Role of the staphylococcal accessory gene regulator (sar) in septic arthritis.
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.
Department of Clinical Immunology, University of Göteborg, Sweden.
I M
IM
Nilsson
T
T
Bremell
C
C
Rydén
A L
AL
Cheung
A
A
Tarkowski
D000818:Animals; D001170:Arthritis, Infectious / Q000382:microbiology*; D003094:Collagen / Q000378:metabolism; D005260:Female; D005798:Genes, Bacterial; D005809:Genes, Regulator; D058574:Integrin-Binding Sialoprotein; D007371:Interferon-gamma / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007596:Joints / Q000382:microbiology; D007668:Kidney / Q000382:microbiology; D007958:Leukocyte Count; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D009504:Neutrophils; D012795:Sialoglycoproteins / Q000378:metabolism; D013203:Staphylococcal Infections / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity*; D014774:Virulence; D019096:Vitronectin / Q000378:metabolism
C546872:Ibsp protein, mouse; D058574:Integrin-Binding Sialoprotein; D015850:Interleukin-6; D012795:Sialoglycoproteins; D019096:Vitronectin; D007371:Interferon-gamma; D003094:Collagen