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. 1996 Nov;64(11):4438–4443. doi: 10.1128/iai.64.11.4438-4443.1996

Role of the staphylococcal accessory gene regulator (sar) in septic arthritis.

I M Nilsson 1, T Bremell 1, C Rydén 1, A L Cheung 1, A Tarkowski 1
PMCID: PMC174395  PMID: 8890189

Abstract

Staphylococcus aureus arthritis is a highly erosive disease in which both host and bacterial factors are of importance for its induction and progression. At the transcriptional level, three known loci act in regulating production of exoproteins and expression of cell wall structures. The aim of our study was to assess the role of the sar locus as a virulence determinant in the pathogenesis of septic arthritis. A recently established murine model of hematogenously spread S. aureus arthritis was employed. S. aureus strains, isogenic for the sar locus, were inoculated intravenously into NMRI mice, and the clinical, bacteriological, serological, and histopathological progression of the disease was studied. Within 1 week after inoculation of bacteria, the frequency of arthritis was 79% in the group of mice inoculated with the sar+ strain, whereas the corresponding frequency in sar mutants was 21% (P < 0.01). Mice inoculated with the sar+ staphylococcal strain exhibited a more pronounced T- and B-lymphocyte activation than those inoculated with the sar mutant, evidenced by splenomegaly, polyclonal B-cell activation, and high serum levels of interleukin 6 and gamma interferon. Also, infection with sar+ staphylococci induced a pronounced weight loss. To assess the relationship between clinical signs and spread of bacteria, we analyzed the homing pattern and persistence of S. aureus in host tissues. Kidneys and joints from sar+-inoculated subjects displayed a higher degree of bacterial persistence than other organs. Our results suggest that molecules controlled by the sar locus are important virulence determinants in the induction and progression of septic arthritis.

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Selected References

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  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., Tarkowski A. Toxic shock syndrome toxin 1 contributes to the arthritogenicity of Staphylococcus aureus. J Infect Dis. 1994 Jul;170(1):94–99. doi: 10.1093/infdis/170.1.94. [DOI] [PubMed] [Google Scholar]
  3. Abdelnour A., Tarkowski A. Polyclonal B-cell activation by an arthritogenic Staphylococcus aureus strain: contribution of T-cells and monokines. Cell Immunol. 1993 Apr 1;147(2):279–293. doi: 10.1006/cimm.1993.1069. [DOI] [PubMed] [Google Scholar]
  4. Bomalaski J. S., Ford T., Hudson A. P., Clark M. A. Phospholipase A2-activating protein induces the synthesis of IL-1 and TNF in human monocytes. J Immunol. 1995 Apr 15;154(8):4027–4031. [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. Bremell T., Tarkowski A. Preferential induction of septic arthritis and mortality by superantigen-producing staphylococci. Infect Immun. 1995 Oct;63(10):4185–4187. doi: 10.1128/iai.63.10.4185-4187.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. 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]
  10. Cheung A. L., Ying P. Regulation of alpha- and beta-hemolysins by the sar locus of Staphylococcus aureus. J Bacteriol. 1994 Feb;176(3):580–585. doi: 10.1128/jb.176.3.580-585.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Durkin J. P., Shier W. T. Staphylococcal delta toxin stimulates endogenous phospholipase A2 activity and prostaglandin synthesis in fibroblasts. Biochim Biophys Acta. 1981 Feb 23;663(2):467–479. doi: 10.1016/0005-2760(81)90175-2. [DOI] [PubMed] [Google Scholar]
  12. Farrar M. A., Schreiber R. D. The molecular cell biology of interferon-gamma and its receptor. Annu Rev Immunol. 1993;11:571–611. doi: 10.1146/annurev.iy.11.040193.003035. [DOI] [PubMed] [Google Scholar]
  13. Franzén A., Heinegård D. Isolation and characterization of two sialoproteins present only in bone calcified matrix. Biochem J. 1985 Dec 15;232(3):715–724. doi: 10.1042/bj2320715. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. Green J., Schotland S., Sella Z., Kleeman C. R. Interleukin-6 attenuates agonist-mediated calcium mobilization in murine osteoblastic cells. J Clin Invest. 1994 Jun;93(6):2340–2350. doi: 10.1172/JCI117239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. Mahowald M. L. Animal models of infectious arthritis. Clin Rheum Dis. 1986 Aug;12(2):403–421. [PubMed] [Google Scholar]
  18. 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]
  19. 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]
  20. 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]
  21. Rogolsky M. Nonenteric toxins of Staphylococcus aureus. Microbiol Rev. 1979 Sep;43(3):320–360. doi: 10.1128/mr.43.3.320-360.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. Smith B. D., Martin G. R., Miller E. J., Dorfman A., Swarm R. Nature of the collagen synthesized by a transplanted chondrosarcoma. Arch Biochem Biophys. 1975 Jan;166(1):181–186. doi: 10.1016/0003-9861(75)90378-1. [DOI] [PubMed] [Google Scholar]
  24. Umezawa K., Weinstein I. B., Shaw W. V. Staphylococcal delta-hemolysin inhibits cellular binding of epidermal growth factor and induces arachidonic acid release. Biochem Biophys Res Commun. 1980 May 30;94(2):625–629. doi: 10.1016/0006-291x(80)91278-4. [DOI] [PubMed] [Google Scholar]
  25. Vadas P., Pruzanski W., Kim J., Fornasier V. The proinflammatory effect of intra-articular injection of soluble human and venom phospholipase A2. Am J Pathol. 1989 Apr;134(4):807–811. [PMC free article] [PubMed] [Google Scholar]
  26. Yatohgo T., Izumi M., Kashiwagi H., Hayashi M. Novel purification of vitronectin from human plasma by heparin affinity chromatography. Cell Struct Funct. 1988 Aug;13(4):281–292. doi: 10.1247/csf.13.281. [DOI] [PubMed] [Google Scholar]
  27. 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]

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