The role of Staphylococcus aureus adhesins in the pathogenesis of ventricular assist device-related infections

Carlos Arrecubieta, Tomohiro Asai, Manuel Bayern, Anthony Loughman, Ross Fitzgerald, Corbett E Shelton, Helen M Baron, Nicholas Dang, Mario C Deng, Yoshifumi Naka, Timothy J Foster, Franklin D Lowy

Research output: Contribution to journalArticlepeer-review

Abstract

Ventricular assist devices (VADs) are an important form of therapy for end-stage congestive heart failure. However, infection of the VAD, which is often caused by Staphylococcus aureus, poses a major threat to survival. Using a novel in vitro binding assay with VAD membranes and a heterologous lactococcal system of expression, we identify 3 S. aureus proteins--clumping factor A (ClfA) and fibronectin binding proteins A and B (FnBPA and FnBPB) as the main factors involved in adherence to VAD polyurethane membranes. Adherence is greatly diminished by long implantation times, reflecting a change in topological features of the VAD membrane, and is primarily mediated by the FnBPA domains in the staphylococcal proteins. We also compare the adherence of S. aureus mutant strains and show that other staphylococcal components appear to be involved in adherence to VAD membranes. Finally, we demonstrate that ClfA, FnBPA, and FnBPB mediate bacterial infection of implanted murine intra-aortic polyurethane patches.
Original languageEnglish
Pages (from-to)1109-19
Number of pages11
JournalThe Journal of Infectious Diseases
Volume193
Issue number8
DOIs
Publication statusPublished - 15 Apr 2006

Keywords

  • Adhesins, Bacterial/isolation & purification
  • Adhesins, Bacterial/physiology
  • Animals
  • Antibodies, Bacterial/metabolism
  • Coagulase/isolation & purification
  • Coagulase/physiology
  • Disease Models, Animal
  • Heart-Assist Devices/adverse effects
  • Heart-Assist Devices/microbiology
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Electron, Scanning/methods
  • Plasmids
  • Polyurethanes/metabolism
  • Prosthesis-Related Infections/etiology
  • Prosthesis-Related Infections/microbiology
  • Staphylococcal Infections/etiology
  • Staphylococcal Infections/microbiology
  • Staphylococcus aureus/physiology
  • Time Factors

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