Fibronectin, a large and essential multidomain glycoprotein, with multiple adhesive properties, functioning as a key link between cells and their extracellular matrices, is now recognized to be the target for a large number of bacterial proteins, which are generally considered to function as bacterial adhesins. In the last decade, an avalanche of bacterial fibronectin-binding proteins (FnBPs) has been identified, and the bioinformatics, structural biology, biological function and role in the virulence of a growing number of both Gram-positive and Gram-negative proteins have begun to emerge. The evidence suggests that fibronectin has a wider biological remit than was previously thought and that bacterial FnBPs have actions over and above that of simple adhesion. This article provides an update on our current understanding of FnBPs from both Gram-negative and Gram-positive bacteria and their proposed roles in bacterial colonization, bacterial virulence and bacteria-host interactions.

Normal bone remodelling requires the coordinated regulation of the genesis and activity of osteoblast and osteoclast lineages. Any interference with these integrated cellular systems can result in dysregulation of remodelling with the consequent loss of bone matrix. Bacteria are important causes of bone pathology in common conditions such as periodontitis, dental cysts, bacterial arthritis, and osteomyelitis. It is now established that many of the bacteria implicated in bone diseases contain or produce molecules with potent effects on bone cells. Some of these molecules, such as components of the gram-positive cell walls (lipoteichoic acids), are weak stimulators of bone resorption in vitro, while others (PMT, cpn60) are as active as the most active mammalian osteolytic factors such as cytokines like IL-1 and TNF. The complexity of the integration of bone cell lineage development means that there are still question marks over the mechanism of action of many well-known bone-modulatory molecules such as parathyroid hormone. The key questions which must be asked of the now-recognized bacterial bone-modulatory molecules are as follows: (i) what cell population do they bind to, (ii) what is the nature of the receptor and postreceptor events, and (iii) is their action direct or dependent on the induction of secondary extracellular bone-modulating factors such as cytokines, eicosanoids, etc. In the case of LPS, this ubiquitous gram-negative polymer probably binds to osteoblasts or other cells in bone through the CD14 receptor and stimulates them to release cytokines and eicosanoids which then induce the recruitment and activation of osteoclasts. This explains the inhibitor effects of nonsteroidal and anticytokine agents on LPS-induced bone resorption. However, other bacterial factors such as the potent toxin PMT may act by blocking the normal maturation pathway of the osteoblast lineage, thus inducing dysregulation in the tightly regulated process of resorption and replacement of bone matrix. At the present time, it is not possible to define a general mechanism by which bacteria promote loss of bone matrix. Many bacteria are capable of stimulating bone matrix loss, and the information available would suggest that each organism possesses different factors which interact with bone in different ways. With the rapid increase in antibiotic resistance, particularly with Staphylococcus aureus and M. tuberculosis, organisms responsible for much bone pathology in developed countries only two generations ago, we would urge that much greater attention should be focused on the problem of bacterially induced bone remodelling in order to define pathogenetic mechanisms which could be therapeutic targets for the development of new treatment modalities.

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.