Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1998 Jun 15;101(12):2640–2649. doi: 10.1172/JCI1823

Vaccination with a recombinant fragment of collagen adhesin provides protection against Staphylococcus aureus-mediated septic death.

I M Nilsson 1, J M Patti 1, T Bremell 1, M Höök 1, A Tarkowski 1
PMCID: PMC508854  PMID: 9637697

Abstract

Staphylococcus aureus is a major cause of nosocomial and community-acquired infections. Morbidity and mortality due to infections such as sepsis, osteomyelitis, septic arthritis, and invasive endocarditis remain high despite the use of antibiotics. The emergence of antibiotic resistant super bugs mandates that alternative strategies for the prevention and treatment of S. aureus infections are developed. We investigated the ability of vaccination with a recombinant fragment of the S. aureus collagen adhesin to protect mice against sepsis-induced death. Actively immunized NMRI mice were intravenously inoculated with the S. aureus clinical isolate strain Phillips. 14 d after inoculation, mortality in the collagen adhesin-vaccinated group was only 13%, compared with 87% in the control antigen immunized group (P < 0.001). To determine if the protective effect was antibody mediated, we passively immunized naive mice with collagen adhesin-specific antibodies. Similar to the active immunization strategy, passive transfer of collagen adhesin-specific antibodies protected mice against sepsis-induced death. In vitro experiments indicated that S. aureus opsonized with sera from collagen adhesin immunized mice promoted phagocytic uptake and enhanced intracellular killing compared with bacteria opsonized with sera from control animals. These results indicate that the collagen adhesin is a viable target in the development of immunotherapeutics against S. aureus.

