Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1997 Oct;65(10):4216–4221. doi: 10.1128/iai.65.10.4216-4221.1997

The role of staphylococcal polysaccharide microcapsule expression in septicemia and septic arthritis.

I M Nilsson 1, J C Lee 1, T Bremell 1, C Rydén 1, A Tarkowski 1
PMCID: PMC175605  PMID: 9317029

Abstract

Staphylococcus aureus arthritis is a rapidly progressive and highly erosive disease of the joints in which both host and bacterial factors are of pathogenic importance. One potential bacterial virulence factor is the ability to express a polysaccharide capsule (CP). Among 11 reported capsular serotypes, CP type 5 (CP5) and CP8 comprise 80 to 85% of all clinical blood isolates. The aim of this study was to assess the role of CP5 as a virulence factor in staphylococcal septicemia and septic arthritis with a recently established murine model of hematogenously spread S. aureus arthritis. NMRI mice were inoculated intravenously with S. aureus strains isogenic for expression of CP5, and clinical, bacteriological, serological, and histopathological progression of disease was studied. Inoculation of 7 x 10(6) CFU of S. aureus per mouse induced 55% mortality in the group inoculated with the CP-expressing bacteria, compared to 18% in the group inoculated with CP- mutants. A lower dose of inoculum (3 x 10[6] per mouse) did not give rise to mortality in mice inoculated with CP mutant strains, whereas 18% of the mice inoculated with the CP5-expressing S. aureus died. Importantly, mice inoculated with S. aureus expressing CP5 had a significantly higher frequency of arthritis and a more severe form of the disease. In vitro assays suggested that macrophages were not able to phagocytize CP5+ staphylococci as efficiently as they were CP5- strains. In addition, once phagocytized, CP5+ bacteria were less efficiently killed than CP- mutants. In summary, CP5 leads to a higher frequency of arthritis and a more severe course of the disease. This seems to be related to the effects of the downregulatory properties of CP on the ingestion and intracellular killing capacity of phagocytes. Our results clearly indicate that the expression of CP5 is a determinant of the virulence of S. aureus in arthritis and septicemia.

Full Text

The Full Text of this article is available as a PDF (1.0 MB).

