Surface Proteins of Moraxella catarrhalis

卡他莫拉菌的表面蛋白

• 批准号: 6881095
• 负责人: Eric John Hansen
• 金额: $ 31.2万
• 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 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6881095
• 关键词: Moraxella; antibacterial antibody; bacteria infection mechanism; bacterial proteins; bactericidal immunity; biofilm; cell adhesion; clinical research; complement; human subject; laboratory mouse; microorganism growth; molecular film; mucosa; protein sequence; protein structure function; recombinant proteins; surface antigens; virulence

DESCRIPTION (provided by applicant): Moraxella (Branhamella) catarrhalis is now acknowledged to be an important cause of otitis media in infants and young children and can also cause lower respiratory tract infections in adults with chronic obstructive pulmonary disease. Little is known about the gene products that allow M. catarrhalis to colonize the nasopharynx and then cause disease in the respiratory tract. However, the ability to attach to human cells and to resist killing by normal human serum (i.e., serum resistance) are well-recognized bacterial virulence factors. We have identified two different proteins (UspA1 and UspA2) that are exposed on the surface of this pathogen and that perform distinct functions relevant to the ability of M. catarrhalis to colonize and survive in vivo. We already have established that UspA1 is an adhesin that binds human epithelial cells in vitro. We also have proven that UspA2 is directly involved in the expression of serum resistance by this organism. This research project involves investigation of the structure-function relationships inherent in these two proteins and also addresses two other topics that are relevant to the infectious process involving M. catarrhalis. In the first Specific Aim, we will identify the amino acid sequence(s) in the UspA1 protein that allows it to bind human epithelial cells. In the second Specific Aim, we will identify both the mechanism by which UspA2 confers serum resistance on M. catarrhalis and the amino acid sequence(s) in UspA2 responsible for this activity. Experiments designed to determine the level of UspA2 required for serum resistance and how UspA2 expression is regulated constitute the third Specific Aim. Finally, we will investigate biofilm formation by M. catarrhalis and identify gene products involved in this biologically relevant process in the fourth Specific Aim.

描述（由申请人提供）：Moraxella（Branhamella）Catarrhalis现在 公认是婴儿和年轻人中耳炎的重要原因 儿童，还可能引起成年人的下呼吸道感染 慢性阻塞性肺疾病。关于基因产品知之甚少 这允许卡塔哈里斯分枝杆菌在鼻咽上定居，然后引起疾病 呼吸道。但是，能够附着在人类细胞上并 抵抗正常人血清杀死（即血清抗性）是 公认的细菌毒力因子。我们已经确定了两个不同的 蛋白质（USPA1和USPA2）暴露在该病原体的表面和 该执行与Cartarrhals M. catarrhalis的能力相关的不同功能 在体内殖民并生存。我们已经确定USPA1是 在体外结合人上皮细胞的粘附素。我们也证明了 USPA2直接参与了血清抗性的表达 生物。该研究项目涉及调查 这两种蛋白质固有的结构功能关系，也 解决与传染过程有关的其他两个主题 涉及Cartarrhalis M.。在第一个特定目标中，我们将确定氨基 USPA1蛋白中的酸序列，允许其结合人类上皮 细胞。在第二个特定目标中，我们将确定 USPA2赋予了卡塔尔氏菌和氨基酸序列的血清耐药性（S） 在USPA2中负责此活动。旨在确定的实验 血清抗性所需的USPA2水平以及USPA2表达方式 受监管构成第三个特定目标。最后，我们将调查 Cartarrhalis M. Cartarrhal的生物膜形成，并鉴定与此有关的基因产物 在第四个特定目标中与生物学相关的过程。