INVASION & ADHESION OF PERIOPATHOGENS

牙周病是一种口腔感染，会导致牙周炎 牙龈，牙槽骨丢失，最终牙齿脱落。那里 有确凿的证据表明这些感染是由特定的 微生物，尤其是革兰氏阴性细菌。1989年的 牙龈类杆菌会议论文集的共识报告 涉案最多的是。多种致病机制 毒力因子与围产期疾病有关 这些有机体的潜力。然而，目前还没有 就实际机制达成一致，甚至达成共识 这些生物体中的致病因素或毒力因素。 牙周病的特点是高度急性炎症。 毁灭之后是一段时期的平静。这是我们的 假设AA侵袭上皮细胞并最终 结缔组织是一种毒力因子，在 牙周炎的周期性特征。细胞内 生物体可以作为细菌重新克隆的蓄水池。 牙周治疗后的龈下根面。我们最近 开发了一种证明再生障碍性贫血的体外细胞侵袭模型 侵入口腔上皮细胞。Rough的平滑同基因变体 表型最具侵袭性，而粗糙表型最具侵袭性 粘合剂。这些数据表明，有一个协调的监管 毒力因素。我们现在能够理解 黏附和侵袭的分子生物学相关因素 再生障碍性贫血对上皮细胞的影响。 拟议研究的具体目标是：1)开发 AA黏附和侵袭因子的分子分析工具； 2)确定与AA粘连有关的细菌因素 在宿主细胞内的进入和定位；3)确定 内化氨基酸在细胞内的存活和增殖，以及 AA的释放机制。4)确定AA的分子碱基 通过克隆黏附和侵袭基因实现黏附和侵袭； 确定与黏附和侵袭表型有关的基因座 对克隆的基因进行测序(S)；纯化 表达的蛋白质。4)构造侵袭和粘连减法 野生型基因与AA等位基因重组产生的AA突变体 突变的克隆基因。 我们的长期目标是了解 AA利用的黏附和侵袭过程，并获得一些 对粘连和侵袭的重要性的见解 牙周感染的建立。

Periodontal diseases are oral infections that lead to inflammation of the gingiva, alveolar bone loss, and eventual loss of teeth. There is overwhelming evidence that these infections are caused by specific microorganisms particularly gram negative bacteria. The 1989 consensus report of the Proceedings of the Bacteroides gingivalis were implicated most frequently. A variety of pathogenic mechanisms and virulence factors have been associated with the periopathic potential of these organisms. Currently, however, there is no agreement or even consensus as to the actual mechanisms of pathogenesis or virulence factors among these organisms. Periodontic diseases are characterized by highly acute inflammation and destruction followed by periods of quiescence. It is our hypothesis that Aa invasion of epithelial cells and eventually connective tissues is a virulence factor and plays a role in the characteristic periodicity of periodontitis. The intracellular organisms may serve as reservoirs from which the bacteria recolonize the subgingival root surfaces after periodontal therapy. We recently developed an in vitro cell invasion model that demonstrates Aa invades oral epithelial cells. Smooth isogenic variants of the rough phenotype are most invasive while the rough phenotype is most adhesive. These data suggest there is a coordinated regulation of virulence factors. We are now in a position to understand the factors involved in the molecular biology of adhesion to and invasion of epithelial cells by Aa. The specific aims of the proposed research are to 1) develop the tools for the molecular analysis of Aa adhesion and invasion factors; 2) determine the bacterial factors involved in Aa adhesion to and entry and localization within host cells; 3) determine the intracellular survival and multiplication of internalized Aa, and the mechanisms of release of Aa. 4) Determine the molecular bases for Aa adhesion and invasion by cloning the adhesion and invasion genes; determining the loci involved in the adhesion and invasion phenotype by TnphoA mutagenesis; sequencing the cloned gene(s); and purifying the expressed proteins. 4) Construct invasion and adhesion minus mutants of Aa by allelic recombination of wild-type genes with mutated cloned genes. Our long term goals are to understand the overall nature of the adhesion and invasion processes utilized by Aa and to gain some insight as to the importance of adhesion and invasion in the establishment of periodontal infection.