IRON ASSIMILATION BY PATHOGENIC NEISSERIA SPP

淋病奈瑟菌和脑膜炎奈瑟菌定植的部位 在人类宿主中是多样的，每个位点都代表着一个独特的生态位。 营养、环境因素和竞争 微生物的 生长环境对植物生长发育有显著影响。 代谢和细胞组成。淋病奈瑟菌和淋病奈瑟菌。脑膜炎， 细胞组成的改变通常反映在 这些微生物与人类宿主的关系。 本项目的总体目标是阐明特定的机制 被致病性奈瑟氏菌用于吸收必需的 营养铁。 我们将把大部分精力集中在主要的铁- 调节蛋白，Fep。 最近克隆的fep可以让我们创造 通过miniT13诱变产生Fep缺陷的突变体。 我们将 检查fep结构基因5 '端的DNA序列， 铁调节Fep的表达。 我们还将研究 铁的铁。 将确定淋球菌Fep在细胞中的具体位置 通过渗透压休克技术，以及它与其他细胞的相互作用， 组件通过交联技术。 最后，我们将利用我们最近 描述了N.脑膜炎球菌Tn916诱变系统分离特异性 铁利用缺陷的突变体。 由此产生的变异DNA 用作探针以克隆相应的野生型DNA。 这些研究中产生的突变体将在我们的动物体内进行检查 模型 将采用小鼠皮下室模型进行研究 对N.淋病奈瑟菌和淋病奈瑟菌。脑膜炎突变体 此外，本发明还提供了一种方法， 我们将检查N。在小鼠菌血症模型中的脑膜炎突变体。 这些研究将使我们能够评估铁的利用在 生长和随后的致病性。淋病 和n.脑膜炎

The sites colonized by Neisseria gonorrhoeae and Neisseria meningitidis within the human host are diverse and each site represents a unique niche with respect to nutrients, environmental factors and competing microorganisms. The growth environment has a marked effect on the metabolism and cellular composition of N. gonorrhoeae and N. meningitidis, and an altered cellular composition is often reflected in the interaction of these microorganisms with the human host. The overall goal of this project is to elucidate the specific mechanisms employed by the pathogenic Neisseria for the assimilation of the essential nutrient iron. We will focus a majority of our efforts on the major iron- regulated protein, Fep. The recently cloned fep will allow us to create mutants defective in the production of Fep by miniT13 mutagenesis. We will examine the DNA sequences 5' to the fep structural gene and investigate how iron regulates the expression of Fep. We will also examine the regulation by iron of the Fep transcript. The specific location of the gonococcal Fep in the cell will be determined by osmotic shock techniques, as well as its interaction with other cellular components by cross-linking techniques. Finally, we will use our recently described N. meningitidis Tn916 mutagenesis system to isolate specific mutants defective in iron utilization. The resulting mutated DNA will be used as probes to clone the corresponding wildtype DNA. Mutants generated in these studies will be examined in vivo in our animal models. The mouse subcutaneous chamber model will be employed for studies on the growth of N. gonorrhoeae and N. meningitidis mutants. In addition, we will examine N. meningitidis mutants in the mouse bacteremia model. These studies will allow us to evaluate the role of iron utilization in the growth and subsequent pathogenicity of infection caused by N. gonorrhoeae and N. meningitidis.