title: Effects of polysaccharide intercellular adhesin (PIA) in an ex vivo model of whole blood killing and in prosthetic joint infection (PJI): A role for C5a.
abstract: BACKGROUND
  A major complication of using medical devices is the development of biofilm-associated infection caused by Staphylococcus epidermidis where polysaccharide intercellular adhesin (PIA) is a major mechanism of biofilm accumulation. PIA affects innate and humoral immunity in isolated cells and animal models. Few studies have examined these effects in prosthetic joint infection (PJI).
  
  
  METHODS
  This study used ex vivo whole blood modelling in controls together with matched-serum and staphylococcal isolates from patients with PJI.
  
  
  RESULTS
  Whole blood killing of PIA positive S. epidermidis and its isogenic negative mutant was identical. Differences were unmasked in immunosuppressed whole blood pre-treated with dexamethasone where PIA positive bacteria showed a more resistant phenotype. PIA expression was identified in three unique patterns associated with bacteria and leukocytes, implicating a soluble form of PIA. Purified PIA reduced whole blood killing while increasing C5a levels. In clinically relevant staphylococcal isolates and serum samples from PJI patients; firstly complement C5a was increased 3-fold compared to controls; secondly, the C5a levels were significantly higher in serum from PJI patients whose isolates preferentially formed PIA-associated biofilms.
  
  
  CONCLUSIONS
  These data demonstrate for the first time that the biological effects of PIA are mediated through C5a in patients with PJI.
authors.affiliation: Institute of Life Science, Microbiology and Infectious Disease, Swansea University, First Floor, Room 137, Singleton Park SA2 8PP, United Kingdom.
authors.forename: Rand
authors.initials: R
authors.lastname: Al-Ishaq
authors.affiliation: Institute of Life Science, Microbiology and Infectious Disease, Swansea University, First Floor, Room 137, Singleton Park SA2 8PP, United Kingdom.
authors.forename: Jayne
authors.initials: J
authors.lastname: Armstrong
authors.affiliation: Institute of Life Science, Microbiology and Infectious Disease, Swansea University, First Floor, Room 137, Singleton Park SA2 8PP, United Kingdom.
authors.forename: Martin
authors.initials: M
authors.lastname: Gregory
authors.affiliation: Institute of Life Science, Microbiology and Infectious Disease, Swansea University, First Floor, Room 137, Singleton Park SA2 8PP, United Kingdom.
authors.forename: Miriam
authors.initials: M
authors.lastname: O'Hara
authors.affiliation: Institute of Life Science, Microbiology and Infectious Disease, Swansea University, First Floor, Room 137, Singleton Park SA2 8PP, United Kingdom.
authors.forename: Kudzai
authors.initials: K
authors.lastname: Phiri
authors.affiliation: Institute of Life Science, Microbiology and Infectious Disease, Swansea University, First Floor, Room 137, Singleton Park SA2 8PP, United Kingdom.
authors.forename: Llinos G
authors.initials: LG
authors.lastname: Harris
authors.affiliation: Institut für Medizinische Mikrobiologie, Virologie und Hygiene, Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Rohde
authors.affiliation: Institut für Medizinische Mikrobiologie, Virologie und Hygiene, Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
authors.forename: Nicolaus
authors.initials: N
authors.lastname: Siemssen
authors.affiliation: Institut für Medizinische Mikrobiologie, Virologie und Hygiene, Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Frommelt
authors.affiliation: Institute of Life Science, Microbiology and Infectious Disease, Swansea University, First Floor, Room 137, Singleton Park SA2 8PP, United Kingdom; Bioscientia Labor Ingelheim, Institut für Medizinische Diagnostik GmbH, Mikrobiologie Konrad-Adenauer-Straße 17, 55218 Ingelheim, Germany.
authors.forename: Dietrich
authors.initials: D
authors.lastname: Mack
authors.affiliation: Institute of Life Science, Microbiology and Infectious Disease, Swansea University, First Floor, Room 137, Singleton Park SA2 8PP, United Kingdom. Electronic address: t.s.wilkinson@swansea.ac.uk.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Wilkinson
mesh_terms: D001168:Arthritis / Q000382:microbiology*; D001770:Blood Bactericidal Activity; D015936:Complement C5a / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D011135:Polysaccharides, Bacterial / Q000378:metabolism*; D016459:Prosthesis-Related Infections / Q000382:microbiology*; D013212:Staphylococcus epidermidis / Q000254:growth & development / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology*
chemical_list: D011135:Polysaccharides, Bacterial; C113579:polysaccharide intercellular adhesin; D015936:Complement C5a
keywords: Biofilm; Complement C5a; Polysaccharide intercellular adhesin; Prosthetic joint infection; Staphylococcus epidermidis; Whole blood