ENTACTIN BINDING PROTEINS OF CANDIDA ALBICANS

简介(摘自申请者摘要)：白色念珠菌等 机会性病原体已经变得越来越重要，因为 科学改进了其他疾病的治疗方法。这种二相性真菌是 一种可能危及生命的疾病的媒介。这个有机体是人类 共病和感染一般是内源性的。这项建议是 旨在研究播散性疾病发病机制中的一个早期事件 疾病：与宿主组织粘连。真菌粘附素是一种推定的毒力 各种因素。黏附是开发抗真菌药物的潜在靶点 治疗，以补充目前有限的选择。坚持 细胞外基质(ECM)与播散性念珠菌有关 感染。该提案重点关注在酵母细胞中发现的三种蛋白质和 与细胞外基质成分entactin结合的生殖管。功能和 这些蛋白质的结构关系将被阐明。生化的， 免疫学和分子技术将被用来确定 受体的配体特异性、定位和表达之间的关系 结合蛋白。一种将粘附性与其他粘附性分开的体外试验 发病机制参数将用于阐明组织特异性。 以及entactin介导的黏附特性。小鼠的脾、肺、 肾脏、肝脏组织和灵长类组织将被检查。这些组织 是播散性念珠菌病的主要目标。突变株在 肌动蛋白结合蛋白(S)的表达将用 适当的基因破坏和缺陷亚单位方法。标准 将使用技术来克隆和测序牙本质蛋白的基因(S) 结合蛋白。克隆的序列(S)将用于突变 建筑。缺陷菌株将被鉴定为entactin。 捆绑和组织粘连。这些粘附剂的相互作用在 发病机制将在体内的小鼠粘连模型中进行评估。

DESCRIPTION (Adapted from applicant's abstract): Candida albicans and other opportunistic pathogens have become increasingly important as medical science improves the treatments of other diseases. This dimorphic fungus is an agent of potentially life threatening disease. The organism is a human comensal and infection is generally of endogenous origin. This proposal is directed towards studying an early event in the pathogenesis of disseminated disease: adhesion to host tissues. Fungal adhesins are putative virulence factors. Adherence is a potential target for development of anti-fungal therapy to supplement the limited options currently available. Adherence to the extracellular matrix (ECM) has been implicated in disseminated Candida infection. The proposal focuses on three proteins found in yeast cells and germ tubes that bind to the ECM component entactin. The functional and structural relationships of these proteins will be elucidated. Biochemical, immunological, and molecular techniques will be used to determine the relationship between ligand specificity, localization, and expression of the binding proteins. An ex vivo assay that separates adherence from other parameters of pathogenesis will be used to elucidate the tissue specificity and characteristics of entactin mediated adherence. Murine spleen, lung, kidney, and liver tissue and primate tissue will be examined. These tissues are major targets of disseminated candidiasis. Mutant strains altered in the expression of entactin binding proteins(s) will be constructed using gene disruption and defective subunit approaches as appropriate. Standard techniques will be used to clone and sequence the gene(s) for entactin binding proteins. The cloned sequence(s) will be used in mutant construction. The deficient strains will be characterized for entactin binding and tissue adherence. The role of these adhesive interactions in pathogenesis will be evaluated in an in vivo murine model of adherence.