Iron transport and its role in pathogenesis of Vibrio cholerae

铁转运及其在霍乱弧菌发病机制中的作用

• 批准号: 7834648
• 负责人: Shelley M. Payne
• 金额: $ 37.1万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7834648
• 关键词: Anaerobiosis; Bacteria; Be++ element; Beryllium; Binding; Biochemical; Bioinformatics; Cholera; Complement; Complex; Computer Simulation; Elements; Environment; Epidemic; Gene Expression; Genes; Genetic; Goals; Grant; Growth; Heme; Human; Infection; Intestines; Iron; Knowledge; Lead; Mediating; Methods; Molecular; Molecular Biology; Nature; Organism; Pathogenesis; Pattern; Physiology; Play; Post-Transcriptional Regulation; Regulation; Role; Siderophores; Signal Transduction; Small RNA; Source; Starvation; System; Techniques; Temperature; Toxic effect; Vibrio cholerae; Virulence; base; interest; iron metabolism; mutant; novel; pathogen; pathogenic bacteria; perferryl iron; receptor; response; transcription factor; uptake; vibriobactin

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.

霍乱弧菌是引起地方性和流行性霍乱的主要人类病原体， 对铁有绝对的需求。因为霍乱弧菌必须能够在各种环境中获得铁， 在宿主生物体内外的不同环境中，它进化出了多种铁的获取方式 系统，并可以使用来自各种来源的铁。这些铁运输系统包括 内源性铁载体弧菌素、外源性铁载体和血红素的受体以及三价铁 和亚铁吸收系统。铁的运输系统受到严格的管制，以避免铁 饥饿或铁毒性，并且存在铁的转录和转录后调节 运输和铁代谢。调节由铁和全球调节剂Fur以及 小RNA RyhB。有证据表明，需要加强监管。我们将描述V。 胆固醇铁转运系统，其表达的调节，以及它们在V. 环境和宿主中的霍乱。这些系统将使用分子 生物学、遗传学和生物化学技术。当我们完成对所有铁的表征时 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， 剖析环境信号调节表达V的复杂调节网络。 胆固醇铁转运基因该补助金的具体目标是：1）确定完整的补充 胆固醇铁转运系统的研究。2)表征亚铁转运体FeO和新颖的 VciB铁采集系统。这些系统特别令人感兴趣，因为它们都由 细菌在宿主感染过程中，可能是微好氧微生物中的主要铁吸收系统。 肠道的环境。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。这些系统对多种不同的信号做出响应， 优化铁的获取和霍乱弧菌在发现它的各种环境中的生长， 我们建议界定这些规管网络。 了解细菌铁转运系统及其调节是很重要的，因为 病原体与其宿主竞争这种基本元素的能力是病原体的关键组成部分。 寄主-病原体相互作用定义和表征的V. cholesterol铁运输系统在 分子水平，并了解它们在不同环境条件下的表达 将为制定控制这一主要人类病原体的战略提供基础。的结果 这些研究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。