Surface Proteins of Moraxella catarrhalis

卡他莫拉菌的表面蛋白

基本信息

批准号：
8197436
负责人：
Eric John Hansen
金额：
$ 34.62万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
1996
资助国家：
美国
起止时间：
1996-07-01 至 2013-11-30
项目状态：
已结题

项目摘要

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

项目摘要/摘要莫拉氏菌Catarrhalis被认为是婴儿和非常年轻的中耳炎的重要原因儿童，还可能导致成人慢性阻塞性肺部疾病的恶化。几乎没有知道允许卡塔哈里斯菌的基因产物定居于鼻咽粘膜，然后在呼吸道中引起疾病。这种生物体定居的能力鼻咽对在其他解剖区域引起疾病的能力至关重要，因为这殖民事件在其人类宿主中为卡塔哈里斯菌提供了立足点。已经表明M。卡塔哈里斯在体内形成生物膜。现在，我们已经确定了两种不同的表面蛋白（USPA1和HAG）这种形成了该细菌表面的投影，并参与生物膜发育。在第一个具体目的，我们将执行结构功能分析，以确定USPA1的特定区域和对生物膜开发至关重要的伙伴蛋白质。在第二个特定目标中，我们将确定当这种生物附着在人类细胞或这种生物在体内生长时。在第三个特定目的中，我们将使用突变分析以及Cartarhalis M. catarrhalis的鼻咽定植的龙骨模型，以确定哪个这些生物体的表面暴露蛋白对于鼻咽定植至关重要。最后，在第四个特定目的，我们将使用此龙猫模型来确定这些表面蛋白的哪些可以诱导抗体的合成，这些抗体抑制或预防卡塔哈里菌的鼻咽定植。从这项研究中获得的信息将直接受益于开发有效疫苗以防止的努力卡塔尔氏菌引起的呼吸道疾病