an-vitro-model-parallel-plate-perfusion-system-to-study-bacterial

An <em>In Vitro</em> Model of a Parallel-Plate Perfusion System to Study Bacterial Adherence to Graft Tissues

Various valved conduits and stent-mounted valves are used for right ventricular outflow tract (RVOT) valve replacement in patients with congenital heart ...

KU Leuven

Adhesion of  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, ABC, CD) to coverslip-coated vWF, Fg/fibrin, Fn or confluent ECs, making use of , expressing these adhesins heterologously. Global adherence profiles were similar in static and flow conditions. In the absence of plasma,  binding to Fg increased with shear forces, whereas binding to fibrin did not. The degree of adhesion of  to EC-bound Fn and of  to EC-bound Fg, furthermore, was similar to that of  to coated vWF domain A1, in the presence of vWF-binding protein (vWbp). Yet, in plasma,  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  likewise by > 70% compared to the adhesion in absence of plasma. In contrast, plasma Fg supported high  binding to resting and activated ECs. Or, in plasma  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.

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

Are plasma proteins key players in the pathogenesis of infective endocarditis?

Infective endocarditis (IE) remains a diagnostic and therapeutic challenge associated with high morbidity and mortality. We evaluated the microbial profile and clinical manifestation of IE in children.

Article	Year
Assessment of the Dual Role of Clumping Factor A in S. Aureus Adhesion to Endothelium in Absence and Presence of Plasma. Thrombosis and haemostasis\| PubMed ID: 29909601	2018
Are plasma proteins key players in the pathogenesis of infective endocarditis? The Journal of thoracic and cardiovascular surgery\| PubMed ID: 30011766	2018
Clinical Characteristics of Infective Endocarditis in Children. The Pediatric infectious disease journal\| PubMed ID: 30346369	2018

Bartosz Ditkowski

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