectin, and this binding was inhibited with addition of excess unlabeled fibronectin. gfbA-negative strains were not able to bind either the HSF or radiolabeled fibronectin. DNA homologous to gfbA was found in 36% of the group G streptococcal isolates examined. Since not all group G streptococcal strains examined contained gfbA, this suggests there might be other tissue-specific adherence molecules expressed by these pathogenic strains.

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Selected References

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  1. Auckenthaler R., Hermans P. E., Washington J. A., 2nd Group G streptococcal bacteremia: clinical study and review of the literature. Rev Infect Dis. 1983 Mar-Apr;5(2):196–204. doi: 10.1093/clinids/5.2.196. [DOI] [PubMed] [Google Scholar]
  2. Bisno A. L., Craven D. E., McCabe W. R. M proteins of group G streptococci isolated from bacteremic human infections. Infect Immun. 1987 Mar;55(3):753–757. doi: 10.1128/iai.55.3.753-757.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Campo R. E., Schultz D. R., Bisno A. L. M proteins of group G streptococci: mechanisms of resistance to phagocytosis. J Infect Dis. 1995 Mar;171(3):601–606. doi: 10.1093/infdis/171.3.601. [DOI] [PubMed] [Google Scholar]
  4. Caparon M. G., Scott J. R. Genetic manipulation of pathogenic streptococci. Methods Enzymol. 1991;204:556–586. doi: 10.1016/0076-6879(91)04028-m. [DOI] [PubMed] [Google Scholar]
  5. Casadevall A., Freundlich L. F., Pirofski L. Septic shock caused by Pseudomonas paucimobilis. Clin Infect Dis. 1992 Mar;14(3):784–784. doi: 10.1093/clinids/14.3.784. [DOI] [PubMed] [Google Scholar]
  6. Collins C. M., Kimura A., Bisno A. L. Group G streptococcal M protein exhibits structural features analogous to those of class I M protein of group A streptococci. Infect Immun. 1992 Sep;60(9):3689–3696. doi: 10.1128/iai.60.9.3689-3696.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Courtney H. S., Li Y., Dale J. B., Hasty D. L. Cloning, sequencing, and expression of a fibronectin/fibrinogen-binding protein from group A streptococci. Infect Immun. 1994 Sep;62(9):3937–3946. doi: 10.1128/iai.62.9.3937-3946.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fischetti V. A. Streptococcal M protein: molecular design and biological behavior. Clin Microbiol Rev. 1989 Jul;2(3):285–314. doi: 10.1128/cmr.2.3.285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gnann J. W., Jr, Gray B. M., Griffin F. M., Jr, Dismukes W. E. Acute glomerulonephritis following group G streptococcal infection. J Infect Dis. 1987 Aug;156(2):411–412. doi: 10.1093/infdis/156.2.411. [DOI] [PubMed] [Google Scholar]
  11. 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. doi: 10.1073/pnas.89.13.6172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hanski E., Horwitz P. A., Caparon M. G. 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. doi: 10.1128/iai.60.12.5119-5125.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hasty D. L., Ofek I., Courtney H. S., Doyle R. J. Multiple adhesins of streptococci. Infect Immun. 1992 Jun;60(6):2147–2152. doi: 10.1128/iai.60.6.2147-2152.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Jones K. F., Fischetti V. A. Biological and immunochemical identity of M protein on group G streptococci with M protein on group A streptococci. Infect Immun. 1987 Mar;55(3):502–506. doi: 10.1128/iai.55.3.502-506.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kreikemeyer B., Talay S. R., Chhatwal G. S. Characterization of a novel fibronectin-binding surface protein in group A streptococci. Mol Microbiol. 1995 Jul;17(1):137–145. doi: 10.1111/j.1365-2958.1995.mmi_17010137.x. [DOI] [PubMed] [Google Scholar]
  16. Maniatis T., Jeffrey A., Kleid D. G. Nucleotide sequence of the rightward operator of phage lambda. Proc Natl Acad Sci U S A. 1975 Mar;72(3):1184–1188. doi: 10.1073/pnas.72.3.1184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. McCue J. D. Group G streptococcal pharyngitis. Analysis of an outbreak at a college. JAMA. 1982 Sep 17;248(11):1333–1336. doi: 10.1001/jama.248.11.1333. [DOI] [PubMed] [Google Scholar]
  18. Mosher D. F., Proctor R. A. Binding and factor XIIIa-mediated cross-linking of a 27-kilodalton fragment of fibronectin to Staphylococcus aureus. Science. 1980 Aug 22;209(4459):927–929. doi: 10.1126/science.7403857. [DOI] [PubMed] [Google Scholar]
  19. Myhre E. B., Kuusela P. Binding of human fibronectin to group A, C, and G streptococci. Infect Immun. 1983 Apr;40(1):29–34. doi: 10.1128/iai.40.1.29-34.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Natanson S., Sela S., Moses A. E., Musser J. M., Caparon M. G., Hanski E. Distribution of fibronectin-binding proteins among group A streptococci of different M types. J Infect Dis. 1995 Apr;171(4):871–878. doi: 10.1093/infdis/171.4.871. [DOI] [PubMed] [Google Scholar]
