Interaction of staphylococci with bone

Abstract

Staphylococci, in particular Staphylococcus aureus, are the predominant cause of bone infections worldwide. These infections are painful, debilitating and with the rise in antibiotic-resistant forms, increasingly difficult to treat. The growth in the number of prosthetic joint replacement procedures also provides new opportunities for these infections to take hold. Comprehending the mechanisms by which staphylococci interact with and damage bone is critical to the development of new approaches to meet this challenge. This review summarises current understanding of the mechanisms by which staphylococci infect and damage bone. We address the role of the inflammatory response to staphylococcal infection in disrupting the homeostatic balance of bone matrix deposition and resorption and thereby mediating bone destruction. A number of virulence factors that have been shown to contribute to bone infection and pathology are discussed, however no single factor has been defined as being specific to bone infections. Although traditionally considered an extracellular pathogen, there is increasing evidence that staphylococci are able to invade host cells, and that an intracellular lifestyle may facilitate long-term persistence in bone tissue, enabling evasion of antimicrobials and host immune responses. ‘Small colony variant’ strains, with mutations disabling the electron transport pathway appear particularly adept at invading and persisting within host cells, and exhibit enhanced antimicrobial resistance, and may represent a further complication in the treatment and management of staphylococcal bone disease.

Osteoprotegerin gene polymorphism is not associated with prosthetic joint infection after total joint arthroplasty in the Czech population

“…This was effectively prevented by inhibition of RANKL (receptor activator of nuclear factor -kappa B ligand) signalling. This and other experiments support the clinical observation of a tight association between the development of infection and increased resorption of periprosthetic bone 5 . For this reason, cytokine ligands and the corresponding receptors that regulate osteoclast accumulation, maturation and viability, are probably involved in the complex pathogenesis of PJI.…”

Clinical Significance and Pathogenesis of Staphylococcal Small Colony Variants in Persistent Infections

“…Staphylococci, including S. aureus and coagulase-negative staphylococci, are by far the most frequent pathogens involved in bone and joint infections (40,45). In general, osteoarticular infections are difficult to treat and in most cases require a combined treatment of surgical interventions and long-term antibiotic regimens (45,46). Nevertheless, infections that have apparently been treated successfully have a high recurrence rate and can relapse even after several years (8,44).…”

“…In most cases, a high phenotypic diversity of infecting pathogens, including normal, small, and SCV-like phenotypes, is found on agar plates when tissue samples of chronic bone infections are plated. The tendency of staphylococci to cause chronic bone and joint infections is only marginally understood but might originate in the complex bacterial interaction with bone tissue (46).…”

Potential Role of Fibroblast-Like Synoviocytes in Joint Damage Induced by Brucella abortus Infection through Production and Induction of Matrix Metalloproteinases

“…However, when the infection is not quickly cleared by the host, the potent activation of the immune response with the associated high levels of cytokines leads to joint destruction. High cytokine concentrations increase the release of host matrix metalloproteinases (MMPs) that degrade collagen and thus lead to cartilage loss (15,44,54).…”