Role of Staphylococcus aureus capsular polysaccharide in osteoclastogenesis

Abstract

Staphylococcus aureus isolates lacking capsular polysaccharide (CP) expression (NT) are frequently recovered from patients with chronic osteomyelitis. It has been proposed that the loss of CP expression during long term bone infection is the consequence of bacterial microevolution in the bone and it could represent an adaptive advantage contributing to bacterial persistence. Considering that the presence of S. aureus in the bone microenvironment enhances osteoclastogenesis and that loss of CP is associated to chronic osteomyelitis, the aim of this study was to determine the impact of CP expression in osteoclast differentiation. We determined the ability of different S. aureus strain pairs-encapsulated (CP5+) and nonencapsulated (NT) - to induce osteoclast differentiation using RAW 264.7 cells as precursors. The S. aureus Reynolds strain CP5+ induced significantly decreased osteoclastogenesis than its genetically obtained NT derivative (p<0.05, Student t test). Equivalent results were obtained using a clinical isolate. The S. aureus NT isolate HU14, obtained from a patient with chronic osteomyelitis, induced significantly increased osteoclastogenesis than its CP5+ derivative P3.1 (p<0.05, Student t test). In addition, we analyzed the production of TNF-alpha, a pro-inflammatory cytokine known to positively modulate osteoclastogenesis. Regardless of the S. aureus pair evaluated, the NT isolates induced higher levels of TNF-alpha (p<0.05, Student t test) in osteoclast precursors, than their related CP5+ positive derivatives. Taken together, these results suggest that the loss of capsular polysaccharide expression contributes to enhance inflammatory signaling and osteoclastogenesis representing an adaptive advantage for S. aureus during chronic bone infection.