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Published on: May 19, 2020
Staphylococcus epidermidis polysaccharide intercellular adhesin activates complement
Elizabeth G Aarag Fredheim1, Hildegunn Norbakken Granslo, Trond Flægstad
1Paediatric Research Group, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway. elizabeth.aarag@uit.no
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.
Insights
Staphylococcus epidermidis polysaccharide intercellular adhesin (PIA) strongly activates the complement system, contributing to inflammation. However, PIA biofilms may hinder immune cell activation, potentially aiding bacterial survival.
Area of Science:
- Microbiology
- Immunology
- Infectious Diseases
Background:
- Staphylococcus epidermidis is a major cause of hospital-acquired infections.
- Biofilm formation, mediated by polysaccharide intercellular adhesin (PIA), is a key virulence factor.
- PIA and biofilms are linked to immune evasion strategies.
Purpose of the Study:
- To investigate the impact of S. epidermidis PIA on the host inflammatory response.
- To specifically examine the role of PIA in complement activation.
- To compare the immune-modulating effects of PIA-positive and PIA-negative S. epidermidis strains.
Main Methods:
- Utilized a human whole-blood ex vivo infection model.
- Compared a PIA-positive strain (SE1457) with its PIA-negative isogenic mutant (M10).
- Investigated the independent effect of purified PIA on complement activation.
Main Results:
- SE1457 formed a PIA-rich biofilm, while the mutant formed a proteinaceous, DNA-rich biofilm.
- PIA-positive strain induced stronger complement system activation compared to the mutant.
- Purified PIA independently triggered significant complement activation.
- The PIA-negative mutant induced greater granulocyte activation (CD11b) and cytokine secretion.
Conclusions:
- S. epidermidis PIA possesses potent pro-inflammatory properties via complement activation.
- The reduced granulocyte and cytokine activation by PIA biofilms may impede bacterial clearance.
- A complex interplay exists between PIA-mediated complement activation and other immune responses in S. epidermidis infections.
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