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

资源简介：

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.

由变形链球菌（*Streptococcus mutans*）等草绿色链球菌诱导的感染性心内膜炎（infective endocarditis, IE），其发病机制中分泌伴侣调控的毒力蛋白所发挥的作用尚不清楚。本研究针对推定的parvulin型肽基脯氨酰异构酶——折叠酶蛋白PrsA，在变形链球菌诱导的IE发病机制中的作用展开探究。研究发现，prsA基因缺陷菌株在受损心脏瓣膜上形成赘生物的毒力有所减弱，同时其自溶活性、细胞外DNA（eDNA）释放能力以及生物膜形成能力均出现下降。在prsA缺陷突变株中，AtlA的体外分泌与表面暴露水平均有所降低；而在培养基中补充重组AtlA后，可恢复prsA缺陷突变株的野生型生物膜表型。该结果表明，在生物膜形成过程中，AtlA的分泌与表面定位受PrsA调控。综合以上结果，本研究证实变形链球菌PrsA可通过调控AtlA介导的eDNA释放，参与生物膜形成并在感染性心内膜炎的发病机制中发挥作用。