Skip to main content
NCBI home page
Infection and Immunity logoLink to Infection and Immunity
. 1997 Mar;65(3):994–1002. doi: 10.1128/iai.65.3.994-1002.1997

Immunization with FimA protects against Streptococcus parasanguis endocarditis in rats.

H B Viscount 1, C L Munro 1, D Burnette-Curley 1, D L Peterson 1, F L Macrina 1
PMCID: PMC175080  PMID: 9038308

Abstract

FimA, a surface-associated protein of Streptococcus parasanguis, is associated with initial colonization of damaged heart tissue in an endocarditis model (D. Burnette-Curley, V. Wells, H. Viscount, C. Munro, J. Fenno, P. Fives-Taylor, and F. Macrina, Infect. Immun. 63:4669-4674, 1995). We have evaluated the efficacy of recombinant FimA as a vaccine in the rat model of endocarditis and investigated in vitro the mechanism for the protective role of immunization. FimA-immunized and nonimmunized control animals were catheterized to induce heart valve damage and infected intravenously with 10(7) CFU of wild-type S. parasanguis FW213 bacteria. The presence of bacteria associated with platelet-fibrin vegetations 24 h postchallenge was evaluated. Immunized rats were significantly less susceptible to endocarditis (2 cases among 34 animals) than the control group (21 cases among 33 animals) (P < 0.001). Incubation of S. parasanguis FW213 with rabbit anti-FimA immune serum decreased the mean percent adherence (0.34% of added cells) to platelet-fibrin matrix in vitro compared with that of preimmune normal serum (5.04% of added cells; P < 0.001). Adsorption of immune serum with FimA-positive S. parasanguis FW213 yielded antiserum that failed to block adherence to the platelet-fibrin matrix. We assessed the vaccine potential of FimA as a common immunogen able to provide cross-protection in streptococcal endocarditis by determining the occurrence and expression of fimA in the viridans group streptococci and enterococci. We detected the presence of fimA homologs by Southern hybridization and PCR amplification analyses and determined by immunoblotting the expression of FimA-like proteins among a variety of streptococci and enterococci that frequently cause endocarditis. Eighty-one percent (26 of 32) of streptococcal and enterococcal strains isolated from bacteremic patients expressed proteins that comigrated with FimA and were reactive with polyclonal anti-FimA serum. Streptococcal DNA from strains that were positive by Western blot (immunoblot) analysis hybridized to the full-length fimA probe. Our studies suggest that FimA immunization results in antibody-mediated inhibition of bacterial adherence, a critical early event in the pathogenesis of endocarditis. Our data demonstrate that a majority of streptococcal strains associated with endocarditis have genes that encode FimA-like proteins. Taken together, these results suggest that FimA is a promising candidate for an endocarditis vaccine.

Full Text

The Full Text of this article is available as a PDF (849.2 KB).

