title: Complement c5a generation by staphylococcal biofilms.
abstract: Biofilms production is a central feature of nosocomial infection of catheters and other medical devices used in resuscitation and critical care. However, the very effective biofilm forming pathogen Staphylococcus epidermidis often produces a modest host inflammatory response and few of the signs and symptoms associated with more virulent pathogens. To examine the impact of bacterial biofilm formation on provocation of an innate immune response, we studied the elaboration of the major complement anaphylatoxin C5a by human serum upon contact with S. epidermidis biofilms. Wild-type S. epidermidis and mutants of sarA (a regulatory protein that promotes synthesis of the biofilm-forming polysaccharide intercellular adhesin [PIA]) and icaB (responsible for postexport processing of PIA) were studied. C5a release, as a function of exposed biofilm surface area, was on the order of 1 fmol · cm · s and was dependent on the presence of PIA. Experimental results were used to inform a physiologically based pharmacokinetic model of C5a release by an infected central venous catheter, one of S. epidermidis' primary means of causing human disease. These simulations revealed that the magnitude of C5a release on a superior vena cava catheter completely covered with S. epidermidis would be lower than necessary to alert circulating leukocytes. Combined, the experimental and computational results are highly consistent with clinical observations in which the clinical signs of central line-associated bloodstream infection are often muted in association with this important pathogen.
authors: Department of Emergency Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors: Ashley E
authors: AE
authors: Satorius
authors: Jacob
authors: J
authors: Szafranski
authors: Derek
authors: D
authors: Pyne
authors: Mahesh
authors: M
authors: Ganesan
authors: Michael J
authors: MJ
authors: Solomon
authors: Duane W
authors: DW
authors: Newton
authors: David M
authors: DM
authors: Bortz
authors: John G
authors: JG
authors: Younger
mesh_terms: D000581:Amidohydrolases / Q000502:physiology; D016470:Bacteremia / Q000276:immunology; D001426:Bacterial Proteins / Q000502:physiology; D018441:Biofilms; D062905:Central Venous Catheters / Q000382:microbiology; D015936:Complement C5a / Q000096:biosynthesis* / Q000276:immunology; D004866:Equipment Contamination; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D008954:Models, Biological; D011135:Polysaccharides, Bacterial / Q000502:physiology; D013203:Staphylococcal Infections / Q000276:immunology; D013212:Staphylococcus epidermidis / Q000276:immunology*; D015534:Trans-Activators / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; D011135:Polysaccharides, Bacterial; C088021:SarA protein, bacterial; D015534:Trans-Activators; C113579:polysaccharide intercellular adhesin; D015936:Complement C5a; D000581:Amidohydrolases; C497363:poly-N-acetylglucosamine deacetylase