Staphylococcus epidermidis polysaccharide intercellular adhesin activates complement

Abstract

Staphylococcus epidermidis is a frequent cause of nosocomial infections. The central virulence factor of S. epidermidis is biofilm formation. Polysaccharide intercellular adhesin (PIA) constitutes the major biofilm matrix-component. PIA and biofilm have been implicated in S. epidermidis evasion of host immune defence. We examined the effects of S. epidermidis PIA on the inflammatory response with focus on complement activation. We used a human whole-blood ex vivo model of infection and compared the effects of a PIA-positive S. epidermidis strain (SE1457) and its PIA-negative isogenic mutant (M10). The independent effect of purified PIA on complement activation was investigated. In glucose-rich media, the mutant formed a proteinacious DNA-rich biofilm, whereas SE1457 formed a thick PIA-biofilm. In biofilm growth, SE1457 induced a stronger activation of the complement system compared with M10. We verified that purified PIA was independently responsible for a strong activation of the complement system. In contrast, M10 induced higher granulocyte activation by expression of CD11b and higher secretion of cytokines. We conclude that PIA has potent pro-inflammatory properties by activating the complement system. However, in a complex balance of the immune response, the decreased activation of granulocytes and cytokines by a PIA biofilm may limit host eradication of S. epidermidis.

Staphylococcus epidermidis biofilms induce lower complement activation in neonates as compared with adults

“…A lower activity of the alternative amplification loop may also explain why we observed lower levels of activation products of the final common pathway in cord blood. We have previously shown that PIA biofilm and purified PIA induced a strong complement activation (23). Similar findings were observed in the current study.…”

“…The PIA biofilm induced markedly stronger complement activation than the non-PIA biofilm, both in adult and cord blood. Collectively, these data support our hypothesis that PIA is a complement activator (10,23) in neonates as well.…”

“…The substantial activation in the alternative pathway probably reflects an activation of the alternative amplification loop (24,25). In a previous study, we found the same pattern of complement activation in adults (23).…”

“…Previous studies in adults have suggested that the complement system is important in fighting biofilm-associated SE infections (10,23). We found lower complement activation in the cord blood as compared with adult blood but a more powerful secretion of early proinflammatory cytokines.…”

“…We have previously shown that SE biofilms induce a strong complement response in blood from healthy adults (23), indicating a putative important role of the complement cascade in SE infections. To our knowledge, no previous studies have analyzed the complement response to SE biofilms in neonates.…”