V. cholerae iron transport mechanisms and pathogenesis

描述(申请人提供)：大多数细菌病原体对铁有绝对的要求。大多数环境中铁的低可获得性导致 与高亲和力铁运输系统的进化有关。虽然铁 已经在几种革兰氏阴性生物中发现了获取系统， 使用的铁的来源和不同系统的相对贡献 在寄主中的生长和生存以及在不同的生态位中 对外部环境不了解。霍乱弧菌，病原体 霍乱是世界范围内发病率和死亡率相当高的疾病。 这种有机体容易受到基因操纵，以及几种铁的获取 系统已经被识别出来。然而，遗传分析表明， 霍乱弧菌中还有额外的高亲和力铁转运系统。这个 最近完成的它的基因组序列将使我们能够识别 其余的铁获取系统和严格审查的作用 不同环境中的系统以及暴露在不同环境中的系统 环境压力。 我们的第一个具体目标是完成我们对霍乱弧菌血红素的表征 运输和利用。我们的基因数据表明，这种病原体 表达多种血红素运输系统，我们将定义哪些基因是 是运输血红素所必需的。我们还将继续对基因进行表征 这一功能在血红素被运输到 手机。我们的第二个具体目标是确定用于 霍乱弧菌利用的两种外源铁载体：肠杆菌素和肠杆菌素 五味子碱。第三个具体目标是一起使用我们的突变体集合 使用其他试剂，以确定在 特定的环境条件，以及在脊椎动物宿主的生长过程中。

DESCRIPTION (provided by applicant): Most bacterial pathogens have an absolute requirement for iron. The low availability of iron in most environments has led to the evolution of high affinity iron transport systems. Although iron acquisition systems have been identified in several gram negative organisms, the sources of iron used and the relative contribution of the different systems in their growth and survival in the host and in different niches in the external environment are not understood. Vibrio cholerae, the causative agent of cholera, is responsible for considerable morbidity and mortality worldwide. This organism is amenable to genetic manipulation, and several iron acquisition systems have already been identified. However, genetic analysis indicates that there are additional high-affinity iron transport systems in V. cholerae. The recent completion of its genome sequence will allow us to identify the remaining iron acquisition systems and to rigorously examine the roles of the systems in different environments and during exposure to different environmental stresses. Our first Specific Aim is to complete our characterization of V. cholerae heme transport and utilization. Our genetic data indicate that this pathogen expresses multiple heme transport systems, and we will define which genes are required for heme transport. We will also continue characterization of genes that function in the utilization of heme after it has been transported into the cell. Our second Specific Aim is to identify the transport systems used for the uptake of two exogenous siderophores used by V. cholerae, enterobactin and schizokinen. The third Specific Aim is to use our mutant collection, together with other reagents, to determine which transport systems are used during specific environmental conditions, and during growth in the vertebrate host.