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  • Title: Differential kinetics and molecular recognition mechanisms involved in early versus late growth phase Staphylococcus aureus cell binding to platelet layers under physiological shear conditions.
    Author: George NP, Konstantopoulos K, Ross JM.
    Journal: J Infect Dis; 2007 Aug 15; 196(4):639-46. PubMed ID: 17624852.
    Abstract:
    BACKGROUND: Staphylococcus aureus adhesion to platelets via microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) is a critical first step in vascular infection. The molecular mechanisms governing adhesion are influenced by the repertoire of MSCRAMMs expressed on the bacterial surface and the fluid mechanical shear rates present in the vasculature. We compared the predominant adhesion mechanisms between early and late growth phase S. aureus under physiological shear conditions. METHODS: A parallel-plate flow chamber was used to quantify the adhesion of early and late growth phase S. aureus to immobilized platelet layers as a function of wall shear rate. Specifically, we evaluated the influence of clumping factor (Clf) A, ClfB, serine-aspartate repeats, fibronectin-binding proteins (Fnbps), and protein A in supporting S. aureus adhesion to platelets. The ability of the plasma proteins fibrinogen and fibronectin to act as bridging molecules was also investigated. RESULTS: Our results demonstrate a markedly elevated binding efficiency for late growth phase staphylococci to immobilized platelets, compared with that of the early growth phase cells in the high shear regime. During the late growth phase, fibrinogen in concert with von Willebrand factor (vWF) potentiates S. aureus-platelet binding via shear-dependent mechanisms. By contrast, fibrinogen, but not vWF, supports the adhesion of early growth phase S. aureus at the high wall shear rates. During the early growth phase, ClfA is identified as the dominant staphylococcal adhesion receptor, with Fnbps playing a supporting role. CONCLUSION: The results presented here demonstrate a differential mechanism and binding efficiency for the adhesion of early versus late growth phase S. aureus to immobilized platelets.
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