title: Amino acid alterations in fibronectin binding protein A (FnBPA) and bacterial genotype are associated with cardiac device related infection in Staphylococcus aureus bacteraemia.
abstract: OBJECTIVE
  Staphylococcus aureus initiates cardiac device-related infection (CDI) by binding of fibronectin binding protein A (FnBPA) to the device's surface. In FnBPA, specific "binding enhancing" amino acid alterations are associated with CDI. However, no study has investigated whether these mutations also occur in geographically different regions and whether they arise during infection or are inherent properties of the infecting isolate.
  
  
  METHODS
  We analysed bacterial isolates from 34 patients with S. aureus bacteraemia and implanted cardiac devices for association with CDI, FnBPA sequence, classification into a clonal complex (CC), and binding to fibronectin (Fn).
  
  
  RESULTS
  We confirmed that amino acid alterations at positions 652, 782, and 786 in FnBPA were associated with CDI (p = 0.005). Furthermore, CC15 and CC45 isolates were associated with CDI (p = 0.004). All isolates within a CC exhibited a characteristic mutation pattern, with major changes occurring in CC45 including a duplication of D1 and an altered immunogenic epitope in the D3 repeat. Isolates harbouring the "binding enhancing" mutations showed a slightly increased Fn binding capability, whereas Fn binding was decreased in CC45 isolates, according to a microtiter plate assay.
  
  
  CONCLUSIONS
  FnBPA sequence variations are lineage specific and display inherent properties of the infecting isolate. Sequence analysis of FnBPA, as well as the bacterial genotype, may be used to predict the risk for device-related infection.
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Germany.
authors.forename: Nina J
authors.initials: NJ
authors.lastname: Hos
authors.affiliation: Center for Infectious Diseases and Travel Medicine, Department of Medicine, University Hospital of Freiburg, Germany.
authors.forename: Siegbert
authors.initials: S
authors.lastname: Rieg
authors.affiliation: Center for Infectious Diseases and Travel Medicine, Department of Medicine, University Hospital of Freiburg, Germany.
authors.forename: Winfried V
authors.initials: WV
authors.lastname: Kern
authors.affiliation: Department of Environmental Health Sciences, University Hospital of Freiburg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Jonas
authors.affiliation: Department of Medicine, Duke University, Durham, NC, USA.
authors.forename: Vance G
authors.initials: VG
authors.lastname: Fowler
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Germany.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Higgins
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Germany; German Centre for Infection Research (DZIF), Bonn-Cologne, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Seifert
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Germany. Electronic address: achim.kaasch@uk-koeln.de.
authors.forename: Achim J
authors.initials: AJ
authors.lastname: Kaasch
mesh_terms: D018829:Adhesins, Bacterial / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D016470:Bacteremia / Q000453:epidemiology / Q000382:microbiology*; D017147:Defibrillators, Implantable / Q000009:adverse effects; D006801:Humans; D008969:Molecular Sequence Data; D010138:Pacemaker, Artificial / Q000009:adverse effects*; D016459:Prosthesis-Related Infections / Q000453:epidemiology / Q000382:microbiology*; D013203:Staphylococcal Infections / Q000453:epidemiology / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D018829:Adhesins, Bacterial; C078635:fibronectin-binding proteins, bacterial
keywords: Clonal complex (CC); Pacemaker; Staphylococcus aureus bloodstream infection