TY - JOUR
T1 - A serine-rich glycoprotein of Streptococcus sanguis mediates adhesion to platelets via GPIb
AU - Plummer, Christopher
AU - Wu, Hui
AU - Kerrigan, Steven W.
AU - Meade, Gerardene
AU - Cox, Dermot
AU - Douglas, C. W.Ian
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2005/4
Y1 - 2005/4
N2 - 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.
AB - 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.
KW - Glycoprotein Ib
KW - Infective endocarditis
KW - Platelet adhesion
KW - Streptococcus sanguis
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U2 - 10.1111/j.1365-2141.2005.05421.x
DO - 10.1111/j.1365-2141.2005.05421.x
M3 - Article
C2 - 15801962
AN - SCOPUS:17144431888
SN - 0007-1048
VL - 129
SP - 101
EP - 109
JO - British Journal of Haematology
JF - British Journal of Haematology
IS - 1
ER -