Surface Proteins of Moraxella catarrhalis

描述(申请人提供)：卡他莫拉氏菌被公认为婴儿和幼儿中耳炎的重要原因，也可导致成人慢性阻塞性肺疾病的恶化。卡氏支原体可以在鼻咽粘膜上定植，然后在呼吸道引起疾病的基因产物知之甚少。这种细菌在鼻咽粘膜表面的定植能力对它在其他解剖区域引起疾病的能力至关重要，因为这种定植事件为卡他毛虫在其人类宿主中提供了立足点。研究表明，卡氏支原体在体内形成生物膜。我们现在已经鉴定了两种不同的表面蛋白(UspA1和HAG)，它们在这种细菌的表面形成投影，并参与生物膜的发育。在第一个特定目标中，我们将进行结构功能分析，以确定UspA1和HAG蛋白的特定区域，这些区域对生物膜的发育是必不可少的。在第二个特定目标中，我们将鉴定当卡氏支原体附着在人类细胞上或在体内生长时诱导或上调的卡氏支原体表面蛋白。在第三个特定目标中，我们将使用突变分析和卡他分支杆菌鼻咽定植的栗鼠模型来确定这种生物的这些表面暴露的蛋白质中的哪些是鼻咽定植所必需的。最后，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些可以诱导合成抗体来抑制或防止卡他毛虫在鼻咽的定植。从这项研究中获得的信息将直接有助于努力开发有效的疫苗来预防卡他分枝杆菌引起的呼吸道疾病。与公共卫生相关：卡他莫拉氏菌是一种细菌病原体，是婴儿耳部感染和成人严重呼吸道疾病(即慢性阻塞性肺疾病)的重要原因。从这项研究中获得的信息将确定这种细菌的成分，这些成分有可能被开发成预防卡特哈里分枝杆菌病的疫苗。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: Moraxella catarrhalis is a bacterial pathogen that is an important cause of ear infections in babies and serious respiratory tract disease in adults with certain preexisting problems (i.e., chronic obstructive pulmonary disease). Information obtained from this research will identify components of this bacterium that have the potential to be developed into a vaccine to protect against M. catarrhalis disease.