<i>Streptococcus mutans</i> PrsA mediates AtlA secretion contributing to extracellular DNA release and biofilm formation in the pathogenesis of infective endocarditis

Abstract

The role of secretion chaperone-regulated virulence proteins in the pathogenesis of infective endocarditis (IE) induced by viridans streptococci such as <i>Streptococcus mutans</i> is unclear. In this study, we investigated the contribution of the foldase protein PrsA, a putative parvulin-type peptidyl-prolyl isomerase, to the pathogenesis of <i>S. mutans</i>-induced IE. We found that a <i>prsA</i>-deficient strain had reduced virulence in terms of formation of vegetation on damaged heart valves, as well as reduced autolysis activity, eDNA release and biofilm formation capacity. The secretion and surface exposure of AtlA <i>in vitro</i> was reduced in the <i>prsA</i>-deficient mutant strain, and complementation of recombinant AtlA in the culture medium restored a wild type biofilm phenotype of the <i>prsA</i>-deficient mutant strain. This result suggests that secretion and surface localization of AtlA is regulated by PrsA during biofilm formation. Together, these results demonstrate that <i>S. mutans</i> PrsA could regulate AtlA-mediated eDNA release to contribute to biofilm formation in the pathogenesis of IE.