Heme as an iron source in Sinorhizobium meliloti

血红素作为苜蓿中华根瘤菌的铁源

• 批准号: 7436312
• 负责人: MARK R O'BRIAN
• 金额: $ 3.82万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-15 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7436312
• 关键词: Address; Affect; Anabolism; Animals; Bacteria; Binding; Biochemical Genetics; Cell physiology; Cells; Classification; Collaborations; Condition; DNA; DNA Binding; Dissociation; Elements; Environment; Enzymes; Eukaryota; Eukaryotic Cell; Gene Expression; Gene Targeting; Genes; Genetic; Grant; Heme; Heme Iron; Homeostasis; Homologous Gene; Income; Indium; Iron; Localized; Mediating; Melilotus; Membrane Proteins; Metabolic Control; Metabolism; Modeling; Molecular; Normal Cell; Nutrient; Nutritional; Organism; Pathway interactions; Porphyrins; Property; Protein Binding; Proteins; Proteobacteria; Proteolysis; Protoporphyrins; Reaction; Regulation; Regulon; Repression; Research; Rhizobium; Role; Signaling Molecule; Sinorhizobium meliloti; Site; Source; System; Toxic effect; United States National Institutes of Health; Uruguay; Virulence; Work; World Bank; base; cis acting element; cytotoxic; ferrochelatase; genetic regulatory protein; heme a; heme biosynthesis; heme receptor; iron metabolism; novel; oxidation; parent grant; pathogen; prevent; promoter; research study; response; success; tool

DESCRIPTION (provided by applicant): In addition to its many cellular functions, heme is also a source of nutritional iron for many bacteria. The acquisition and metabolism of heme is essential for virulence in bacterial pathogens of animals, but this system has only been defined in relatively few genera. It was shown recently that S. meliloti uses heme as a nutritional iron source in Sinorhizobium meliloti and related species. The ?-proteobacterial group to which S. meliloti belongs includes bacteria that form intracellular or close associations with higher eukaryotes in either a pathogenic or symbiotic context. Preliminary evidence suggests that genes involved in heme transport and metabolism in symbiotic S. meliloti have homologs in related animal pathogens. The broad objective of the proposed work is to characterize the heme utilization system in S. meliloti as an experimentally tractable model for the ?-proteobacteria, and to identify common molecular themes in pathogenic and symbiotic interactions with higher eukaryotes. The ShmR protein is a putative heme receptor that was identified as an outer membrane protein that binds heme, and is expressed in an iron-dependent manner. Evidence indicates that shmR is transcriptionally controlled by a heretofore unidentified regulatory system. ShmR homologs are found in taxonomically-related pathogens. Two specific aims are proposed to address iron-dependent control of heme transport. 1) Identify the cis-acting element within the shmR promoter that mediates control by iron. 2) Identify the regulatory protein that mediates iron control of the shmR gene. Control of shmR by iron is not mediated by the two known regulators, Irr or Fur. Identification of the iron-responsive cis-acting element within the shmR promoter gives us the means to identify the cognate regulator protein. This research will be done primarily in Montevideo, Uruguay at the Instituto de Investigaciones Bioldgicas Clemente Estable in collaboration with Elena Fabiano as an extension of NIH grant R01GM067966. The gross national income per capita of Uruguay is $3,790 according to the World Bank classification system.

描述（由申请人提供）：除了其许多细胞功能外，血红素也是许多细菌的营养铁的来源。血红素的获得和代谢对于动物细菌病原体的毒力至关重要，但是该系统仅在相对较少的属中被定义。最近显示，梅洛蒂（S. Meliloti）在梅洛蒂（Sinorhizobium Meliloti）和相关物种中使用血红素作为营养铁源。在致病性或共生环境中，梅洛蒂（S. meliloti）所属的蛋白细菌群包括与较高的真核生物形成细胞内或密切关联的细菌。初步证据表明，在相关的动物病原体中，梅尔洛蒂菌中涉及血红素转运和代谢的基因具有同源性。拟议工作的广泛目标是将梅洛蒂（S. meliloti）中的血红素利用系统表征为？ - 蛋白杆菌的实验可行模型，并鉴定与高级真核生物的致病性和共生相互作用中常见的分子主题。 SHMR蛋白是一种假定的血红素受体，被鉴定为结合血红素的外膜蛋白，并以铁依赖性方式表达。证据表明，SHMR是由迄今未识别的监管系统在转录控制的。 SHMR同源物在与分类学相关的病原体中发现。提出了两个具体的目的，以解决血红素转运的铁依赖性控制。 1）确定SHMR启动子中介导铁控制的顺式作用元件。 2）确定介导铁控制SHMR基因的调节蛋白。铁对SHMR的控制不是由两个已知调节剂（IRR或毛皮）介导的。 SHMR启动子中铁响应性顺式作用元件的鉴定使我们能够识别识别同源调节蛋白。这项研究将主要在Respocitimenes Bioldgicas Clemente clemente Instituto与Elena Fabiano一起与Elena Fabiano合作进行，作为NIH Grant R01GM067966的扩展。根据世界银行分类系统，乌拉圭人均国民总收入总收入为3,790美元。