Full Text

The Full Text of this article is available as a PDF (275.5 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bone R. C. Gram-positive organisms and sepsis. Arch Intern Med. 1994 Jan 10;154(1):26–34. [PubMed] [Google Scholar]
  2. Bremell T., Abdelnour A., Tarkowski A. Histopathological and serological progression of experimental Staphylococcus aureus arthritis. Infect Immun. 1992 Jul;60(7):2976–2985. doi: 10.1128/iai.60.7.2976-2985.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bremell T., Lange S., Svensson L., Jennische E., Gröndahl K., Carlsten H., Tarkowski A. Outbreak of spontaneous staphylococcal arthritis and osteitis in mice. Arthritis Rheum. 1990 Nov;33(11):1739–1744. doi: 10.1002/art.1780331120. [DOI] [PubMed] [Google Scholar]
  4. Bremell T., Lange S., Yacoub A., Rydén C., Tarkowski A. Experimental Staphylococcus aureus arthritis in mice. Infect Immun. 1991 Aug;59(8):2615–2623. doi: 10.1128/iai.59.8.2615-2623.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Flock J. I., 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. doi: 10.1002/j.1460-2075.1987.tb02511.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Foster T. J. Potential for vaccination against infections caused by Staphylococcus aureus. Vaccine. 1991 Apr;9(4):221–227. doi: 10.1016/0264-410x(91)90103-d. [DOI] [PubMed] [Google Scholar]
  7. Gillaspy A. F., Patti J. M., Smeltzer M. S. Transcriptional regulation of the Staphylococcus aureus collagen adhesion gene, cna. Infect Immun. 1997 Apr;65(4):1536–1540. doi: 10.1128/iai.65.4.1536-1540.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Greenberg D. P., Ward J. I., Bayer A. S. Influence of Staphylococcus aureus antibody on experimental endocarditis in rabbits. Infect Immun. 1987 Dec;55(12):3030–3034. doi: 10.1128/iai.55.12.3030-3034.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Helle M., Boeije L., Aarden L. A. Functional discrimination between interleukin 6 and interleukin 1. Eur J Immunol. 1988 Oct;18(10):1535–1540. doi: 10.1002/eji.1830181010. [DOI] [PubMed] [Google Scholar]
  10. Hienz S. A., Schennings T., Heimdahl A., Flock J. I. Collagen binding of Staphylococcus aureus is a virulence factor in experimental endocarditis. J Infect Dis. 1996 Jul;174(1):83–88. doi: 10.1093/infdis/174.1.83. [DOI] [PubMed] [Google Scholar]
  11. Holderbaum D., Spech T., Ehrhart L. A., Keys T., Hall G. S. Collagen binding in clinical isolates of Staphylococcus aureus. J Clin Microbiol. 1987 Dec;25(12):2258–2261. doi: 10.1128/jcm.25.12.2258-2261.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Langermann S., Palaszynski S., Barnhart M., Auguste G., Pinkner J. S., Burlein J., Barren P., Koenig S., Leath S., Jones C. H. Prevention of mucosal Escherichia coli infection by FimH-adhesin-based systemic vaccination. Science. 1997 Apr 25;276(5312):607–611. doi: 10.1126/science.276.5312.607. [DOI] [PubMed] [Google Scholar]
  13. Lee J. C. The prospects for developing a vaccine against Staphylococcus aureus. Trends Microbiol. 1996 Apr;4(4):162–166. doi: 10.1016/0966-842x(96)10021-4. [DOI] [PubMed] [Google Scholar]
  14. Lissner C. R., Swanson R. N., O'Brien A. D. Genetic control of the innate resistance of mice to Salmonella typhimurium: expression of the Ity gene in peritoneal and splenic macrophages isolated in vitro. J Immunol. 1983 Dec;131(6):3006–3013. [PubMed] [Google Scholar]
  15. Mancini G., Carbonara A. O., Heremans J. F. Immunochemical quantitation of antigens by single radial immunodiffusion. Immunochemistry. 1965 Sep;2(3):235–254. doi: 10.1016/0019-2791(65)90004-2. [DOI] [PubMed] [Google Scholar]
  16. Martin C., Saux P., Mege J. L., Perrin G., Papazian L., Gouin F. Prognostic values of serum cytokines in septic shock. Intensive Care Med. 1994;20(4):272–277. doi: 10.1007/BF01708964. [DOI] [PubMed] [Google Scholar]
  17. McDevitt D., Francois P., Vaudaux P., Foster T. J. Molecular characterization of the clumping factor (fibrinogen receptor) of Staphylococcus aureus. Mol Microbiol. 1994 Jan;11(2):237–248. doi: 10.1111/j.1365-2958.1994.tb00304.x. [DOI] [PubMed] [Google Scholar]
  18. Park P. W., Rosenbloom J., Abrams W. R., Rosenbloom J., Mecham R. P. Molecular cloning and expression of the gene for elastin-binding protein (ebpS) in Staphylococcus aureus. J Biol Chem. 1996 Jun 28;271(26):15803–15809. doi: 10.1074/jbc.271.26.15803. [DOI] [PubMed] [Google Scholar]
