title: Staphylococcus aureus protein A binds to osteoblasts and triggers signals that weaken bone in osteomyelitis.
abstract: Osteomyelitis is a debilitating infectious disease of the bone. It is predominantly caused by S. aureus and is associated with significant morbidity and mortality. It is characterised by weakened bones associated with progressive bone loss. Currently the mechanism through which either bone loss or bone destruction occurs in osteomyelitis patients is poorly understood. We describe here for the first time that the major virulence factor of S. aureus, protein A (SpA) binds directly to osteoblasts. This interaction prevents proliferation, induces apoptosis and inhibits mineralisation of cultured osteoblasts. Infected osteoblasts also increase the expression of RANKL, a key protein involved in initiating bone resorption. None of these effects was seen in a mutant of S. aureus lacking SpA. Complementing the SpA-defective mutant with a plasmid expressing spa or using purified protein A resulted in attachment to osteoblasts, inhibited proliferation and induced apoptosis to a similar extent as wildtype S. aureus. These events demonstrate mechanisms through which loss of bone formation and bone weakening may occur in osteomyelitis patients. This new information may pave the way for the development of new and improved therapeutic agents to treat this disease.
authors.affiliation: Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: Tania
authors.initials: T
authors.lastname: Claro
authors.forename: Amro
authors.initials: A
authors.lastname: Widaa
authors.forename: Maghnus
authors.initials: M
authors.lastname: O'Seaghdha
authors.forename: Helen
authors.initials: H
authors.lastname: Miajlovic
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Foster
authors.forename: Fergal J
authors.initials: FJ
authors.lastname: O'Brien
authors.forename: Steven W
authors.initials: SW
authors.lastname: Kerrigan
mesh_terms: D000818:Animals; D017209:Apoptosis; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology*; D002113:Calcification, Physiologic; D002460:Cell Line; D049109:Cell Proliferation; D051379:Mice; D008954:Models, Biological; D010006:Osteoblasts / Q000378:metabolism* / Q000382:microbiology; D010019:Osteomyelitis / Q000382:microbiology* / Q000473:pathology; D053244:Osteoprotegerin / Q000378:metabolism; D011485:Protein Binding; D053245:RANK Ligand / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D015398:Signal Transduction; D013205:Staphylococcal Protein A / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000378:metabolism*
chemical_list: D053244:Osteoprotegerin; D053245:RANK Ligand; D047888:Receptors, Tumor Necrosis Factor, Type I; D013205:Staphylococcal Protein A