Marginal role of von Willebrand factor-binding protein and coagulase in the initiation of endocarditis in rats with catheter-induced aortic vegetations Stefano Mancini Frank Oechslin Carmen Menzi Yok Ai Que Jorien Claes Ruth Heying Tiago Rafael Veloso Thomas Vanassche Dominique Missiakas Olaf Schneewind Philippe Moreillon José Manuel Entenza 10.6084/m9.figshare.7160423.v2 https://tandf.figshare.com/articles/journal_contribution/Marginal_Role_of_von_Willebrand_Factor-Binding_Protein_and_Coagulase_in_the_Initiation_of_Endocarditis_in_Rats_with_Catheter-Induced_Aortic_Vegetations/7160423 <p><i>Staphylococcus aureus</i> is the leading cause of infective endocarditis (IE). While the role of <i>S. aureus</i> cell-wall associated protein clumping factor A (ClfA) in promoting IE has been already demonstrated, that of the secreted plasma-clotting factors staphylocoagulase (Coa) and von Willebrand factor-binding protein (vWbp) has not yet been elucidated. We investigated the role of Coa and vWbp in IE initiation in rats with catheter-induced aortic vegetations, using <i>Lactococcus lactis</i> expressing <i>coa, vWbp, clfA</i> or <i>vWbp/clfA</i>, and <i>S. aureus</i> Newman Δ<i>coa</i>, Δ<i>vWbp</i>, Δ<i>clfA or</i> Δ<i>coa/</i>Δ<i>vWbp/</i>Δ<i>clfA</i> mutants. <i>vWbp</i>-expression increased <i>L. lactis</i> valve infection compared to parent and <i>coa</i>-expressing strains (incidence: 62%, versus 0% and 13%, respectively; <i>P </i>< 0.01). Likewise, expression of <i>clfA</i> increased <i>L. lactis</i> infectivity (incidence: 80%), which was not further affected by co-expression of <i>vWbp</i>. In symmetry, deletion of the <i>coa</i> or <i>vWbp</i> genes in <i>S. aureus</i> did not decrease infectivity (incidence: 68 and 64%, respectively) whereas deletion of <i>clfA</i> did decrease valve infection (incidence: 45%; <i>P </i>= 0.03 versus parent), which was not further affected by the triple deletion Δ<i>coa/</i>Δ<i>vWbp/</i>Δ<i>clfA</i> (incidence: 36%; <i>P </i>> 0.05 versus Δ<i>clfA</i> mutant). Coa does not support the initial colonization of IE (in <i>L. lactis</i>) without other key virulence factors and vWbp contributes to initiation of IE (in <i>L. lactis</i>) but is marginal in the present of ClfA.</p> 2018-10-13 13:36:36 Clumping factor A endocarditis staphylocoagulase Staphylococcus aureus von Willebrand factor-binding protein