ROLE OF THE STAPHYLOCOCCAL ACCESSORY GENE REGULATOR (SAR) IN SEPTIC ARTHRITIS

Staphylococcus aureus arthritis is a highly erosive disease in which b oth host and bacterial factors are of importance for its induction and progression. At the transcriptional level, three known loci act in re gulating production of exoproteins and expression of cell wall structu res. 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 rece ntly established murine model of hematogenously spread S. aureus arthr itis was employed. S. aureus strains, isogenic for the sar locus, were inoculated intravenously into NMRI mice, and the clinical, bacteriolo gical, serological, and histopathological progression of the disease w as 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 exhibit ed a more pronounced T- and B-lymphocyte activation than those inocula ted with the sar mutant, evidenced by splenomegaly, polyclonal B-cell activation, and high serum levels of interleukin 6 and gamma interfero n. Also, infection with sar(+) staphylococci induced a pronounced weig ht loss. To assess the relationship between clinical signs and spread of bacteria, we analyzed the homing pattern and persistence of S. aure us in host tissues. Kidneys and joints form sar(+)-inoculated subjects displayed a higher degree of bacterial persistence than other organs. Our results suggests that molecules controlled by the sar locus are i mportant virulence determinants in the induction and progression of se ptic arthritis.