Surface Proteins of Moraxella catarrhalis

卡他莫拉氏菌的表面蛋白

• 批准号: 7993086
• 负责人: Eric John Hansen
• 金额: $ 34.62万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-07-01 至 2013-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7993086
• 关键词: Adult; Affect; Anatomy; Animal Model; Antibodies; Antigens; Bacteria; Cells; Child; Chinchilla (genus); Chronic Obstructive Airway Disease; DNA Microarray Chip; Development; Disease; Event; Gram-Negative Bacteria; Growth; Health; Human; In Vitro; Individual; Infant; Lower respiratory tract structure; Membrane Proteins; Methods; Microarray Analysis; Microbial Biofilms; Modeling; Moraxella (Branhamella) catarrhalis; Mucous Membrane; Nasopharynx; Organism; Otitis Media; Protein Region; Proteins; Research; Respiratory System; Respiratory Tract Diseases; Respiratory tract structure; Structure; Surface; Technology; Vaccines; ear infection; in vivo; mutant; pathogen; prevent

DESCRIPTION (provided by applicant): Moraxella catarrhalis is acknowledged as an important cause of otitis media in infants and very young children and can also cause exacerbations of chronic obstructive pulmonary disease in adults. Little is known about the gene products that allow M. catarrhalis to colonize the nasopharyngeal mucosa and then cause disease in the respiratory tract. The ability of this organism to colonize the mucosal surface of the nasopharynx is crucial to its ability to cause disease in other anatomic regions because this colonization event provides a foothold for M. catarrhalis in its human host. It has been shown that M. catarrhalis forms a biofilm in vivo. We have now identified two different surface proteins (UspA1 and Hag) that form projections on the surface of this bacterium and which are involved in biofilm development. In the first Specific Aim, we will perform structure-function analysis to identify the specific regions of the UspA1 and Hag proteins that are essential for biofilm development. In the second Specific Aim, we will identify those M. catarrhalis surface proteins that are induced or up-regulated when this organism attaches to human cells or when this organism grows in vivo. In the third Specific Aim, we will use mutant analysis together with a chinchilla model of nasopharyngeal colonization by M. catarrhalis to determine which of these surface-exposed proteins of this organism are essential for nasopharyngeal colonization. Finally, in the fourth Specific Aim, we will use this chinchilla model to determine which of these surface proteins can induce the synthesis of antibodies which inhibit or prevent nasopharyngeal colonization by M. catarrhalis. Information gained from this study will directly benefit efforts to develop an effective vaccine to prevent respiratory tract disease caused by M. catarrhalis. PUBLIC HEALTH RELEVANCE: Moraxella catarrhalis is a bacterial pathogen that is an important cause of ear infections in babies and serious respiratory tract disease in adults with certain preexisting problems (i.e., chronic obstructive pulmonary disease). Information obtained from this research will identify components of this bacterium that have the potential to be developed into a vaccine to protect against M. catarrhalis disease.

描述（由申请人提供）：卡他氏菌被认为是婴儿和非常年幼的儿童中耳炎的重要原因，还可能导致成人慢性阻塞性肺部疾病的加剧。关于允许卡塔哈里斯氏菌的基因产物知之甚少，然后在呼吸道中引起鼻咽粘膜，然后引起疾病。这种生物体定居鼻咽粘膜表面的能力对于在其他解剖区域引起疾病的能力至关重要，因为这种定殖事件为卡塔哈里斯菌在其人类宿主中提供了立足点。已经表明，卡塔尔氏菌在体内形成生物膜。现在，我们已经确定了两种不同的表面蛋白（USPA1和HAG），它们在该细菌表面形成投影，并参与生物膜发育。在第一个特定目的中，我们将执行结构功能分析，以确定对生物膜开发至关重要的USPA1和HAG蛋白的特定区域。在第二个特定目的中，我们将确定当该生物附着在人类细胞上或这种生物在体内生长时，会诱导或上调的那些卡塔哈利菌表面蛋白。在第三个特定目的中，我们将使用突变分析以及卡塔尔哈利菌的鼻咽定植的龙骨模型来确定这种生物体的这些表面暴露的蛋白质中的哪种对于鼻咽定植至关重要。最后，在第四个特定目的中，我们将使用该龙猫模型来确定这些表面蛋白中的哪些可以诱导抗体的合成，这些抗体抑制或预防卡塔尔哈利菌的鼻咽定植。从这项研究中获得的信息将直接受益于开发有效的疫苗，以防止卡塔哈里斯菌引起的呼吸道疾病。公共卫生相关性：摩纳半菌Catarrhalis是一种细菌病原体，是婴儿耳部感染的重要原因，在患有某些先前存在的问题（即慢性阻塞性肺部疾病）的成年人中，患有婴儿的耳朵感染和严重的呼吸道疾病。从这项研究中获得的信息将确定该细菌的成分，这些细菌有可能发展为疫苗以防止卡他氏菌疾病。