Biofilm Spatial Structure in the Transition from Health to Periodontal Disease

摘要 牙周病是由宿主炎症和炎症因子变化之间的动态相互作用介导的。 龈下生物膜群落组成。牙龈卟啉单胞菌是一种重要的病原体， 破坏免疫反应以促进炎症和对致病生物有利的条件， 同时抑制免疫系统清除细菌。正因为如此，牙龈卟啉单胞菌已被提议 引发牙周病。在这里，我们提出了一个新的模式，为牙周病的开始， 由长丝状细胞在牙龈边缘介导， 与上皮接触以引发牙龈炎形式的炎症。这种可逆的炎症状态 然后诱导龈下群落的生态失调。我们将通过对完整的生物膜进行成像来验证我们的假设。 用FISH技术检测牙龈炎和牙周炎的拔牙牙，包括龈缘生物膜 探测多达18种不同的分类群。我们将进一步进行定量比较结构分析， 牙周炎相关的人类生物膜和犬模型，以特异性地识别保守的结构特征 致病性龈下生物膜最后，我们将绘制差异表达基因的空间位置 在菌斑生物膜中的丝状细胞内，当这些细胞与特定伴侣直接或密切接触时， 物种这项工作将包括一个整体的方法，以确定结构功能的关系，在健康和 牙周病相关的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.