Surface-associated proteins from Staphylococcus aureus demonstrate potent bone resorbing activity.
Staphylococcus aureus infections are associated with rapid bone destruction in conditions such as osteomyelitis, bacterial arthritis, and infected orthopedic implant failure. How this bacterium induces bone destruction has not been defined. In studies of the role of oral Gram-negative bacteria in periodontal pathology, we have established that cell surface-associated proteins (SAPs) are potent stimulators of bone resorption. The surface-associated components from S. aureus have now been isolated and demonstrated to be extremely potent stimulators of bone resorption in the murine calvarial bone resorption assay. Bone resorption appears to be due to proteins, is not the result of contamination with lipoteichoic acid or muramyl dipeptide, and is potently inhibited by indomethacin and can be completely blocked by high concentrations of interleukin-1 receptor antagonist or TN3-19.12, a neutralizing monoclonal antibody to murine TNF. The SAP fraction can stimulate fibroblasts or monocytes to release osteolytic cytokines, but only at high concentrations. Fractionation of the SAPs by high performance liquid chromatography demonstrated that a number of fractions were osteolytically active. The most active contained a heterodimeric protein of molecular weight 32-36 kD. The presence of this osteolytically active surface-associated fraction may account for the bone resorption associated with local infection with S. aureus.
Nair
S
S
Maxillofacial Surgery Research Unit, Eastman Dental Institute for Oral Health Care Sciences, London, United Kingdom.
Song
Y
Y
Meghji
S
S
Reddi
K
K
Harris
M
M
Ross
A
A
Poole
S
S
Wilson
M
M
Henderson
B
B
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity*; D001862:Bone Resorption / Q000139:chemically induced* / Q000188:drug therapy; D005591:Chemical Fractionation; D002851:Chromatography, High Pressure Liquid; D016207:Cytokines / Q000096:biosynthesis; D015232:Dinoprostone / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology / Q000627:therapeutic use; D008070:Lipopolysaccharides / Q000633:toxicity; D008565:Membrane Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity*; D051379:Mice; D008854:Microscopy, Electron; D008970:Molecular Weight; D011863:Radioimmunoassay; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D013203:Staphylococcal Infections / Q000503:physiopathology; D013211:Staphylococcus aureus / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D013302:Streptomyces / Q000378:metabolism; D013682:Teichoic Acids / Q000633:toxicity; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000911:Antibodies, Monoclonal; D001426:Bacterial Proteins; D016207:Cytokines; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D017472:Receptors, Interleukin-1; D013682:Teichoic Acids; D014409:Tumor Necrosis Factor-alpha; C009900:lipoteichoic acid; D015232:Dinoprostone; D007213:Indomethacin