Heme as an iron source in Sinorhizobium meliloti

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来源。血红素的获得和代谢对于动物病原菌的毒力是必不可少的，但这一系统仅在相对较少的属中被定义。最近的研究表明，S.苜蓿中华根瘤菌和相关物种使用血红素作为营养铁源。S.苜蓿属包括在致病或共生环境中与高等真核生物形成细胞内或紧密结合的细菌。初步证据表明，在共生S。苜蓿草在相关动物病原体中具有同源物。这项工作的主要目标是研究S.苜蓿草作为实验上易于处理的模型的α-变形菌，并确定共同的分子主题与高等真核生物的致病性和共生相互作用。ShmR蛋白是推定的血红素受体，其被鉴定为结合血红素的外膜蛋白，并且以铁依赖性方式表达。有证据表明，shmR是由一个迄今尚未确定的调控系统转录控制。ShmR同源物存在于分类学相关的病原体中。提出了两个具体的目标，以解决铁依赖控制血红素运输。1)鉴定shmR启动子内介导铁控制的顺式作用元件。2)鉴定介导铁对shmR基因控制的调节蛋白。铁对shmR的控制不受两种已知调节剂Irr或Fur介导。鉴定shmR启动子内的铁响应性顺式作用元件为我们提供了鉴定同源调节蛋白的手段。这项研究将主要在乌拉圭蒙得维的亚的Instituto de Investigaciones Bioldgicas Clemente Estable与Elena Fabiano合作完成，作为NIH资助R 01 GM 067966的延伸。根据世界银行分类系统，乌拉圭人均国民总收入为3 790美元。

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 alpha-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 alpha-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.