Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1994 May;62(5):1719–1725. doi: 10.1128/iai.62.5.1719-1725.1994

Role of the sar locus of Staphylococcus aureus in induction of endocarditis in rabbits.

A L Cheung 1, M R Yeaman 1, P M Sullam 1, M D Witt 1, A S Bayer 1
PMCID: PMC186392  PMID: 8168933

Abstract

A regulatory locus on the Staphylococcus aureus chromosome, designated sar, is involved in the expression of cell wall proteins, some of which are potentially important in the pathogenesis of endocarditis. For instance, mutant 11D2 (sar::Tn917LTV1) was found to bind substantially less to matrix proteins (i.e., fibrinogen and fibronectin) than parent strain DB. Remarkably, these two strains did not differ in other phenotypes considered important in the initiation of endocarditis (e.g., binding to platelets and resistance to platelet-derived microbicidal proteins). The isogenic pair were compared for pathogenicity in a rabbit endocarditis model. There were significant differences in infectivity rates between the two strains (71 and 88% for DB versus 17 and 42% for mutant 11D2 at inocula of 10(3) and 10(4) CFU, respectively). In early adherence studies, parent DB adhered substantially better than the mutant to valvular vegetations at an inoculum of 10(6) CFU (P = 0.05). Southern blot analysis of colonies indicated that the location of the Tn917LTV1 insert in mutant 11D2 remained stable after animal passage. In vitro adherence assays revealed that mutant 11D2 was less adherent to cultured human endothelium than parent DB. These studies suggest that the sar locus is involved in the initial adherence of S. aureus to the fibrin-platelet-endothelium matrix on damaged valvular endothelium.

