Formylated peptides are important virulence factors in Staphylococcus aureus arthritis in mice

Abstract

Background: Staphylococcus aureus is the most common pathogen causing septic arthritis in humans. The affected joints are often rapidly and permanently damaged despite antibiotic treatment, indicating that the elicited host immune response contributes substantially to joint destruction. Bacterial formylated peptides are important chemotactic molecules mediating neutrophil recruitment into infected tissues as an important first step of host defense against invading bacteria. The role of formylated peptides in S. aureus infections has been unknown.

Methods: Mice were intravenously inoculated with wild-type S. aureus strain RN4220 or its isogenic mutant strain (Δfmt) lacking the ability to produce formylated peptides. The development of arthritis was followed clinically and histopathologically.

Results: Mice inoculated with the formyl peptide-producing wild-type strain showed a significantly increased frequency and severity of arthritis and subsequent joint destruction as compared with Δfmt mutant strain-inoculated mice. The wild-type S. aureus strain also induced significantly more weight loss than the Δfmt mutant strain. The recruitment of neutrophils into infected kidneys and synovial tissue was significantly higher in mice inoculated with the wild-type strain.

Conclusions: Our data show that formylated peptides function as important virulence factors in S. aureus arthritis, partly by mediating neutrophil recruitment, which contributes substantially to the joint damage.