  21. Needleman S. B., Wunsch C. D. A general method applicable to the search for similarities in the amino acid sequence of two proteins. J Mol Biol. 1970 Mar;48(3):443–453. doi: 10.1016/0022-2836(70)90057-4. [DOI] [PubMed] [Google Scholar]
  22. Okada N., Liszewski M. K., Atkinson J. P., Caparon M. Membrane cofactor protein (CD46) is a keratinocyte receptor for the M protein of the group A streptococcus. Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2489–2493. doi: 10.1073/pnas.92.7.2489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Okada N., Pentland A. P., Falk P., Caparon M. G. 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. doi: 10.1172/JCI117463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Perez-Casal J., Caparon M. G., Scott J. R. Mry, a trans-acting positive regulator of the M protein gene of Streptococcus pyogenes with similarity to the receptor proteins of two-component regulatory systems. J Bacteriol. 1991 Apr;173(8):2617–2624. doi: 10.1128/jb.173.8.2617-2624.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Rakonjac J. V., Robbins J. C., Fischetti V. A. DNA sequence of the serum opacity factor of group A streptococci: identification of a fibronectin-binding repeat domain. Infect Immun. 1995 Feb;63(2):622–631. doi: 10.1128/iai.63.2.622-631.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Reed W. P., Metzler C., Albright E. Streptococcal adherence to Langerhans cells: a possible step in the pathogenesis of streptococcal pharyngitis. Clin Immunol Immunopathol. 1994 Jan;70(1):28–31. doi: 10.1006/clin.1994.1006. [DOI] [PubMed] [Google Scholar]
  27. Reuterswärd A., Miörner H., Wagner M., Kronvall G. Variations in binding of mammalian fibrinogens to streptococci groups A, B, C, E, G and to Staphylococcus aureus. Acta Pathol Microbiol Immunol Scand B. 1985 Apr;93(2):77–82. doi: 10.1111/j.1699-0463.1985.tb02855.x. [DOI] [PubMed] [Google Scholar]
  28. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Schnitzler N., Podbielski A., Baumgarten G., Mignon M., Kaufhold A. M or M-like protein gene polymorphisms in human group G streptococci. J Clin Microbiol. 1995 Feb;33(2):356–363. doi: 10.1128/jcm.33.2.356-363.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Scott J. R., Guenthner P. C., Malone L. M., Fischetti V. A. Conversion of an M- group A streptococcus to M+ by transfer of a plasmid containing an M6 gene. J Exp Med. 1986 Nov 1;164(5):1641–1651. doi: 10.1084/jem.164.5.1641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sela S., Aviv A., Tovi A., Burstein I., Caparon M. G., Hanski E. Protein F: an adhesin of Streptococcus pyogenes binds fibronectin via two distinct domains. Mol Microbiol. 1993 Dec;10(5):1049–1055. doi: 10.1111/j.1365-2958.1993.tb00975.x. [DOI] [PubMed] [Google Scholar]
  32. Simpson W. J., Robbins J. C., Cleary P. P. Evidence for group A-related M protein genes in human but not animal-associated group G streptococcal pathogens. Microb Pathog. 1987 Nov;3(5):339–350. doi: 10.1016/0882-4010(87)90004-0. [DOI] [PubMed] [Google Scholar]
  33. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  34. Switalski L. M., Ljungh A., Rydén C., Rubin K., Hök M., Wadström T. Binding of fibronectin to the surface of group A, C, and G streptococci isolated from human infections. Eur J Clin Microbiol. 1982 Dec;1(6):381–387. doi: 10.1007/BF02019939. [DOI] [PubMed] [Google Scholar]
  35. Talay S. R., Ehrenfeld E., Chhatwal G. S., Timmis K. N. Expression of the fibronectin-binding components of Streptococcus pyogenes in Escherichia coli demonstrates that they are proteins. Mol Microbiol. 1991 Jul;5(7):1727–1734. doi: 10.1111/j.1365-2958.1991.tb01921.x. [DOI] [PubMed] [Google Scholar]
  36. Talay S. R., Valentin-Weigand P., Jerlström P. G., Timmis K. N., Chhatwal G. S. 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. doi: 10.1128/iai.60.9.3837-3844.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. VanHeyningen T., Fogg G., Yates D., Hanski E., Caparon M. Adherence and fibronectin binding are environmentally regulated in the group A streptococci. Mol Microbiol. 1993 Sep;9(6):1213–1222. doi: 10.1111/j.1365-2958.1993.tb01250.x. [DOI] [PubMed] [Google Scholar]
  38. Vartian C., Lerner P. I., Shlaes D. M., Gopalakrishna K. V. Infections due to Lancefield group G streptococci. Medicine (Baltimore) 1985 Mar;64(2):75–88. doi: 10.1097/00005792-198503000-00001. [DOI] [PubMed] [Google Scholar]
  39. Wang J. R., Stinson M. W. M protein mediates streptococcal adhesion to HEp-2 cells. Infect Immun. 1994 Feb;62(2):442–448. doi: 10.1128/iai.62.2.442-448.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Yanisch-Perron C., Vieira J., Messing J. Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mp18 and pUC19 vectors. Gene. 1985;33(1):103–119. doi: 10.1016/0378-1119(85)90120-9. [DOI] [PubMed] [Google Scholar]

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