Staphylococcus aureus Exploits Cathelicidin Antimicrobial Peptides Produced during Early Pneumonia to Promote Staphylokinase‐Dependent Fibrinolysis
1Division of Infectious Disease, Children’s Hospital and Regional Medical Center, and Departments of 2Pediatrics and 3Medicine, University of Washington, Seattle
The increasing prevalence of Staphylococcus aureus strains isolated from hospital‐ and community‐acquired respiratory tract infections is an important public health concern worldwide. The majority of S. aureus strains produce staphylokinase, a plasminogen activator capable of inactivating neutrophil α‐defensins and of impairing phagocytosis via opsonin degradation. Cathelicidin antimicrobial peptides are present at sites of infection before the release of neutrophil α‐defensins. Therefore, we hypothesized that staphylokinase interacts with cathelicidin during the early pathogenesis of S. aureus airway infection. In a mouse intranasal infection model, cathelicidin was strongly up‐regulated in the airways during the development of staphylococcal pneumonia. In vitro, cathelicidin bound directly to staphylokinase and augmented staphylokinase‐dependent plasminogen activation and fibrinolysis at concentrations consistent with those detected in the airways during infection. These data suggest that staphylokinase production may be a novel virulence mechanism by which S. aureus exploits cathelicidin to promote fibrinolysis, leading to enhanced bacterial dissemination and invasive infection.
Received 6 September 2006; accepted 22 November 2006; electronically published 15 March 2007.
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Potential conflicts of interest: none reported.
Financial support: National Institutes of Health (grants AI007509 to M.H.B. and HL073996 to C.E.R.).