Surface Proteins of Moraxella catarrhalis

描述（由申请方提供）：卡他莫拉菌被认为是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加重。关于允许M.卡他菌定植于鼻咽粘膜，然后引起呼吸道疾病。这种微生物在鼻咽粘膜表面定殖的能力对其在其他解剖区域引起疾病的能力至关重要，因为这种定殖事件为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），它们在这种细菌的表面上形成突起，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，以确定对生物膜发育至关重要的UspA 1和Hag蛋白的特定区域。在第二个具体目标中，我们将确定那些M。当该生物体附着于人细胞或当该生物体在体内生长时被诱导或上调的卡他表面蛋白。在第三个具体目标中，我们将使用突变分析和毛丝鼠模型的鼻咽定殖M。卡他，以确定这些表面暴露的蛋白质，这种生物体是必不可少的鼻咽定植。最后，在第四个具体目标中，我们将使用这种栗鼠模型来确定这些表面蛋白中的哪一种可以诱导抑制或预防M.粘膜炎。本研究所获得的信息将直接有助于开发有效的疫苗来预防由M.粘膜炎。公共卫生相关性：卡他莫拉氏菌是一种细菌病原体，是婴儿耳部感染和具有某些预先存在的问题（即，慢性阻塞性肺病）。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一种疫苗，以防止M。卡他病

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.