Full text

PDF
1724

Images in this article

1723Image
on p.1723

Selected References

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

  1. Bayer A. S. Staphylococcal bacteremia and endocarditis: state of the art. Arch Intern Med. 1982 Jun;142(6):1169–1177. [PubMed] [Google Scholar]
  2. Cheung A. L., Fischetti V. A. Role of surface proteins in staphylococcal adherence to fibers in vitro. J Clin Invest. 1989 Jun;83(6):2041–2049. doi: 10.1172/JCI114115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cheung A. L., Fischetti V. A. The role of fibrinogen in staphylococcal adherence to catheters in vitro. J Infect Dis. 1990 Jun;161(6):1177–1186. doi: 10.1093/infdis/161.6.1177. [DOI] [PubMed] [Google Scholar]
  4. Cheung A. L., Fischetti V. A. Variation in the expression of cell wall proteins of Staphylococcus aureus grown on solid and liquid media. Infect Immun. 1988 May;56(5):1061–1065. doi: 10.1128/iai.56.5.1061-1065.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. Cheung A. L., Koomey J. M., Lee S., Jaffe E. A., Fischetti V. A. Recombinant human tumor necrosis factor alpha promotes adherence of Staphylococcus aureus to cultured human endothelial cells. Infect Immun. 1991 Oct;59(10):3827–3831. doi: 10.1128/iai.59.10.3827-3831.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cheung A. L., Krishnan M., Jaffe E. A., Fischetti V. A. Fibrinogen acts as a bridging molecule in the adherence of Staphylococcus aureus to cultured human endothelial cells. J Clin Invest. 1991 Jun;87(6):2236–2245. doi: 10.1172/JCI115259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Clawson C. C., Rao G. H., White J. G. Platelet interaction with bacteria. IV. Stimulation of the release reaction. Am J Pathol. 1975 Nov;81(2):411–420. [PMC free article] [PubMed] [Google Scholar]
  9. Cohen M. L. Epidemiology of drug resistance: implications for a post-antimicrobial era. Science. 1992 Aug 21;257(5073):1050–1055. doi: 10.1126/science.257.5073.1050. [DOI] [PubMed] [Google Scholar]
  10. Donaldson D. M., Tew J. G. beta-Lysin of platelet origin. Bacteriol Rev. 1977 Jun;41(2):501–513. doi: 10.1128/br.41.2.501-513.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Drake T. A., Pang M. Effects of interleukin-1, lipopolysaccharide, and streptococci on procoagulant activity of cultured human cardiac valve endothelial and stromal cells. Infect Immun. 1989 Feb;57(2):507–512. doi: 10.1128/iai.57.2.507-512.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Drake T. A., Pang M. Staphylococcus aureus induces tissue factor expression in cultured human cardiac valve endothelium. J Infect Dis. 1988 Apr;157(4):749–756. doi: 10.1093/infdis/157.4.749. [DOI] [PubMed] [Google Scholar]
  13. Durack D. T., Beeson P. B. Experimental bacterial endocarditis. I. Colonization of a sterile vegetation. Br J Exp Pathol. 1972 Feb;53(1):44–49. [PMC free article] [PubMed] [Google Scholar]
  14. Espersen F., Frimodt-Møller N. Staphylococcus aureus endocarditis. A review of 119 cases. Arch Intern Med. 1986 Jun;146(6):1118–1121. [PubMed] [Google Scholar]
  15. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  16. Greenberg D. P., Bayer A. S., Cheung A. L., Ward J. I. Protective efficacy of protein A-specific antibody against bacteremic infection due to Staphylococcus aureus in an infant rat model. Infect Immun. 1989 Apr;57(4):1113–1118. doi: 10.1128/iai.57.4.1113-1118.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Hamill R. J., Vann J. M., Proctor R. A. Phagocytosis of Staphylococcus aureus by cultured bovine aortic endothelial cells: model for postadherence events in endovascular infections. Infect Immun. 1986 Dec;54(3):833–836. doi: 10.1128/iai.54.3.833-836.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Herzberg M. C., Gong K., MacFarlane G. D., Erickson P. R., Soberay A. H., Krebsbach P. H., Manjula G., Schilling K., Bowen W. H. Phenotypic characterization of Streptococcus sanguis virulence factors associated with bacterial endocarditis. Infect Immun. 1990 Feb;58(2):515–522. doi: 10.1128/iai.58.2.515-522.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. 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]
  21. Miller J. F., Mekalanos J. J., Falkow S. Coordinate regulation and sensory transduction in the control of bacterial virulence. Science. 1989 Feb 17;243(4893):916–922. doi: 10.1126/science.2537530. [DOI] [PubMed] [Google Scholar]
  22. Neu H. C. The crisis in antibiotic resistance. Science. 1992 Aug 21;257(5073):1064–1073. doi: 10.1126/science.257.5073.1064. [DOI] [PubMed] [Google Scholar]
  23. Ogawa S. K., Yurberg E. R., Hatcher V. B., Levitt M. A., Lowy F. D. Bacterial adherence to human endothelial cells in vitro. Infect Immun. 1985 Oct;50(1):218–224. doi: 10.1128/iai.50.1.218-224.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Peng H. L., Novick R. P., Kreiswirth B., Kornblum J., Schlievert P. Cloning, characterization, and sequencing of an accessory gene regulator (agr) in Staphylococcus aureus. J Bacteriol. 1988 Sep;170(9):4365–4372. doi: 10.1128/jb.170.9.4365-4372.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Perlman B. B., Freedman L. R. Experimental endocarditis. II. Staphylococcal infection of the aortic valve following placement of a polyethylene catheter in the left side of the heart. Yale J Biol Med. 1971 Oct;44(2):206–213. [PMC free article] [PubMed] [Google Scholar]
  26. Recsei P., Kreiswirth B., O'Reilly M., Schlievert P., Gruss A., Novick R. P. Regulation of exoprotein gene expression in Staphylococcus aureus by agar. Mol Gen Genet. 1986 Jan;202(1):58–61. doi: 10.1007/BF00330517. [DOI] [PubMed] [Google Scholar]
  27. Scheld W. M., Strunk R. W., Balian G., Calderone R. A. Microbial adhesion to fibronectin in vitro correlates with production of endocarditis in rabbits. Proc Soc Exp Biol Med. 1985 Dec;180(3):474–482. doi: 10.3181/00379727-180-42205. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. Smeltzer M. S., Hart M. E., Iandolo J. J. Phenotypic characterization of xpr, a global regulator of extracellular virulence factors in Staphylococcus aureus. Infect Immun. 1993 Mar;61(3):919–925. doi: 10.1128/iai.61.3.919-925.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Vann J. M., Proctor R. A. Ingestion of Staphylococcus aureus by bovine endothelial cells results in time- and inoculum-dependent damage to endothelial cell monolayers. Infect Immun. 1987 Sep;55(9):2155–2163. doi: 10.1128/iai.55.9.2155-2163.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Yeaman M. R., Norman D. C., Bayer A. S. Staphylococcus aureus susceptibility to thrombin-induced platelet microbicidal protein is independent of platelet adherence and aggregation in vitro. Infect Immun. 1992 Jun;60(6):2368–2374. doi: 10.1128/iai.60.6.2368-2374.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Yeaman M. R., Puentes S. M., Norman D. C., Bayer A. S. Partial characterization and staphylocidal activity of thrombin-induced platelet microbicidal protein. Infect Immun. 1992 Mar;60(3):1202–1209. doi: 10.1128/iai.60.3.1202-1209.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Yeaman M. R., Sullam P. M., Dazin P. F., Norman D. C., Bayer A. S. Characterization of Staphylococcus aureus-platelet binding by quantitative flow cytometric analysis. J Infect Dis. 1992 Jul;166(1):65–73. doi: 10.1093/infdis/166.1.65. [DOI] [PubMed] [Google Scholar]

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

RESOURCES