Title:
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Mouth to heart : mechanisms of oral bacteria-induced platelet activation
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There has been renewed scientific interest in the role of oral bacteria in systemic disease
in recent years. The incidence of infective endocarditis (lE) in the UK has been rising
lately. Dental plaque bacteria of the genus Streptococcus are recognised causative
agents of lE. Oral Streptococcus gordonii produces several factors that are thought to be
involved in promoting lE. One of these, designated surface platelet adherence protein A
(PadA), has been only recently identified.
This study aimed to determine mechanisms by which PadA functional domains interacted
with platelets, and platelet integrin GPIIbIIIa, under static or shear conditions. The role of
PadA in platelet interactions in relation to a well-characterised platelet adhesin (Hsa) was
clarified. Furthermore, the interactions of PadA protein with extracellular matrix (ECM)
components were investigated.
This work identified PadA as a protein that binds activated platelets and confers shear
resistance. A two-step S. gordonii-platelet adherence model is proposed, whereby Hsamediated
platelet activation then enables PadA platelet adhesion and activation. This is
the result of, at least in part, the presence of an integrin-like motif NGR within PadA
binding to platelets under static conditions. PadA also binds components of the ECM
including fibronectin, vitronectin and von Willebrand factor. However, PadA-mediated
bacterial cell adherence to vitronectin and activated platelets occurs only in the presence
of Hsa. PadA and Hsa together modulate biofilm formation on salivary pellicle, but in this
case Hsa only functions in the presence of PadA. Thus it is proposed that PadA and Hsa
may form a macromolecular complex on the surface of S. gordonii. PadA-like family
proteins appear to be structurally conserved and are found in a range of lE pathogens.
Increased knowledge of the molecular interactions occurring between streptococci and
platelets will enable translation into new strategies for the prevention or treatment of
infection-associated cardiovascular diseases .
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