Direct interaction of iron-regulated surface determinant IsdB of Staphylococcus aureus with the GPIIb/IIIa receptor on platelets.
The interaction of bacteria with platelets is implicated in the pathogenesis of endovascular infections, including infective endocarditis, of which Staphylococcus aureus is the leading cause. Several S. aureus surface proteins mediate aggregation of platelets by fibrinogen- or fibronectin-dependent processes, which also requires specific antibodies. In this study S. aureus was grown in iron-limited medium to mimic in vivo conditions in which iron is unavailable to pathogens. Under such conditions, a S. aureus mutant lacking the known platelet-activating surface proteins adhered directly to platelets in the absence of plasma proteins and triggered aggregation. Platelet adhesion and aggregation was prevented by inhibiting expression of iron-regulated surface determinant (Isd) proteins. Mutants defective in IsdB, but not IsdA or IsdH, were unable to adhere to or aggregate platelets. Antibodies to the platelet integrin GPIIb/IIIa inhibited platelet adhesion by IsdB-expressing strains, as did antagonists of GPIIb/IIIa. Surface plasmon resonance demonstrated that recombinant IsdB interacts directly with GPIIb/IIIa.
Miajlovic
Helen
H
Department of Microbiology, Moyne Institute of Preventive Medicine, Trinity College Dublin, Dublin 2, Ireland.
Zapotoczna
Marta
M
Department of Microbiology, Moyne Institute of Preventive Medicine, Trinity College Dublin, Dublin 2, Ireland.
Geoghegan
Joan A
JA
Department of Microbiology, Moyne Institute of Preventive Medicine, Trinity College Dublin, Dublin 2, Ireland.
Kerrigan
Steven W
SW
Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
Speziale
Pietro
P
Department of Biochemistry, Viale Taramelli 3/b,27100 Pavia, Italy.
Foster
Timothy J
TJ
Department of Microbiology, Moyne Institute of Preventive Medicine, Trinity College Dublin, Dublin 2, Ireland.
D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001792:Blood Platelets / Q000382:microbiology*; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D003165:Complement System Proteins / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D009154:Mutation; D010973:Platelet Adhesiveness; D010974:Platelet Aggregation; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*; D053657:Platelet-Rich Plasma; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013211:Staphylococcus aureus / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D020349:Surface Plasmon Resonance
D001426:Bacterial Proteins; D027682:Cation Transport Proteins; D007074:Immunoglobulin G; C510010:IsdB protein, Staphylococcus aureus; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011994:Recombinant Proteins; D003165:Complement System Proteins; D007501:Iron