Selected References

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

  1. Abdelnour A., Arvidson S., Bremell T., Rydén C., Tarkowski A. The accessory gene regulator (agr) controls Staphylococcus aureus virulence in a murine arthritis model. Infect Immun. 1993 Sep;61(9):3879–3885. doi: 10.1128/iai.61.9.3879-3885.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Abdelnour A., Bremell T., Holmdahl R., Tarkowski A. Clonal expansion of T lymphocytes causes arthritis and mortality in mice infected with toxic shock syndrome toxin-1-producing staphylococci. Eur J Immunol. 1994 May;24(5):1161–1166. doi: 10.1002/eji.1830240523. [DOI] [PubMed] [Google Scholar]
  3. Albus A., Arbeit R. D., Lee J. C. Virulence of Staphylococcus aureus mutants altered in type 5 capsule production. Infect Immun. 1991 Mar;59(3):1008–1014. doi: 10.1128/iai.59.3.1008-1014.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Baddour L. M., Lowrance C., Albus A., Lowrance J. H., Anderson S. K., Lee J. C. Staphylococcus aureus microcapsule expression attenuates bacterial virulence in a rat model of experimental endocarditis. J Infect Dis. 1992 Apr;165(4):749–753. doi: 10.1093/infdis/165.4.749. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. 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]
  7. Fattom A., Schneerson R., Szu S. C., Vann W. F., Shiloach J., Karakawa W. W., Robbins J. B. Synthesis and immunologic properties in mice of vaccines composed of Staphylococcus aureus type 5 and type 8 capsular polysaccharides conjugated to Pseudomonas aeruginosa exotoxin A. Infect Immun. 1990 Jul;58(7):2367–2374. doi: 10.1128/iai.58.7.2367-2374.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Goldenberg D. L., Reed J. I. Bacterial arthritis. N Engl J Med. 1985 Mar 21;312(12):764–771. doi: 10.1056/NEJM198503213121206. [DOI] [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. Karakawa W. W., Fournier J. M., Vann W. F., Arbeit R., Schneerson R. S., Robbins J. B. Method for the serological typing of the capsular polysaccharides of Staphylococcus aureus. J Clin Microbiol. 1985 Sep;22(3):445–447. doi: 10.1128/jcm.22.3.445-447.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lee J. C., Betley M. J., Hopkins C. A., Perez N. E., Pier G. B. Virulence studies, in mice, of transposon-induced mutants of Staphylococcus aureus differing in capsule size. J Infect Dis. 1987 Nov;156(5):741–750. doi: 10.1093/infdis/156.5.741. [DOI] [PubMed] [Google Scholar]
  12. Lee J. C., Perez N. E., Hopkins C. A., Pier G. B. Purified capsular polysaccharide-induced immunity to Staphylococcus aureus infection. J Infect Dis. 1988 Apr;157(4):723–730. doi: 10.1093/infdis/157.4.723. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Markwell M. A. A new solid-state reagent to iodinate proteins. I. Conditions for the efficient labeling of antiserum. Anal Biochem. 1982 Sep 15;125(2):427–432. doi: 10.1016/0003-2697(82)90025-2. [DOI] [PubMed] [Google Scholar]
  15. Marrack P., Blackman M., Kushnir E., Kappler J. The toxicity of staphylococcal enterotoxin B in mice is mediated by T cells. J Exp Med. 1990 Feb 1;171(2):455–464. doi: 10.1084/jem.171.2.455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Miethke T., Wahl C., Heeg K., Echtenacher B., Krammer P. H., Wagner H. T cell-mediated lethal shock triggered in mice by the superantigen staphylococcal enterotoxin B: critical role of tumor necrosis factor. J Exp Med. 1992 Jan 1;175(1):91–98. doi: 10.1084/jem.175.1.91. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Nemeth J., Lee J. C. Antibodies to capsular polysaccharides are not protective against experimental Staphylococcus aureus endocarditis. Infect Immun. 1995 Feb;63(2):375–380. doi: 10.1128/iai.63.2.375-380.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Paliard X., West S. G., Lafferty J. A., Clements J. R., Kappler J. W., Marrack P., Kotzin B. L. Evidence for the effects of a superantigen in rheumatoid arthritis. Science. 1991 Jul 19;253(5017):325–329. doi: 10.1126/science.1857971. [DOI] [PubMed] [Google Scholar]
  19. Peterson P. K., Wilkinson B. J., Kim Y., Schmeling D., Quie P. G. Influence of encapsulation on staphylococcal opsonization and phagocytosis by human polymorphonuclear leukocytes. Infect Immun. 1978 Mar;19(3):943–949. doi: 10.1128/iai.19.3.943-949.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Rydén C., Yacoub A. I., Maxe I., Heinegård D., Oldberg A., Franzén A., Ljungh A., Rubin K. Specific binding of bone sialoprotein to Staphylococcus aureus isolated from patients with osteomyelitis. Eur J Biochem. 1989 Sep 15;184(2):331–336. doi: 10.1111/j.1432-1033.1989.tb15023.x. [DOI] [PubMed] [Google Scholar]
  21. Soell M., Diab M., Haan-Archipoff G., Beretz A., Herbelin C., Poutrel B., Klein J. P. Capsular polysaccharide types 5 and 8 of Staphylococcus aureus bind specifically to human epithelial (KB) cells, endothelial cells, and monocytes and induce release of cytokines. Infect Immun. 1995 Apr;63(4):1380–1386. doi: 10.1128/iai.63.4.1380-1386.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Verbrugh H. A., Peterson P. K., Nguyen B. Y., Sisson S. P., Kim Y. Opsonization of encapsulated Staphylococcus aureus: the role of specific antibody and complement. J Immunol. 1982 Oct;129(4):1681–1687. [PubMed] [Google Scholar]
  23. Wiley B. B., Maverakis N. H. Capsule production and virulence among strains of Staphylococcus aureus. Ann N Y Acad Sci. 1974 Jul 31;236(0):221–232. doi: 10.1111/j.1749-6632.1974.tb41493.x. [DOI] [PubMed] [Google Scholar]
  24. Wilkinson B. J., Peterson P. K., Quie P. G. Cryptic peptidoglycan and the antiphagocytic effect of the Staphylococcus aureus capsule: model for the antiphagocytic effect of bacterial cell surface polymers. Infect Immun. 1979 Feb;23(2):502–508. doi: 10.1128/iai.23.2.502-508.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Xu S., Arbeit R. D., Lee J. C. Phagocytic killing of encapsulated and microencapsulated Staphylococcus aureus by human polymorphonuclear leukocytes. Infect Immun. 1992 Apr;60(4):1358–1362. doi: 10.1128/iai.60.4.1358-1362.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Zhao Y. X., Abdelnour A., Holmdahl R., Tarkowski A. Mice with the xid B cell defect are less susceptible to developing Staphylococcus aureus-induced arthritis. J Immunol. 1995 Aug 15;155(4):2067–2076. [PubMed] [Google Scholar]

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

RESOURCES