Enterococcus faecalis colonizes and forms persistent biofilm microcolonies on undamaged endothelial surfaces in a rabbit endovascular infection model.
Enterococcus faecalis colonizes and forms persistent biofilm microcolonies on undamaged endothelial surfaces in a rabbit endovascular infection model.
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DOI：
10.1093/femsmc/xtab014
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Dunny GM
中科院分区：
文献类型：
--
作者：
Barnes AMT;Frank KL;Dale JL;Manias DA;Powers JL;Dunny GM
感染性心内膜炎(IE)是一种发病率和死亡率都很高的罕见疾病。IE的发病机制历来被描述为一系列宿主特异性事件，始于内皮细胞损伤和血栓形成，然后是新生血栓的细菌定植。粪肠球菌是大多数陆地动物胃肠道微生物区系中的革兰氏阳性共生细菌成员，也是包括心内膜炎在内的机会性生物膜相关感染的主要原因。在此，我们提供了粪肠球菌在兔血管内感染模型中可以在不存在预先存在的损伤和没有血栓形成的情况下定植于心内膜表面的证据。利用前面描述的光学和扫描电子显微镜技术，我们发现，在新西兰白兔的耳缘静脉接种特征良好的粪肠球菌Lab株后，在给药后4天内，心内膜在整个心脏内迅速定植。出乎意料的是，超微结构成像显示，在没有大体组织损伤的形态证据的区域，微克隆直接牢固地附着在心内膜上。此外，附着的细菌聚集体与凝血或宿主细胞外基质损伤修复(即血小板)的重要细胞成分无关。这些结果表明，作为细菌附着到宿主内皮下成分的先决条件的机械表面损伤的规范模型是不必要的。此外，这些发现与初步建立稳定的、与心内膜炎相关的粪肠球菌生物被膜微克隆的模型是一致的，该微克隆可能为临床心内膜炎的最终瓣膜感染提供储备库。在这个兔血管内感染模型和我们以前发表的小鼠胃肠道定植模型中看到的粪肠球菌定植和生物膜形态之间的相似之处表明，生物膜的产生和共同的宿主细胞附着因子在不同的哺乳动物宿主中在共生和致病环境下都是保守的。粪肠球菌在未受损的兔血管内皮细胞上形成体内微集落。
Infectious endocarditis (IE) is an uncommon disease with significant morbidity and mortality. The pathogenesis of IE has historically been described as a cascade of host-specific events beginning with endothelial damage and thrombus formation and followed by bacterial colonization of the nascent thrombus. Enterococcus faecalis is a Gram-positive commensal bacterial member of the gastrointestinal tract microbiota in most terrestrial animals and a leading cause of opportunistic biofilm-associated infections, including endocarditis. Here, we provide evidence that E. faecalis can colonize the endocardial surface without pre-existing damage and in the absence of thrombus formation in a rabbit endovascular infection model. Using previously described light and scanning electron microscopy techniques, we show that inoculation of a well-characterized E. faecalis lab strain in the marginal ear vein of New Zealand White rabbits resulted in rapid colonization of the endocardium throughout the heart within 4 days of administration. Unexpectedly, ultrastructural imaging revealed that the microcolonies were firmly attached directly to the endocardium in areas without morphological evidence of gross tissue damage. Further, the attached bacterial aggregates were not associated with significant cellular components of coagulation or host extracellular matrix damage repair (i.e. platelets). These results suggest that the canonical model of mechanical surface damage as a prerequisite for bacterial attachment to host sub-endothelial components is not required. Furthermore, these findings are consistent with a model of initial establishment of stable, endocarditis-associated E. faecalis biofilm microcolonies that may provide a reservoir for the eventual valvular infection characteristic of clinical endocarditis. The similarities between the E. faecalis colonization and biofilm morphologies seen in this rabbit endovascular infection model and our previously published murine gastrointestinal colonization model indicate that biofilm production and common host cell attachment factors are conserved in disparate mammalian hosts under both commensal and pathogenic contexts. Enterococcus faecalis forms microcolonies in vivo on undamaged rabbit endovasculature.