A serine-rich glycoprotein of Streptococcus sanguis mediates adhesion to platelets via GPIb.
Streptococcus sanguis is the most common oral bacterium causing infective endocarditis and its ability to adhere to platelets, leading to their activation and aggregation, is thought to be an important virulent factor. Previous work has shown that S. sanguis can bind directly to platelet glycoprotein (GP) Ib but the nature of the adhesin was unknown. Here, we have shown that a high molecular weight glycoprotein of S. sanguis mediates adhesion to glycocalacin. The bacterial glycoprotein was purified from cell extracts by chromatography on GPIb- and wheatgerm agglutinin affinity matrices and its interaction with GPIb was shown to be sialic acid-dependent. We designated the glycoprotein serine-rich protein A (SrpA). An insertional inactivation mutant lacking the SrpA of S. sanguis showed significantly reduced binding to glycocalacin, reduced adherence to platelets and a prolonged lag time to platelet aggregation. In addition, under flow conditions, platelets rolled and subsequently adhered on films of wild-type S. sanguis cells at low shear (50/s) but did not bind to films of the SrpA mutant. Platelets did not bind to wild-type bacterial cells at high shear (1500/s). These findings help to understand the mechanisms by which the organism might colonize platelet-fibrin vegetations.
Plummer
Christopher
C
Department of Oral Pathology, School of Clinical Dentistry, University of Sheffield, Sheffield, UK.
Wu
Hui
H
Kerrigan
Steven W
SW
Meade
Gerardene
G
Cox
Dermot
D
Ian Douglas
C W
CW
D000328:Adult; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D015153:Blotting, Western; D004305:Dose-Response Relationship, Drug; D006023:Glycoproteins / Q000235:genetics / Q000502:physiology; D006801:Humans; D016254:Mutagenesis, Insertional; D019158:N-Acetylneuraminic Acid / Q000494:pharmacology; D010973:Platelet Adhesiveness / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D010974:Platelet Aggregation / Q000235:genetics / Q000502:physiology; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism*; D013298:Streptococcus sanguis / Q000235:genetics / Q000378:metabolism*
D001426:Bacterial Proteins; D006023:Glycoproteins; D019038:Platelet Glycoprotein GPIb-IX Complex; C023592:glycocalicin; C501626:serine-rich glycoprotein A, Streptococcus sanguis; D019158:N-Acetylneuraminic Acid