Assessment of the Dual Role of Clumping Factor A in S. Aureus Adhesion to Endothelium in Absence and Presence of Plasma.

Détails

ID Serval
serval:BIB_012C03C946E8
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Assessment of the Dual Role of Clumping Factor A in S. Aureus Adhesion to Endothelium in Absence and Presence of Plasma.
Périodique
Thrombosis and Haemostasis
Auteur(s)
Claes J., Ditkowski B., Liesenborghs L., Veloso T.R., Entenza J.M., Moreillon P., Vanassche T., Verhamme P., Hoylaerts M.F., Heying R.
ISSN
2567-689X (Electronic)
ISSN-L
0340-6245
Statut éditorial
Publié
Date de publication
2018
Peer-reviewed
Oui
Volume
118
Numéro
7
Pages
1230-1241
Langue
anglais
Résumé
Adhesion of <i>Staphylococcus aureus</i> to endothelial cells (ECs) is paramount in infective endocarditis. Bacterial proteins such as clumping factor A (ClfA) and fibronectin binding protein A (FnbpA) mediate adhesion to EC surface molecules and (sub)endothelial matrix proteins including fibrinogen (Fg), fibrin, fibronectin (Fn) and von Willebrand factor (vWF). We studied the influence of shear flow and plasma on the binding of ClfA and FnbpA (including its sub-domains A, A <sup>16+</sup> , ABC, CD) to coverslip-coated vWF, Fg/fibrin, Fn or confluent ECs, making use of <i>Lactococcus lactis</i> , expressing these adhesins heterologously. Global adherence profiles were similar in static and flow conditions. In the absence of plasma, <i>L. lactis-clfA</i> binding to Fg increased with shear forces, whereas binding to fibrin did not. The degree of adhesion of <i>L. lactis-fnbpA</i> to EC-bound Fn and of <i>L. lactis-clfA</i> to EC-bound Fg, furthermore, was similar to that of <i>L. lactis-clfA</i> to coated vWF domain A1, in the presence of vWF-binding protein (vWbp). Yet, in plasma, <i>L. lactis-clfA</i> adherence to activated EC-vWF/vWbp dropped over 10 minutes by 80% due to vWF-hydrolysis by a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13 and that of <i>L. lactis-fnbpA</i> likewise by > 70% compared to the adhesion in absence of plasma. In contrast, plasma Fg supported high <i>L. lactis-clfA</i> binding to resting and activated ECs. Or, in plasma <i>S. aureus</i> adhesion to active endothelium occurs mainly via two complementary pathways: a rapid but short-lived vWF/vWbp pathway and a stable integrin-coupled Fg-pathway. Hence, the pharmacological inhibition of ClfA-Fg interactions may constitute a valuable additive treatment in infective endocarditis.
Mots-clé
infective endocarditis, clumping factor A, fibronectin binding proteins, S. aureus, von Willebrand factor, fibrinogen, fibronectin
Pubmed
Web of science
Création de la notice
23/07/2018 17:23
Dernière modification de la notice
20/08/2019 13:23
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