TY - JOUR
T1 - Differential kinetics and molecular recognition mechanisms involved in early versus late growth phase Staphylococcus aureus cell binding to platelet layers under physiological shear conditions
AU - George, Niraj Procopio Evagrio
AU - Konstantopoulos, Konstantinos
AU - Ross, Julia Myers
N1 - Funding Information:
Received 8 November 2006; accepted 12 March 2007; electronically published 29 June 2007. Potential conflicts of interest: none reported. Financial support: National Institutes of Health (grant R01HL066453). Reprints or correspondence: Dr. Julia M. Ross, Dept. of Chemical and Biochemical Engineering, University of Maryland Baltimore County, 1000 Hilltop Cir., Baltimore, MD 21250 (jross@umbc.edu).
PY - 2007/8/15
Y1 - 2007/8/15
N2 - 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.
AB - 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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U2 - 10.1086/519740
DO - 10.1086/519740
M3 - Article
C2 - 17624852
AN - SCOPUS:34547619827
SN - 0022-1899
VL - 196
SP - 639
EP - 646
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 4
ER -