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, Δcoa, Δvwb, and Δcoa Δvwb) 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 Δcoa Δvwb and Δvwb variants compared to WT or Δcoa 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 Δvwb strain was used. Importantly, no difference in
arthritis severity between the Δvwb 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.