Biofilm Spatial Structure in the Transition from Health to Periodontal Disease

摘要 牙周病是由宿主炎症和牙周组织改变之间的动态相互作用所介导的。 龈下生物膜群落组成。牙龈卟啉单胞菌是一种重要的致病菌。 颠覆免疫反应，促进炎症和病原体的有利条件， 同时抑制免疫系统清除细菌。正因为如此，牙龈假单胞菌被提议 引发牙周病。在这里，我们提出了一种新的牙周病发病模式， 在牙龈边缘由长丝状细胞介导，使菌斑微生物接近或直接接触 与上皮细胞接触，引发炎症，形成牙周炎。这种可逆的炎症状态 然后在牙龈下的群落中引起生物失调。我们将通过成像完整的生物膜来验证我们的假设 涉及牙周炎和牙周炎的拔牙，包括牙龈边缘的生物膜和鱼 探测多达18个不同的分类群。我们将进一步进行定量的比较结构分析 牙周炎相关的人类生物膜和犬类模型，以专门识别保守的结构特征 致病的龈下生物膜。最后，我们将绘制差异表达基因的空间位置图。 在菌斑生物膜中的丝状细胞内，当这些细胞与特定伙伴直接或密切接触时 物种。这项工作将包括一种全面的方法，以确定健康和 牙周病相关生物膜是牙周病发生和发展的基础。

ABSTRACT Periodontal disease is mediated by the dynamic interplay between host inflammation and changes in subgingival biofilm community composition. The keystone pathogen, Porphyromonas gingivalis is known to subvert the immune response to promote inflammation and favorable conditions for pathobiont organisms, while inhibiting immune system clearance of bacteria. Because of this, P. gingivalis has been proposed to initiate periodontal disease. Here we propose a new paradigm for the initiation of periodontal disease, mediated at the gingival margin by long filamentous cells that bring plaque organisms into close or direct contact with the epithelium to initiate inflammation in the form of gingivitis. This reversible inflammatory state then induces dysbiosis in the subgingival community. We will test our hypothesis by imaging intact biofilms on extracted teeth involved in gingivitis and periodontitis, including the biofilm at the gingival margin with FISH probes for up to 18 different taxa. We will further perform quantitative comparative structural analyses of periodontitis associated human biofilms and canine models to specifically identify conserved structural features of pathogenic subgingival biofilms. Lastly, we will map the spatial location of differentially expressed genes within filamentous cells in plaque biofilms when these cells are in direct or close contact with specific partner species. This work will comprise a holistic approach to identify structure-function relationships in healthy and periodontal disease-associated biofilms that underly periodontal disease initiation and progression.