Surface Proteins of Moraxella catarrhalis

描述(申请人提供)：莫拉氏菌(Branhamella)卡他症 被认为是婴幼儿中耳炎的重要原因 儿童，也可引起成人下呼吸道感染 慢性阻塞性肺病。人们对这些基因产物知之甚少。 使卡他毛虫在鼻咽部定植，然后在 呼吸道。然而，附着在人类细胞上并能够 抵抗正常人血清的杀伤(即血清抵抗)是 公认的细菌毒力因素。我们已经确认了两个不同的 暴露在这种病原体表面的蛋白质(UspA1和UspA2)和 执行与卡他毛虫的能力相关的不同功能 在体内定居并存活。我们已经确定UspA1是一个 在体外结合人类上皮细胞的粘附素。我们也证明了 UspA2通过这种方式直接参与血清耐药的表达 有机体。这项研究项目涉及到对 这两种蛋白质固有的结构-功能关系，以及 讨论与传染过程相关的另外两个主题 涉及卡特哈里分枝杆菌。在第一个具体目标中，我们将识别氨基 UspA1蛋白中的酸性序列(S)，使其能够与人上皮细胞结合 细胞。在第二个具体目标中，我们将确定 UspA2对卡他支原体及其氨基酸序列的血清抗性(S) 在UspA2中负责这一活动。实验旨在确定 血清抵抗所需的UspA2水平以及UspA2的表达 监管构成了第三个具体目标。最后，我们将调查 卡他莫拉菌生物膜的形成及其相关基因产物的鉴定 第四个具体目标中的生物相关过程。

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.