FHA-LIKE PROTEIN OF HAEMOPHILUS DUCREYI

下巴是一种由禁食引起的性传播疾病 杜氏嗜血杆菌。我已经辨认出一段杜克雷人的 编码一种与丝状菌有43%相似性的蛋白质的基因组DNA 百日咳杆菌血凝素(FHA)；可检测到该蛋白 在杜氏嗜血杆菌培养上清液中。我提议结合使用 分子遗传学、免疫电子显微镜、黏附研究以及 活体毒力试验研究这一类杜氏杆菌FHA的作用 蛋白质在软骨病发病机制中的作用。1)这方面的主要目标 该项目是识别、克隆和测序完整的编码基因 杜氏嗜血杆菌FHA样蛋白，并确定杜氏嗜血杆菌 含有第二个编码FHA样蛋白的基因。2)蜂窝 这种推定的粘附素的位置将被确定，并可能 将研究如何将前体加工成成熟的形式。3) 缺乏FHA样蛋白生产的杜氏嗜血杆菌等基因突变株 将构建蛋白质(S)并测试其结合能力 几种不同的人类细胞系和细胞外基质 组件。4)这些突变体也将在两个方面进行评估 温敏性兔和实验性人软下巴模型 确定FHA样蛋白在毒力中的作用 由H.Dureyi表达。

Chancroid is a sexually transmitted disease caused by the fastodious bacterium Haemophilus ducreyi. I have identified a segment of H. ducreyi genomic DNA encoding a protein with 43% similarity to the filamentous hemagglutinin (FHA) of Bordetella pertussis; this protein can be detected in H. ducreyi cultre supernatants. I proposed to use a combination of molecular gentics, immunoelectron microscopy, adherence studies, and in vivo virulenc teting to investigate the role of this H. ducreyi FHA-like protein in the pathogenesis of chancroid. 1) A primary goal of this project is to identify, clone, and sequence the complete gene encoding the H. ducreyik FHA-like protein and to determine whether H. ducreyi contains a second gene encoding and FHA-like protein. 2) The cellular location of this putative adhesin will be determine adn the potential for processing of a precursor into a mature form will be investigated. 3) Isogenic H. ducreyi mutants deficient in the production of the FHA-like proteins (s) will be constructed and tested for their abilities to bind to several different human cell lines and extracellular matrix components. 4) These mutants wil also be evaluated in both the temperature-dependent rabbit and experimental human models of chancroid to determine the involvment of the FHA-like protein in virulence expression by H. ducreyi.