INVASION AND ADHESION OF PERIOPATHOGENS

伴放线放线杆菌(Aa)为革兰氏阴性杆菌， 兼职 定植于人类口腔和上半身的球状杆菌 呼吸道。微生物、免疫学和临床研究 有 AA在成人和青少年的发病机制中有牵连 牙周炎。再生性贫血也与更严重的人类 感染，如心内膜炎和软组织脓肿。 尽管 牙周组织被认为是这些感染的来源， 小才是 了解AA用来维持自身在 口头的 空洞并在组织中渗透和扩散。 病原体已经发展出非常复杂和多样化的策略 的 宿主细胞感染和组织扩散。入侵机制 使用 对肠道致病菌进行了广泛的研究。 这个 过程包括多个步骤和无数人的参与 细菌 基因。口腔病原体的入侵还不够充分 学习。 我们的实验室提供了唯一一项关于 入侵 一种牙周病的微生物。AA入侵是一个动态过程 多步骤 包括宿主和细菌之间的串扰的过程。 AA的黏附和随后进入与宿主细胞相关 肌动蛋白 重排，可能由转铁蛋白受体介导。 出口 似乎依赖于微管结构。AA传播到 相邻的 细胞是通过宿主细胞表面突起来调节的。这些 研究 促使我们提出了一个AA入侵过程的模型。在这 提案，我们计划集中在宿主细胞如何响应 这个 再障的侵袭。 为了加深我们对关键要素的理解 AA型 发病机制，我们建议(1)评估 转铁蛋白 AA受体进入上皮细胞，(2)确立作用 的 AA细胞内扩散的微管，(3)决定 细菌的生物发生 含AA的液泡，(4)确定实时序列 活动 在侵袭过程中，以及(5)研究瞬时钙 流入的流量 入侵过程。 对AA中起关键作用的要素的理解 发病机制 应该为Rational的发展提供洞察力 化疗 牙周病治疗中的干预措施。

Actinobacillus actinomycetemcomitans (Aa) is a Gram-negative, facultative coccobacillus which colonizes the human oral cavity and the upper respiratory tract. Microbial, immunological and clinical studies have implicated Aa in the pathogenesis of both adult and juvenile periodontitis. Aa has also been associated with more serious human infections such as endocarditis and soft tissue abscesses. Although the periodontium is believed to be the source of these infections, little is known about the mechanisms used by Aa to maintain itself within the oral cavity and to infiltrate and disseminate in tissues. Pathogens have developed remarkably complex and diverse strategies of host cell infection and tissue dispersion. The invasion mechanisms used by the intestinal pathogens have been investigated extensively. The processes include multiple steps and the involvement of myriad bacterial genes. The invasion of oral pathogens has not been adequately studied. Our laboratory has provided the only extensive study on the invasion of a periodontopathic microorganism. Aa invasion is a dynamic multistep process which involves cross-talk between the host and bacterium. Adhesion and subsequent entry of Aa is correlated with host cell actin rearrangement, and is likely mediated by transferrin receptor. Exit appears to be dependent on microtubule structure. Aa spread to adjacent cells is mediated through host cell surface protrusions. These studies promoted us to propose a model of the Aa invasion process. In this proposal, we plan to concentrate on how the host cell responds to the invasion of Aa. In order to further our understanding of the critical elements of Aa pathogenesis, we propose to (1) evaluate the role of the transferrin receptor in Aa entry into epithelial cells, (2) establish the role of microtubules in Aa intracellular spread, (3) determine the biogenesis of the Aa-containing vacuole, (4) determine the real-time sequence of events in the invasion process, and (5) investigate transient calcium fluxes in the invasion process. An understanding of the elements that play key roles in Aa pathogenesis should provide insights for the development of rational chemotherapeutic interventions in the treatment of periodontal diseases.