Selected References

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

  1. Adler S. W., 2nd, Selinger D. S., Reed W. P. Effect of immunization on the genesis of pneumococcal endocarditis in rabbits. Infect Immun. 1981 Oct;34(1):55–61. doi: 10.1128/iai.34.1.55-61.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Archer G. L., Johnston J. L. Effect of type-specific active immunization on the development and progression of experimental Pseudomonas aeruginosa endocarditis. Infect Immun. 1979 Apr;24(1):167–173. doi: 10.1128/iai.24.1.167-173.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Burnette-Curley D., Wells V., Viscount H., Munro C. L., Fenno J. C., Fives-Taylor P., Macrina F. L. FimA, a major virulence factor associated with Streptococcus parasanguis endocarditis. Infect Immun. 1995 Dec;63(12):4669–4674. doi: 10.1128/iai.63.12.4669-4674.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dajani A. S., Bisno A. L., Chung K. J., Durack D. T., Freed M., Gerber M. A., Karchmer A. W., Millard H. D., Rahimtoola S., Shulman S. T. Prevention of bacterial endocarditis. Recommendations by the American Heart Association. JAMA. 1990 Dec 12;264(22):2919–2922. [PubMed] [Google Scholar]
  5. Delaye J., Etienne J., Feruglio G. A., Fraile J., Glauser M. P., Gruer L. D., Hagler W., Krayenbuehl H. P., Kremer R., Laird Meeter K. Prophylaxis of infective endocarditis for dental procedures. Report of a working party of the European Society of Cardiology. Eur Heart J. 1985 Oct;6(10):826–828. doi: 10.1093/oxfordjournals.eurheartj.a061767. [DOI] [PubMed] [Google Scholar]
  6. Durack D. T., Gilliland B. C., Petersdorf R. G. Effect of immunization on susceptibility to experimental Streptococcus mutans and Streptococcus sanguis endocarditis. Infect Immun. 1978 Oct;22(1):52–56. doi: 10.1128/iai.22.1.52-56.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Durack D. T. Prevention of infective endocarditis. N Engl J Med. 1995 Jan 5;332(1):38–44. doi: 10.1056/NEJM199501053320107. [DOI] [PubMed] [Google Scholar]
  8. Fenno J. C., Shaikh A., Spatafora G., Fives-Taylor P. The fimA locus of Streptococcus parasanguis encodes an ATP-binding membrane transport system. Mol Microbiol. 1995 Mar;15(5):849–863. doi: 10.1111/j.1365-2958.1995.tb02355.x. [DOI] [PubMed] [Google Scholar]
  9. Ganeshkumar N., Hannam P. M., Kolenbrander P. E., McBride B. C. Nucleotide sequence of a gene coding for a saliva-binding protein (SsaB) from Streptococcus sanguis 12 and possible role of the protein in coaggregation with actinomyces. Infect Immun. 1991 Mar;59(3):1093–1099. doi: 10.1128/iai.59.3.1093-1099.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Griffin M. R., Wilson W. R., Edwards W. D., O'Fallon W. M., Kurland L. T. Infective endocarditis. Olmsted County, Minnesota, 1950 through 1981. JAMA. 1985 Sep 6;254(9):1199–1202. doi: 10.1001/jama.254.9.1199. [DOI] [PubMed] [Google Scholar]
  12. Hogevik H., Olaison L., Andersson R., Lindberg J., Alestig K. Epidemiologic aspects of infective endocarditis in an urban population. A 5-year prospective study. Medicine (Baltimore) 1995 Nov;74(6):324–339. doi: 10.1097/00005792-199511000-00003. [DOI] [PubMed] [Google Scholar]
  13. Jenkinson H. F. Cell surface protein receptors in oral streptococci. FEMS Microbiol Lett. 1994 Aug 15;121(2):133–140. doi: 10.1111/j.1574-6968.1994.tb07089.x. [DOI] [PubMed] [Google Scholar]
  14. Kaye D., Abrutyn E. Prevention of bacterial endocarditis: 1991. Ann Intern Med. 1991 May 1;114(9):803–804. doi: 10.7326/0003-4819-114-9-803. [DOI] [PubMed] [Google Scholar]
  15. Kolenbrander P. E., Andersen R. N., Ganeshkumar N. Nucleotide sequence of the Streptococcus gordonii PK488 coaggregation adhesin gene, scaA, and ATP-binding cassette. Infect Immun. 1994 Oct;62(10):4469–4480. doi: 10.1128/iai.62.10.4469-4480.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  17. Lockhart P. B. An analysis of bacteremias during dental extractions. A double-blind, placebo-controlled study of chlorhexidine. Arch Intern Med. 1996 Mar 11;156(5):513–520. [PubMed] [Google Scholar]
