Novel animal model for studying the molecular mechanisms of bacterial adhesion to bone‐implanted metallic devices: Role of fibronectin in Staphylococcus aureus adhesion

Abstract

Infection around metallic implants is a rare but severe complication of orthopaedic surgery. A novel animal model mimicking conditions of internal fixation devices was developed to evaluate the role of host proteins adsorbed on metallic devices in promoting adhesion and colonization of the material surfaces by Staphylococcus aureus. Small plates made of pure titanium were either fixed (three screws per plate) onto the iliac bones of guinea pigs or implanted into their subcutaneous space as controls. Five to 6 weeks after surgery, the plates and screws were removed from the previously killed animals, carefully rinsed in buffer, and tested in an in vitro assay of S. aureus adhesion to metallic surfaces. To evaluate the role of fibronectin in staphylococcal adhesion to explanted plates and screws, a mutant of S. aureus that is specifically defictive in fibronectin adhesion due to decreased expression of the fibronectin adhesin was compared with its isogenic parental strain. A significant reduction in adhesion of the fibronectin adhesin-defective mutant compared with the parental strain occurred on both the subcutaneously implanted and bone-implanted metallic plates. The results of this specific biological assay suggest that fibronectin is present on bone-implanted metallic devices and promotes attachment of S. aureus to their surfaces. This novel experimental model should help, to characterize several parameters of bacterial adhesion to metallic orthopaedic devices and to develop novel anti-adhesive strategies for preventing such infections.

Relevant Role of Fibronectin-Binding Proteins in Staphylococcus aureus Biofilm-Associated Foreign-Body Infections

“…In their study, Bisognano et al showed that LexA is a repressor of fnbB expression, and consequently, SOS response induction by commonly used fluoroquinolones resulted in the increased expression of the FnBPB protein on the bacterial surface (7). As FnBPs have been shown to play an important role during invasion of mammalian cells (47,48) and in mediating adherence to different host extracellular matrix components, such as fibronectin, fibrinogen, elastin, or tropoelastin (23,43,55), an adverse consequence of SOS induction by antibiotics would be that it might facilitate colonization of host cells and medical implants (13,17). Accordingly, our results suggest that an increase in FnBPB expression through activation of the SOS response is sufficient to induce a noticeable increase in the capacity of the strain to produce multicellular communities on abiotic surfaces in vitro.…”

Reassessing the Role of Staphylococcus aureus Clumping Factor and Fibronectin-Binding Protein by Expression in Lactococcus lactis

“…The implication of the S. aureus fibronectin-binding proteins was established in a few models of foreign-body infection, including colonization of titanium plates removed from the iliac bones of guinea pigs (8) and colonization of PMMA slides explanted from tissue cages in the same animal (14). On the other hand, two studies performed on rats with experimental endocarditis produced conflicting results.…”

Staphylococcus aureus Infections: Epidemiology, Pathophysiology, Clinical Manifestations, and Management

“…These bacterial cell surface receptors are known as adhesins or MSCRAMMs (microbial surface components recognizing adhesive matrix molecules) (417,418). Strains of S. aureus lacking genes that encode certain MSCRAMMs are less likely to cause osteoarticular infections in animal models (417,419,420). S. aureus is also able to form biofilms on foreign materials that act as sanctuary sites, where it is relatively protected from antimicrobial agents and the host immune response (421).…”