The role of Staphylococcus aureus adhesins in the pathogenesis of ventricular assist device-related infections.
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.
Division of Infectious Diseases, Department of Medicine, Columbia University, New York, New York 10032, USA.
Carlos
C
Arrecubieta
Tomohiro
T
Asai
Manuel
M
Bayern
Anthony
A
Loughman
J Ross
JR
Fitzgerald
Corbett E
CE
Shelton
Helen M
HM
Baron
Nicholas C
NC
Dang
Mario C
MC
Deng
Yoshifumi
Y
Naka
Timothy J
TJ
Foster
Franklin D
FD
Lowy
D018829:Adhesins, Bacterial / Q000302:isolation & purification / Q000502:physiology*; D000818:Animals; D000907:Antibodies, Bacterial / Q000378:metabolism; D003030:Coagulase / Q000302:isolation & purification / Q000502:physiology*; D004195:Disease Models, Animal; D006353:Heart-Assist Devices / Q000009:adverse effects / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning / Q000379:methods; D010957:Plasmids; D011140:Polyurethanes / Q000378:metabolism; D016459:Prosthesis-Related Infections / Q000209:etiology* / Q000382:microbiology; D013203:Staphylococcal Infections / Q000209:etiology* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000502:physiology*; D013997:Time Factors
D018829:Adhesins, Bacterial; D000907:Antibodies, Bacterial; D003030:Coagulase; D011140:Polyurethanes; C078635:fibronectin-binding proteins, bacterial