Surface-associated proteins from Staphylococcus aureus demonstrate potent bone resorbing activity

Abstract

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.

The bacterial gene lfpA influences the potent induction of calcitonin receptor and osteoclast-related genes in Burkholderia pseudomallei-induced TRAP-positive multinucleated giant cells

“…Bacterially induced osteoclastogenesis is not without precedent (see review by Nair et al, 1996). Multinucleation and TRAP production by spleen cells has been reported following treatment with Porphyromonas gingivalis, a periodontal pathogen, or lipopolysaccharide from E. coli (Abu-Amer et al, 1997;Jiang et al, 2002), and the addition of surface-associated material from P. gingivalis, Actinobacillus actinomycetemcomitans, or Staphylococcus aureus to bone marrow cultures reportedly causes multinucleation and bone resorption in vitro (Wilson et al, 1986;Wilson et al, 1993;Nair et al, 1995), although this effect may be due to an increase in RANKL by associated osteoblasts, rather than a direct effect on osteoclast precursors. However, incubation periods of 10 days or more were routine in these studies.…”

Interaction of staphylococci with bone

“…Neutralisation of TNFα and IL-6 fully abolishes SAM-stimulated osteoclastogenesis, with antagonism of IL-1 having only a partial effect (Meghji et al, 1998; Nair et al, 1995). The effect of this SAM on osteoclast formation and stimulation of resorption does not require co-culture with osteoblasts, and does not require RANKL signalling (Lau et al, 2006).…”

“…Work in our own laboratory has shown that S. aureus and S. epidermidis produce surface-associated proteins that can stimulate bone breakdown in an in vitro assay (Meghji et al, 1997; Nair et al, 1995). These surface-associated proteins and capsular material appear to promote the formation and activation of the bone-resorbing osteoclast (Lau et al, 2006; Meghji et al, 1998).…”

Apoptosis-associated uncoupling of bone formation and resorption in osteomyelitis

“…As such, any interference with these integrated cell types can result in abnormal bone remodeling. Bacteria such as S. aureus and their products can be potent stimulators of resorptive bone loss (Nair et al, 1995, 1996). While bacteria can directly damage bone by producing acids and proteases, they can also stimulate osteoclastogenesis.…”