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.

卡他莫拉菌是一种革兰氏阴性的人类病原体，主要引起中耳炎 感染和鼻窦炎，以及成人的下呼吸道感染。这种生物 是中耳炎的第三大主要原因，据估计，大约50%的儿童将成为 在出生后的头六个月里被这种细菌占据。复发性急性中耳炎感染也 变得普遍，导致潜在的听力损失和随后的发育和学习问题 当这些孩子到了上学的年龄。中耳炎非常常见，据估计，80%的 3岁以下的儿童将经历至少一次发作。此外，还有大量的医疗保健费用 与中耳炎的治疗相关，并且已经确定M.卡他炎是负责 每年约有300万至400万人次就诊。这个估计现在被认为是保守的 超过90%的M。卡他炎临床分离株产生β-内酰胺酶。总的来说，这些数据 刺激研究工作，旨在确定涉及定植的特定毒力因子， 感染在2000年由NIDCD主办的中耳炎研讨会上，小组强调需要 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。在该提案中，我们描述了 参与M.卡他皮利。为了确定这些建筑的年代 被认为是殖民因素而被完全忽略了。我们在此应用程序中提供的数据 证明我们已经识别了多个M。与IV型皮利基因同源的卡他基因 (TFP)其他重要的革兰氏阴性人类病原体描述的系统。我们的研究表明，皮利 表达在遗传和表型水平上都是保守的。我们假设皮利的表达是一个 在殖民化的早期阶段的重要组成部分，因此这些结构可能是重要的目标 for the human人的immune免疫response响应.该提案的具体目标是：1）分离和表征 参与M.卡他皮利。 2)评价M的功能。卡他皮利的定植和发病机制，并表征抗体 对PilA和PilQ的响应。