Fibronectin‐Binding Proteins and Fibrinogen‐Binding Clumping Factors Play Distinct Roles in Staphylococcal Arthritis and Systemic Inflammation

Abstract

Staphylococcus aureus is a commonly encountered pathogen in humans, and it has the potential to cause destructive and life-threatening conditions, including septic arthritis. The pathogenicity of staphylococci depends on the expression of virulence factors. Among these, staphylococcal cell-surface proteins with tissue-adhesive functions have been suggested to mediate the colonization of host tissues, a crucial step in the establishment of infection. We investigated the relative contribution of the fibronectin-binding proteins (FnBPs) and fibrinogen-binding clumping factors (Clfs) to staphylococcal virulence in an experimental model of septic arthritis. The results show that these 2 sets of proteins play distinctly different roles in the development and progression of septic arthritis. Although Clfs significantly contributed to the arthritogenicity of S. aureus, FnBPs had no effect on the development of arthritis. Conversely, FnBPs played an important role in the induction of systemic inflammation, characterized by interleukin-6 secretion, severe weight loss, and mortality.

Systemic Staphylococcus aureus infection mediated by Candida albicans hyphal invasion of mucosal tissue

“…In addition, five other adhesin mutants showed a similarly reduced ability (52-65 % attachment) to bind C. albicans, although these differences were not statistically significant due to larger SD. The creation of single, double, triple, or octuple mutants in these adhesins has been shown to eliminate the ability of S. aureus to both form biofilms and survive in vivo (Bose et al, 2012;Chen et al, 2013;Kenny et al, 2009;Mazmanian et al, 2000;Palmqvist et al, 2005). Therefore, these S. aureus mutants are no longer able to systemically spread in cases of co-infection with C. albicans regardless of the mechanism of deep tissue delivery.…”

Mouse model of hematogenous implant-related Staphylococcus aureus biofilm infection reveals therapeutic targets

“…AT is a secreted pore-forming toxin (34) found to promote biofilm formation in vitro (35,36) and to contribute to immune evasion in a murine model of orthopedic implant infection (37). ClfA is a surface-expressed fibrinogen-binding adhesin that has been shown to promote biofilm-like aggregations in synovial fluid (38) [providing a role for ClfA in septic arthritis (39,40)] and is highly expressed in human orthopedic implant infections (41). The anti-AT and anti-ClfA mAbs (0.5 μg/mL each) were first determined to have no effect, either alone or in combination, on the planktonic growth of NRS384 in broth culture (Fig.…”

Role of Fibronectin-Binding Proteins A and B inIn VitroCellular Infections andIn VivoSeptic Infections by Staphylococcus aureus

“…Therefore, high production of IL-6 in wild-type strain-or fnbB mutant-infected mice should be one of the major causes of significant alteration of body weight, unhealthy appearance, and drastic lethality. Palmqvist et al also demonstrated the contribution of FnBPs to systemic infection (40). They compared the pathogenicity of wild-type S. aureus strain LS-1 with its mutant lacking both fnbA and fnbB and demonstrated that the fnbA fnbB mutant caused no change in the body weights of mice and lower production of serum IL-6 than the wild-type strain.…”