Surface Proteins of Moraxella catarrhalis

描述（由申请人提供）：卡他莫拉菌（布兰汉菌）目前 被认为是婴儿和年轻人中耳炎的重要原因 儿童，也可能导致成人下呼吸道感染， 慢性阻塞性肺疾病对基因产物知之甚少 这使得M。卡他菌在鼻咽部定植， 呼吸道然而，附着在人体细胞上的能力， 抵抗正常人血清的杀伤（即，血清抵抗） 公认的细菌毒力因子。我们发现了两个不同的 暴露于该病原体表面的蛋白质（UspA 1和UspA 2）， 执行与M的能力相关的不同功能。卡他 定殖并在体内存活。我们已经确定UspA 1是一种 在体外结合人类上皮细胞的粘附素。我们也证明了 UspA 2直接参与血清抵抗的表达， 有机体该研究项目涉及调查 这两种蛋白质固有的结构-功能关系， 讨论了与感染过程相关的另外两个主题 涉及M.粘膜炎。在第一个具体目标中，我们将确定氨基 UspA 1蛋白中允许其结合人上皮细胞的酸性序列 细胞在第二个具体目标中，我们将确定 UspA 2赋予M.和氨基酸序列 在UspA 2中负责此活动。实验旨在确定 血清抗性所需的UspA 2水平以及UspA 2表达如何影响 第三个具体目标是规范。最后，我们将调查 M.卡他并鉴定与此有关的基因产物 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.