Surface Proteins of Moraxella catarrhalis

项目总结/摘要 卡他莫拉菌是公认的一个重要原因中耳炎的婴儿和非常年轻 也可能导致成人慢性阻塞性肺疾病的恶化。之甚少 已知的基因产物，使M。卡他菌定植于鼻咽粘膜， 引起呼吸道疾病。这种微生物能够定植在粘膜表面， 鼻咽对于它在其它解剖区域引起疾病的能力是至关重要的 定殖事件为M.在人类宿主体内引起卡他病。结果表明，M. 卡他在体内形成生物膜。我们现在已经确定了两种不同的表面蛋白（UspA 1和Hag） 在细菌表面形成突起，并参与生物膜的形成。在 第一个特异性目的，我们将进行结构-功能分析，以确定UspA 1的特定区域 和对生物膜发育必不可少的Hag蛋白。在第二个具体目标中，我们将确定 这些M。卡他表面蛋白，当这种生物附着在 人类细胞或当这种生物体在体内生长时。在第三个特定目标中，我们将使用突变分析 以及M.卡他炎，以确定 该生物体的这些表面暴露的蛋白质对于鼻咽定殖是必需的。最后在 在第四个特定目标中，我们将使用这个栗鼠模型来确定这些表面蛋白中的哪一个可以 诱导抑制或预防M.粘膜炎。 从这项研究中获得的信息将直接有助于开发有效的疫苗来预防 呼吸道疾病由M. catarrhalis

Project Summary/Abstract 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