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. 1995 Dec;63(12):4738–4743. doi: 10.1128/iai.63.12.4738-4743.1995

Role of Staphylococcus aureus coagulase and clumping factor in pathogenesis of experimental endocarditis.

P Moreillon 1, J M Entenza 1, P Francioli 1, D McDevitt 1, T J Foster 1, P François 1, P Vaudaux 1
PMCID: PMC173679  PMID: 7591130

Abstract

The pathogenic role of staphylococcal coagulase and clumping factor was investigated in the rat model of endocarditis. The coagulase-producing and clumping factor-producing parent strain Staphylococcus aureus Newman and a series of mutants defective in either coagulase, clumping factor, or both were tested for their ability (i) to attach in vitro to either rat fibrinogen or platelet-fibrin clots and (ii) to produce endocarditis in rats with catheter-induced aortic vegetations. In vitro, the clumping factor-defective mutants were up to 100 times less able than the wild type strain to attach to fibrinogen and also significantly less adherent than the parents to platelet-fibrin clots. Coagulase-defective mutants, in contrast, were not altered in their in vitro adherence phenotype. The rate of in vivo infection was inoculum dependent. Clumping factor-defective mutants produced ca. 50% less endocarditis than the parent organisms when injected at inoculum sizes infecting, respectively, 40 and 80% (ID40 and ID80, respectively) of rats with the wild-type strain. This was a trend at the ID40 but was statistically significant at the ID80 (P < 0.05). Coagulase-defective bacteria were not affected in their infectivity. Complementation of a clumping factor-defective mutant with a copy of the wild-type clumping factor gene restored both its in vitro adherence and its in vivo infectivity. These results show that clumping factor plays a specific role in the pathogenesis of S. aureus endocarditis. Nevertheless, the rate of endocarditis with clumping factor-defective mutants increased with larger inocula, indicating the contribution of additional pathogenic determinants in the infective process.

