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）：卡他莫拉氏菌（Branhamella）现在是 公认是婴儿和青少年中耳炎的重要原因 儿童也可能导致成人下呼吸道感染 慢性阻塞性肺疾病。人们对基因产物知之甚少 使卡他莫拉氏菌定植于鼻咽部，然后在鼻咽部引起疾病 呼吸道。然而，附着在人体细胞上并 抵抗正常人血清的杀伤（即血清抵抗）是 众所周知的细菌毒力因子。我们已经确定了两种不同的 暴露在该病原体表面的蛋白质（UspA1 和 UspA2） 执行与卡他莫拉氏菌能力相关的独特功能 在体内定殖并生存。我们已经确定 UspA1 是 在体外结合人上皮细胞的粘附素。我们还证明了 UspA2 通过此直接参与血清抵抗的表达 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 讨论与感染过程相关的另外两个主题 涉及卡他莫拉菌。在第一个具体目标中，我们将确定氨基 UspA1 蛋白中允许其结合人类上皮细胞的酸序列 细胞。在第二个具体目标中，我们将确定以下机制： UspA2 赋予卡他莫拉氏菌血清抗性和氨基酸序列 UspA2 负责此项活动。旨在确定的实验 血清抵抗所需的 UspA2 水平以及 UspA2 表达情况 监管构成了第三个具体目标。最后，我们将调查 卡他莫拉氏菌生物膜的形成并鉴定参与此过程的基因产物 第四个具体目标中的生物学相关过程。