M. catarrhalis pili: Role in Colonization.

卡他菌菌毛：在定植中的作用。

• 批准号: 7383082
• 负责人: Anthony A Campagnari
• 金额: $ 30.88万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7383082
• 关键词: Acute; Adherence; Adult; Age; Anabolism; Antibodies; Antibody Formation; Appearance; Bacteria; Bacterial Adhesins; Biological Assay; Child; Chinchilla (genus); Chronic lung disease; Clinical; Cloning; Code; Competence; Condition; Coupled; Data; Development; Educational workshop; Electron Microscopy; Fimbriae Proteins; Genes; Genetic; Health Care Costs; Heterogeneity; Human; Human Cell Line; Immune response; Infant; Infection; Laboratories; Learning; Life; Lower Respiratory Tract Infection; Lower respiratory tract structure; Microbial Biofilms; Modeling; Moraxella; Moraxella (Branhamella) catarrhalis; Office Visits; Organism; Otitis Media; Pathogenesis; Pilum; Post-Translational Protein Processing; Rate; Recurrence; Reporting; Research; Respiratory Tract Diseases; Role; School-Age Population; Sequence Analysis; Sinusitis; Staging; Structure; Surface; System; Testing; Virulence; Virulence Factors; beta-Lactamase; ear infection; experience; hearing impairment; middle ear; mutant; novel vaccines; pathogen; respiratory; ward

Moraxella catarrhalis is a Gram-negative human pathogen, which predominantly causes middle ear infections and sinusitis in infants and children, and lower respiratory tract infections in adults. This organism is the third leading cause of otitis media and it is estimated that approximately 50% of children will become colonized by this bacterium in the first 6 months of life. Recurrent acute otitis media infections have also become prevalent resulting in potential hearing loss and subsequent developmental and learning problems as these children reach school age. Middle ear infections are very common and it is estimated that 80% of children under the age of 3 will experience at least one episode. There are also significant health care costs associated with treatment for otitis media and it has been determined that M. catarrhalis is responsible for approximately 3 to 4 million physician office visits annually. This estimate is considered conservative now that over 90% of M. catarrhalis clinical isolates produce beta-lactamase. Together, these data have stimulated research efforts aimed at identifying specific virulence factors involved in colonization and infection. At the otitis media workshop sponsored by the NIDCD in 2000 the panel emphasized the need for more research efforts dedicated to the identification of bacterial colonization factors and the identification of new vaccine and treatment targets. In this proposal we describe the identification and characterization of the genes that are involved in the biosynthesis and assembly of M. catarrhalis pili. To date these structures have been totally ignored as putative colonization factors. The data we present in this application demonstrate that we have identified multiple M. catarrhalis genes with homology to genes of the type IV pili (TFP) systems described for other important gram-negative human pathogens. Our studies show that pili expression is conserved both at the genetic and phenotypic levels. We hypothesize that pili expression is an essential component in the early stages of colonization and thus these structures may be important targets for the human immune response. The specific aims of this proposal are: 1) Isolate and characterize the genes involved in the biosynthesis, assembly, extrusion and retraction of M. catarrhalis pili. 2) Evaluate the function of M. catarrhalis pili in colonization and pathogenesis and characterize the antibody response to PilA and PilQ.

卡他莫拉氏菌是一种革兰氏阴性人类病原体，主要引起中耳炎 婴儿和儿童的感染和鼻窦炎，以及成人的下呼吸道感染。这种生物体 是引起中耳炎的第三大原因，估计大约 50% 的儿童会患上中耳炎。 在生命的前 6 个月内就被这种细菌定植。急性中耳炎反复感染也 变得普遍，导致潜在的听力损失以及随后的发育和学习问题 当这些孩子达到学龄时。中耳感染非常常见，据估计 80% 3岁以下的儿童至少会经历一次发作。还有巨大的医疗保健费用 与中耳炎的治疗相关，并且已确定粘膜炎莫拉氏菌负责 每年约有 3 至 400 万人次就诊。这个估计现在被认为是保守的 超过 90% 的卡他莫拉氏菌临床分离株产生 β-内酰胺酶。这些数据加起来 刺激了旨在确定与定植有关的特定毒力因子的研究工作 感染。 2000 年，在 NIDCD 主办的中耳炎研讨会上，专家组强调需要 更多的研究工作致力于鉴定细菌定植因子和鉴定 新的疫苗和治疗目标。在本提案中，我们描述了 参与卡他菌菌毛生物合成和组装的基因。迄今为止这些结构 作为假定的殖民因素而被完全忽视。我们在此应用程序中提供的数据 证明我们已经鉴定出多个与 IV 型菌毛基因具有同源性的粘膜炎莫拉氏菌基因 (TFP) 系统描述了其他重要的革兰氏阴性人类病原体。我们的研究表明，霹雳 表达在遗传和表型水平上都是保守的。我们假设 pili 表达是 殖民早期阶段的重要组成部分，因此这些结构可能是重要目标 用于人体免疫反应。该提案的具体目标是： 1) 分离并表征 参与卡他菌菌毛生物合成、组装、挤出和收缩的基因。 2) 评估粘膜炎莫拉氏菌菌毛在定植和发病机制中的功能并表征抗体 对 PilA 和 PilQ 的响应。