P GINGIVALIS GENES INVOLVED IN EPITHELIAL ATTACHMENT

参与上皮附着的 P Gingivalis 基因

• 批准号: 2749324
• 负责人: Margaret J Duncan
• 金额: $ 27.22万
• 依托单位: ADA FORSYTH INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-01 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2749324
• 关键词: Bacteroides gingivalis; adhesin; bacterial genetics; binding proteins; cell adhesion; electron microscopy; enzyme activity; epithelium; gene deletion mutation; genetic library; molecular cloning; mutant; northern blottings; pilus; protease inhibitor; protein structure function; tissue /cell culture; transposon /insertion element; virulence; western blottings

DESCRIPTION (Adapted from the Applicant's Abstract): The diseases collectively known as periodontitis are bacterial infections. A small group of gram-negative oral bacteria are consistently associated with specific forms of disease. The presence of P. gingivalis is linked to chronic and severe adult periodontitis. P. gingivalis and the other periodontal pathogens are observed within diseased human gingiva, but the molecular mechanisms of attachment to, and penetration of, tissue are unknown. Previously, the applicant demonstrated, with quantitative data, that P. gingivalis attached to and invaded oral epithelial cells. A subsequent study showed that this organism was able to penetrate and divide within the cells of a multilayered pocket epithelium model. The current goal is to dissect the molecular events in the initial interactions between the bacterium and epithelial cells. This application focuses on the molecular mechanisms of attachment of P. gingivalis to epithelial cells. New data are presented on the in vitro modulation of attachment using P. gingivalis wild type and mutant strains. Data is also presented on P. gingivalis genes isolated after screening an expression library for clones which bound epithelial cells. The specific aims of this application are to: 1) determine the P. gingivalis activities required for attachment to epithelial cells in vitro; 2) identify the bacterial genes involved in attachment; and 3) isolate P. gingivalis isogenic mutants defective in these genes. The cross-talk between P. gingivalis and the epithelial cell takes place at the attachment step, and the infection pathway is decided, in part, by the signaling between the two cell types. Therefore, attachment is the key target for preventative intervention strategies and understanding the molecular mechanisms of attachment is critical for the development of successful therapies.

描述(改编自申请者的摘要)：疾病 统称为牙周炎的是细菌感染。一小群人 革兰氏阴性口腔细菌的持续存在与特定的 疾病的形式。牙龈假单胞菌的存在与慢性和 严重的成人牙周炎。牙龈假单胞菌和其他牙周组织 在患病的人牙龈中观察到病原体，但分子 附着和穿透组织的机制尚不清楚。 在此之前，申请人用定量数据证明了P. 牙龈附着并侵袭口腔上皮细胞。后续的 研究表明，这种微生物能够穿透并在体内分裂 多层袋上皮模型的细胞。目前的目标是 剖析了分子事件在初始相互作用中的作用 细菌和上皮细胞。这一应用主要集中在分子 牙龈假单胞菌附着于上皮细胞的机制。新的数据是 牙龈假单胞菌对附着的体外调控研究进展 模式菌株和突变菌株。此外，还提供了有关牙龈假单胞菌基因的数据。 筛选结合的克隆的表达文库后分离 上皮细胞。本申请的具体目的是：1) 测定牙龈假单胞菌附着上皮细胞所需的活性 细胞；2)确定与附着有关的细菌基因；以及 3)分离出这些基因缺陷的牙龈假单胞菌等基因突变株。这个 牙龈假单胞菌和上皮细胞之间的相互作用发生在 连接步骤，而感染途径部分地由 两种细胞类型之间的信号传递。因此，依恋是关键 预防性干预战略的目标和理解 依恋的分子机制对儿童精神分裂症的发生发展至关重要 成功的治疗方法。