Iron transport and its role in pathogenesis of Vibrio cholerae

霍乱弧菌是导致霍乱流行和流行的主要人类病原体， 对铁有绝对的要求。因为霍乱弧菌必须能够从各种不同的 不同的寄主生物内外环境，它进化出了多种铁的获取 而且可以使用来自各种来源的铁。这些铁质运输系统包括 内源性铁载体弧菌蛋白、外源铁载体受体、血红素受体和铁 和亚铁摄取系统。铁运输系统受到严格监管，以避免铁或铁 饥饿或铁中毒，铁的转录和转录后调节都存在 运输和铁代谢。监管由Iron和全球监管机构Fur和 小RNA RyhB。有证据表明存在额外的监管水平。我们将描述V。 霍乱弧菌铁转运系统、其表达的调控及其在霍乱弧菌生存中的作用。 环境和宿主中的霍乱弧菌。这些系统将用分子表征 生物学、遗传学和生化技术。当我们完成对所有铁元素的表征时 这种病原体使用的运输系统，我们可以确定它们在发病机制中的作用，并进一步 解剖复杂的调控网络，环境信号通过该网络调控表达V。 霍乱弧菌铁转运基因。这笔赠款的具体目的是：1)确定完整的补充物 霍乱弧菌的铁运输系统。2)刻画《铁皮运输车FeO》及其小说 VCIB铁采集系统。这些系统特别令人感兴趣，因为它们都由 细菌在宿主感染期间，很可能是微氧中主要的铁摄取系统 肠道环境。3)确定霍乱弧菌铁转运的调节机制 基因对环境信号的反应。系统对多个不同的信号做出响应 在发现霍乱弧菌的各种环境中优化铁的获取和生长， 我们建议对这些监管网络进行定义。 了解细菌铁运输系统及其调控是很重要的，因为 病原体与宿主竞争这一基本元素的能力是 寄主-病原菌相互作用。霍乱弧菌铁运输系统的定义和特征 分子水平及其在不同环境条件下的表达 将为制定控制这一人类主要病原体的战略提供基础。结果是 这些研究很可能广泛适用于人类致病菌，因为大多数 它们必须在感染期间获得铁。

Vibrio cholerae, a major human pathogen responsible for both endemic and epidemic cholera, has an absolute requirement for iron. Because V. cholerae must be able to obtain iron in a variety of different environments in and outside of host organisms, it has evolved multiple iron acquisition systems and can use iron from a variety of sources. These iron transport systems include the endogenous siderophore vibriobactin, receptors for exogenous siderophores and for heme, and ferric and ferrous iron uptake systems. Iron transport systems are tightly regulated to avoid either iron starvation or iron toxicity, and there is both transcriptional and post-transcriptional regulation of iron transport and iron metabolism. Regulation is mediated by iron and the global regulator Fur and by the small RNA RyhB. There is evidence for additional levels of regulation. We will characterize the V. cholerae iron transport systems, the regulation of their expression, and their role in survival of V. cholerae in the environment and in the host. These systems will be characterized using molecular biology, genetics, and biochemical techniques. As we complete the characterization of all the iron transport systems that this pathogen uses, we can determine their roles in pathogenesis and further dissect the complex regulatory network by which environmental signals regulate the expression V. cholerae iron transport genes. The specific aims of this grant are: 1) Identify the complete complement of V. cholerae iron transport systems. 2) Characterize the ferrous iron transporter Feo and the novel VciB iron acquisition system. These systems are of particular interest since they are both expressed by bacteria during infection of the host and are likely to be major iron uptake systems in the microaerobic environment of the intestine. 3) Determine the mechanism of regulation of V. cholerae iron transport genes in response to environmental signals. The systems respond to multiple, different signals to optimize iron acquisition and growth of V. cholerae in the variety of environments in which it is found, and we propose to define these regulatory networks. It is important to understand bacterial iron transport systems and their regulation, because the ability of pathogens to compete with their host for this essential element is a critical component of the host-pathogen interaction. Defining and characterizing the V. cholerae iron transport systems at the molecular level and understanding their expression in response to different environmental conditions will provide the basis for developing strategies to control this major human pathogen. The results of these studies are likely to be broadly applicable to human pathogenic bacteria, since the majority of them must acquire iron during infection.