The Expression of von Willebrand Factor-Binding Protein Determines Joint-Invading Capacity of Staphylococcus aureus, a Core Mechanism of Septic Arthritis

Septic arthritis, one of the most dangerous joint diseases, is predominantly caused by Staphylococcus aureus In contrast, coagulase-negative staphylococci are rarely found in septic arthritis. We hypothesize that coagulases released by S. aureus , including coagulase (Coa) and von Willebrand factor-binding protein (vWbp), play potent roles in the induction of septic arthritis. Four isogenic S. aureus strains differing in expression of coagulases (wild-type [WT] Newman, Δ coa , Δ vwb , and Δ coa Δ vwb ) were used to induce septic arthritis in both wild-type and von Willebrand factor (vWF)-deficient mice. Septic arthritis severity was greatly reduced when wild-type mice were infected with the Δ coa Δ vwb and Δ vwb variants compared to WT or Δ coa strains, suggesting that vWbp rather than Coa is a major virulence factor in S. aureus septic arthritis. vWF-deficient mice were more susceptible to bone damage in septic arthritis, especially when the Δ vwb strain was used. Importantly, no difference in arthritis severity between the Δ vwb and WT strains was observed in vWF-deficient mice. Collectively, we conclude that vWbp production by S. aureus enhances staphylococcal septic arthritis. IMPORTANCE Septic arthritis remains one of the most dangerous joint diseases with a rapidly progressive disease character. Despite advances in the use of antibiotics, permanent reductions in joint function due to joint deformation and deleterious contractures occur in up to 50% of patients with septic arthritis. So far, it is still largely unknown how S. aureus initiates and establishes joint infection. Here, we demonstrate that von Willebrand factor-binding protein expressed by S. aureus facilitates the initiation of septic arthritis. Such effect might be mediated through its interaction with a host factor (von Willebrand factor). Our finding contributes significantly to the full understanding of septic arthritis etiology and will pave the way for new therapeutic modalities for this devastating disease.