  18. Lowe A. M., Lambert P. A., Smith A. W. Cloning of an Enterococcus faecalis endocarditis antigen: homology with adhesins from some oral streptococci. Infect Immun. 1995 Feb;63(2):703–706. doi: 10.1128/iai.63.2.703-706.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Munro C. L., Macrina F. L. Sucrose-derived exopolysaccharides of Streptococcus mutans V403 contribute to infectivity in endocarditis. Mol Microbiol. 1993 Apr;8(1):133–142. doi: 10.1111/j.1365-2958.1993.tb01210.x. [DOI] [PubMed] [Google Scholar]
  20. Nissen H., Nielsen P. F., Frederiksen M., Helleberg C., Nielsen J. S. Native valve infective endocarditis in the general population: a 10-year survey of the clinical picture during the 1980s. Eur Heart J. 1992 Jul;13(7):872–877. doi: 10.1093/oxfordjournals.eurheartj.a060285. [DOI] [PubMed] [Google Scholar]
  21. Oligino L., Fives-Taylor P. Overexpression and purification of a fimbria-associated adhesin of Streptococcus parasanguis. Infect Immun. 1993 Mar;61(3):1016–1022. doi: 10.1128/iai.61.3.1016-1022.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sampson J. S., O'Connor S. P., Stinson A. R., Tharpe J. A., Russell H. Cloning and nucleotide sequence analysis of psaA, the Streptococcus pneumoniae gene encoding a 37-kilodalton protein homologous to previously reported Streptococcus sp. adhesins. Infect Immun. 1994 Jan;62(1):319–324. doi: 10.1128/iai.62.1.319-324.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Scheld W. M., Calderone R. A., Brodeur J. P., Sande M. A. Influence of preformed antibody on the pathogenesis of experimental Candida albicans endocarditis. Infect Immun. 1983 Jun;40(3):950–955. doi: 10.1128/iai.40.3.950-955.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Scheld W. M., Thomas J. H., Sande M. A. Influence of preformed antibody on experimental Streptococcus sanguis endocarditis. Infect Immun. 1979 Sep;25(3):781–785. doi: 10.1128/iai.25.3.781-785.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Schennings T., Heimdahl A., Coster K., Flock J. I. Immunization with fibronectin binding protein from Staphylococcus aureus protects against experimental endocarditis in rats. Microb Pathog. 1993 Sep;15(3):227–236. doi: 10.1006/mpat.1993.1073. [DOI] [PubMed] [Google Scholar]
  26. Schroeder V. A., Michalek S. M., Macrina F. L. Biochemical characterization and evaluation of virulence of a fructosyltransferase-deficient mutant of Streptococcus mutans V403. Infect Immun. 1989 Nov;57(11):3560–3569. doi: 10.1128/iai.57.11.3560-3569.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Simmons N. A., Ball A. P., Cawson R. A., Eykyn S. J., Littler W. A., McGowan D. A., Oakley C. M., Shanson D. C. Antibiotic prophylaxis and infective endocarditis. Lancet. 1992 May 23;339(8804):1292–1293. doi: 10.1016/0140-6736(92)91618-i. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. Takeda S., Pier G. B., Kojima Y., Tojo M., Muller E., Tosteson T., Goldmann D. A. Protection against endocarditis due to Staphylococcus epidermidis by immunization with capsular polysaccharide/adhesin. Circulation. 1991 Dec;84(6):2539–2546. doi: 10.1161/01.cir.84.6.2539. [DOI] [PubMed] [Google Scholar]
  30. van de Rijn I. Role of culture conditions and immunization in experimental nutritionally variant streptococcal endocarditis. Infect Immun. 1985 Dec;50(3):641–646. doi: 10.1128/iai.50.3.641-646.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. van der Meer J. T., Thompson J., Valkenburg H. A., Michel M. F. Epidemiology of bacterial endocarditis in The Netherlands. I. Patient characteristics. Arch Intern Med. 1992 Sep;152(9):1863–1868. doi: 10.1001/archinte.152.9.1863. [DOI] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES