title: 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.
authors.affiliation: Paediatric Research Group, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway. elizabeth.aarag@uit.no
authors.forename: Elizabeth G Aarag
authors.initials: EG
authors.lastname: Fredheim
authors.forename: Hildegunn Norbakken
authors.initials: HN
authors.lastname: Granslo
authors.forename: Trond
authors.initials: T
authors.lastname: Flægstad
authors.forename: Yngve
authors.initials: Y
authors.lastname: Figenschau
authors.forename: Holger
authors.initials: H
authors.lastname: Rohde
authors.forename: Irina
authors.initials: I
authors.lastname: Sadovskaya
authors.forename: Tom Eirik
authors.initials: TE
authors.lastname: Mollnes
authors.forename: Claus
authors.initials: C
authors.lastname: Klingenberg
mesh_terms: D018441:Biofilms / Q000254:growth & development; D001769:Blood / Q000276:immunology / Q000382:microbiology; D003167:Complement Activation; D003165:Complement System Proteins / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D017353:Gene Deletion; D006098:Granulocytes / Q000276:immunology; D006805:Human Experimentation; D006801:Humans; D011135:Polysaccharides, Bacterial / Q000235:genetics / Q000276:immunology*; D013212:Staphylococcus epidermidis / Q000235:genetics / Q000276:immunology* / Q000502:physiology
chemical_list: D016207:Cytokines; D011135:Polysaccharides, Bacterial; C113579:polysaccharide intercellular adhesin; D003165:Complement System Proteins