INVASION & ADHESION OF PERIOPATHOGENS

牙周病是口腔感染，导致炎症， 牙龈、牙槽骨流失以及最终的牙齿缺失。 那里 有压倒性的证据表明这些感染是由特定的 微生物，特别是革兰氏阴性细菌。 1989年 牙龈拟杆菌会议录共识报告 最常被牵连。 多种致病机制 和毒力因子与围产期疾病有关 这些生物的潜力。 然而，目前没有 就实际机制达成协议或甚至协商一致， 致病性或毒力因子。 牙周病的特点是高度急性炎症 毁灭之后是沉寂 是我们 假设Aa侵入上皮细胞并最终 结缔组织是一种毒力因子， 牙周炎的周期性特征。 细胞内 微生物可以作为细菌繁殖的宿主 牙周治疗后龈下牙根面的变化。 我们最近 开发了一种体外细胞侵袭模型， 侵入口腔上皮细胞。 粗糙的光滑同基因变体 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， 毒力因子 我们现在能够理解 粘附和侵袭的分子生物学因素 上皮细胞Aa。 拟议研究的具体目标是：1）开发 Aa粘附和侵袭因子的分子分析工具; 2)确定与Aa粘附有关的细菌因子， 在宿主细胞内的进入和定位; 3）确定 细胞内存活和增殖的内化Aa，和 Aa的释放机制。 4)确定Aa的分子基础 通过克隆粘附和侵袭基因， 确定参与粘附和侵袭表型的基因座 通过TnphoA诱变;测序克隆的基因;和纯化 表达的蛋白质。 4)结构侵袭和粘连减 通过野生型基因与 变异的克隆基因 我们的长期目标是了解 Aa利用的粘附和侵入过程，并获得一些 关于粘附和侵袭在肿瘤中的重要性， 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.