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.

莫拉氏菌Catarrhalis是一种革兰氏阴性的人类病原体，主要导致中耳 婴儿和儿童的感染和鼻窦炎，以及成人的下呼吸道感染。这个有机体 是中耳炎的第三个主要原因，据估计，大约50％的儿童将成为 在生命的前6个月被该细菌殖民。复发性急性中耳炎培养基也有 普遍存在导致潜在的听力损失以及随后的发展和学习问题 随着这些孩子达到学龄的年龄。中耳感染非常普遍，估计有80％ 3岁以下的儿童将至少经历一集。也有巨大的医疗保健费用 与中耳炎的治疗相关，并且已经确定Cartarrhalis M. 每年大约3至400万医师办公室访问。该估计现在被认为是保守的 超过90％的卡塔哈里菌临床分离株产生了β-内酰胺酶。这些数据在一起 旨在识别殖民化和涉及的特定毒力因素的刺激研究工作 感染。在2000年NIDCD赞助的中耳炎媒体研讨会上，小组强调了需要 更多的研究工作致力于鉴定细菌定植因素和鉴定 新的疫苗和治疗靶标。在此提案中，我们描述了 与Cartarrhalis pili的生物合成和组装有关的基因。迄今这些结构 被完全忽略了推定的定植因素。我们在此应用程序中提供的数据 证明我们已经确定了与IV型pili基因同源的多个Cartarrhalis基因 （TFP）为其他重要的革兰氏阴性人病原体所描述的系统。我们的研究表明pili 表达在遗传和表型水平上都是保守的。我们假设pili表达是 在定植的早期阶段的基本组成部分，因此这些结构可能是重要的目标 对于人类的免疫反应。该提案的具体目的是：1）隔离和表征 Cartarhalis pili的生物合成，组装，挤出和缩回的基因。 2）评估Cartarrhalis pili M. pili在定植和发病机理中的功能，并表征抗体 对Pila和Pilq的回应。