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Selected References

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  1. ANGRIST A. A., OKA M. Pathogenesis of bacterial endocarditis. JAMA. 1963 Jan 26;183:249–252. doi: 10.1001/jama.1963.63700040009010b. [DOI] [PubMed] [Google Scholar]
  2. Baddour L. M., Tayidi M. M., Walker E., McDevitt D., Foster T. J. Virulence of coagulase-deficient mutants of Staphylococcus aureus in experimental endocarditis. J Med Microbiol. 1994 Oct;41(4):259–263. doi: 10.1099/00222615-41-4-259. [DOI] [PubMed] [Google Scholar]
  3. Baddour L. M. Virulence factors among gram-positive bacteria in experimental endocarditis. Infect Immun. 1994 Jun;62(6):2143–2148. doi: 10.1128/iai.62.6.2143-2148.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bayer A. S., Sullam P. M., Ramos M., Li C., Cheung A. L., Yeaman M. R. Staphylococcus aureus induces platelet aggregation via a fibrinogen-dependent mechanism which is independent of principal platelet glycoprotein IIb/IIIa fibrinogen-binding domains. Infect Immun. 1995 Sep;63(9):3634–3641. doi: 10.1128/iai.63.9.3634-3641.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bodén M. K., Flock J. I. Fibrinogen-binding protein/clumping factor from Staphylococcus aureus. Infect Immun. 1989 Aug;57(8):2358–2363. doi: 10.1128/iai.57.8.2358-2363.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cheung A. I., Projan S. J., Edelstein R. E., Fischetti V. A. Cloning, expression, and nucleotide sequence of a Staphylococcus aureus gene (fbpA) encoding a fibrinogen-binding protein. Infect Immun. 1995 May;63(5):1914–1920. doi: 10.1128/iai.63.5.1914-1920.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cheung A. L., Eberhardt K. J., Chung E., Yeaman M. R., Sullam P. M., Ramos M., Bayer A. S. Diminished virulence of a sar-/agr- mutant of Staphylococcus aureus in the rabbit model of endocarditis. J Clin Invest. 1994 Nov;94(5):1815–1822. doi: 10.1172/JCI117530. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cheung A. L., Koomey J. M., Butler C. A., Projan S. J., Fischetti V. A. Regulation of exoprotein expression in Staphylococcus aureus by a locus (sar) distinct from agr. Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6462–6466. doi: 10.1073/pnas.89.14.6462. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cheung A. L., Yeaman M. R., Sullam P. M., Witt M. D., Bayer A. S. Role of the sar locus of Staphylococcus aureus in induction of endocarditis in rabbits. Infect Immun. 1994 May;62(5):1719–1725. doi: 10.1128/iai.62.5.1719-1725.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Chow J. W., Thal L. A., Perri M. B., Vazquez J. A., Donabedian S. M., Clewell D. B., Zervos M. J. Plasmid-associated hemolysin and aggregation substance production contribute to virulence in experimental enterococcal endocarditis. Antimicrob Agents Chemother. 1993 Nov;37(11):2474–2477. doi: 10.1128/aac.37.11.2474. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Crawford I., Russell C. Comparative adhesion of seven species of streptococci isolated from the blood of patients with sub-acute bacterial endocarditis to fibrin-platelet clots in vitro. J Appl Bacteriol. 1986 Feb;60(2):127–133. doi: 10.1111/j.1365-2672.1986.tb03369.x. [DOI] [PubMed] [Google Scholar]
  12. DUTHIE E. S., LORENZ L. L. Staphylococcal coagulase; mode of action and antigenicity. J Gen Microbiol. 1952 Feb;6(1-2):95–107. doi: 10.1099/00221287-6-1-2-95. [DOI] [PubMed] [Google Scholar]
  13. Dickinson R. B., Nagel J. A., McDevitt D., Foster T. J., Proctor R. A., Cooper S. L. Quantitative comparison of clumping factor- and coagulase-mediated Staphylococcus aureus adhesion to surface-bound fibrinogen under flow. Infect Immun. 1995 Aug;63(8):3143–3150. doi: 10.1128/iai.63.8.3143-3150.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gould K., Ramirez-Ronda C. H., Holmes R. K., Sanford J. P. Adherence of bacteria to heart valves in vitro. J Clin Invest. 1975 Dec;56(6):1364–1370. doi: 10.1172/JCI108216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hamill R. J. Role of fibronectin in infective endocarditis. Rev Infect Dis. 1987 Jul-Aug;9 (Suppl 4):S360–S371. doi: 10.1093/clinids/9.supplement_4.s360. [DOI] [PubMed] [Google Scholar]
  16. Herzberg M. C., MacFarlane G. D., Gong K., Armstrong N. N., Witt A. R., Erickson P. R., Meyer M. W. The platelet interactivity phenotype of Streptococcus sanguis influences the course of experimental endocarditis. Infect Immun. 1992 Nov;60(11):4809–4818. doi: 10.1128/iai.60.11.4809-4818.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Héraïef E., Glauser M. P., Freedman L. R. Natural history of aortic valve endocarditis in rats. Infect Immun. 1982 Jul;37(1):127–131. doi: 10.1128/iai.37.1.127-131.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kuypers J. M., Proctor R. A. Reduced adherence to traumatized rat heart valves by a low-fibronectin-binding mutant of Staphylococcus aureus. Infect Immun. 1989 Aug;57(8):2306–2312. doi: 10.1128/iai.57.8.2306-2312.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lee C. Y., Buranen S. L., Ye Z. H. Construction of single-copy integration vectors for Staphylococcus aureus. Gene. 1991 Jul 15;103(1):101–105. doi: 10.1016/0378-1119(91)90399-v. [DOI] [PubMed] [Google Scholar]
  20. Lowrance J. H., Baddour L. M., Simpson W. A. The role of fibronectin binding in the rat model of experimental endocarditis caused by Streptococcus sanguis. J Clin Invest. 1990 Jul;86(1):7–13. doi: 10.1172/JCI114717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lowy F. D., Chang D. S., Neuhaus E. G., Horne D. S., Tomasz A., Steigbigel N. H. Effect of penicillin on the adherence of Streptococcus sanguis in vitro and in the rabbit model of endocarditis. J Clin Invest. 1983 Mar;71(3):668–675. doi: 10.1172/JCI110813. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. McDevitt D., Vaudaux P., Foster T. J. Genetic evidence that bound coagulase of Staphylococcus aureus is not clumping factor. Infect Immun. 1992 Apr;60(4):1514–1523. doi: 10.1128/iai.60.4.1514-1523.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Moreillon P., Overholser C. D., Malinverni R., Bille J., Glauser M. P. Predictors of endocarditis in isolates from cultures of blood following dental extractions in rats with periodontal disease. J Infect Dis. 1988 May;157(5):990–995. doi: 10.1093/infdis/157.5.990. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Phonimdaeng P., O'Reilly M., Nowlan P., Bramley A. J., Foster T. J. The coagulase of Staphylococcus aureus 8325-4. Sequence analysis and virulence of site-specific coagulase-deficient mutants. Mol Microbiol. 1990 Mar;4(3):393–404. doi: 10.1111/j.1365-2958.1990.tb00606.x. [DOI] [PubMed] [Google Scholar]
  27. Scheld W. M., Valone J. A., Sande M. A. Bacterial adherence in the pathogenesis of endocarditis. Interaction of bacterial dextran, platelets, and fibrin. J Clin Invest. 1978 May;61(5):1394–1404. doi: 10.1172/JCI109057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Tamura G. S., Rubens C. E. Group B streptococci adhere to a variant of fibronectin attached to a solid phase. Mol Microbiol. 1995 Feb;15(3):581–589. doi: 10.1111/j.1365-2958.1995.tb02271.x. [DOI] [PubMed] [Google Scholar]
  29. Vaudaux P. E., François P., Proctor R. A., McDevitt D., Foster T. J., Albrecht R. M., Lew D. P., Wabers H., Cooper S. L. Use of adhesion-defective mutants of Staphylococcus aureus to define the role of specific plasma proteins in promoting bacterial adhesion to canine arteriovenous shunts. Infect Immun. 1995 Feb;63(2):585–590. doi: 10.1128/iai.63.2.585-590.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Vaudaux P. E., Waldvogel F. A., Morgenthaler J. J., Nydegger U. E. Adsorption of fibronectin onto polymethylmethacrylate and promotion of Staphylococcus aureus adherence. Infect Immun. 1984 Sep;45(3):768–774. doi: 10.1128/iai.45.3.768-774.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]

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