  19. Patti J. M., Allen B. L., McGavin M. J., Hök M. MSCRAMM-mediated adherence of microorganisms to host tissues. Annu Rev Microbiol. 1994;48:585–617. doi: 10.1146/annurev.mi.48.100194.003101. [DOI] [PubMed] [Google Scholar]
  20. Patti J. M., Boles J. O., Hök M. Identification and biochemical characterization of the ligand binding domain of the collagen adhesin from Staphylococcus aureus. Biochemistry. 1993 Oct 26;32(42):11428–11435. doi: 10.1021/bi00093a021. [DOI] [PubMed] [Google Scholar]
  21. Patti J. M., Bremell T., Krajewska-Pietrasik D., Abdelnour A., Tarkowski A., Rydén C., Hök M. The Staphylococcus aureus collagen adhesin is a virulence determinant in experimental septic arthritis. Infect Immun. 1994 Jan;62(1):152–161. doi: 10.1128/iai.62.1.152-161.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Patti J. M., House-Pompeo K., Boles J. O., Garza N., Gurusiddappa S., Hök M. Critical residues in the ligand-binding site of the Staphylococcus aureus collagen-binding adhesin (MSCRAMM). J Biol Chem. 1995 May 19;270(20):12005–12011. doi: 10.1074/jbc.270.20.12005. [DOI] [PubMed] [Google Scholar]
  23. Patti J. M., Hök M. Microbial adhesins recognizing extracellular matrix macromolecules. Curr Opin Cell Biol. 1994 Oct;6(5):752–758. doi: 10.1016/0955-0674(94)90104-x. [DOI] [PubMed] [Google Scholar]
  24. Patti J. M., Jonsson H., Guss B., Switalski L. M., Wiberg K., Lindberg M., Hök M. Molecular characterization and expression of a gene encoding a Staphylococcus aureus collagen adhesin. J Biol Chem. 1992 Mar 5;267(7):4766–4772. [PubMed] [Google Scholar]
  25. Poole-Warren L. A., Hallett M. D., Hone P. W., Burden S. H., Farrell P. C. Vaccination for prevention of CAPD associated staphylococcal infection: results of a prospective multicentre clinical trial. Clin Nephrol. 1991 May;35(5):198–206. [PubMed] [Google Scholar]
  26. Robaye B., Mosselmans R., Fiers W., Dumont J. E., Galand P. Tumor necrosis factor induces apoptosis (programmed cell death) in normal endothelial cells in vitro. Am J Pathol. 1991 Feb;138(2):447–453. [PMC free article] [PubMed] [Google Scholar]
  27. Schneewind O., Mihaylova-Petkov D., Model P. Cell wall sorting signals in surface proteins of gram-positive bacteria. EMBO J. 1993 Dec;12(12):4803–4811. doi: 10.1002/j.1460-2075.1993.tb06169.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Schuger L., Varani J., Marks R. M., Kunkel S. L., Johnson K. J., Ward P. A. Cytotoxicity of tumor necrosis factor-alpha for human umbilical vein endothelial cells. Lab Invest. 1989 Jul;61(1):62–68. [PubMed] [Google Scholar]
  29. Sirakova T., Kolattukudy P. E., Murwin D., Billy J., Leake E., Lim D., DeMaria T., Bakaletz L. Role of fimbriae expressed by nontypeable Haemophilus influenzae in pathogenesis of and protection against otitis media and relatedness of the fimbrin subunit to outer membrane protein A. Infect Immun. 1994 May;62(5):2002–2020. doi: 10.1128/iai.62.5.2002-2020.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Switalski L. M., Patti J. M., Butcher W., Gristina A. G., Speziale P., Hök M. A collagen receptor on Staphylococcus aureus strains isolated from patients with septic arthritis mediates adhesion to cartilage. Mol Microbiol. 1993 Jan;7(1):99–107. doi: 10.1111/j.1365-2958.1993.tb01101.x. [DOI] [PubMed] [Google Scholar]
  31. Vaudaux P., Pittet D., Haeberli A., Huggler E., Nydegger U. E., Lew D. P., Waldvogel F. A. Host factors selectively increase staphylococcal adherence on inserted catheters: a role for fibronectin and fibrinogen or fibrin. J Infect Dis. 1989 Nov;160(5):865–875. doi: 10.1093/infdis/160.5.865. [DOI] [PubMed] [Google Scholar]
  32. Vaudaux P., Pittet D., Haeberli A., Lerch P. G., Morgenthaler J. J., Proctor R. A., Waldvogel F. A., Lew D. P. Fibronectin is more active than fibrin or fibrinogen in promoting Staphylococcus aureus adherence to inserted intravascular catheters. J Infect Dis. 1993 Mar;167(3):633–641. doi: 10.1093/infdis/167.3.633. [DOI] [PubMed] [Google Scholar]
  33. Vercellotti G. M., McCarthy J. B., Lindholm P., Peterson P. K., Jacob H. S., Furcht L. T. Extracellular matrix proteins (fibronectin, laminin, and type IV collagen) bind and aggregate bacteria. Am J Pathol. 1985 Jul;120(1):13–21. [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES