Heme as an iron source in Sinorhizobium meliloti

描述(申请人提供)：除了它的许多细胞功能，血红素也是许多细菌的营养铁的来源。在动物的细菌病原体中，血红素的获取和代谢是致病的关键，但这一系统仅在相对较少的属中被定义。最近的研究表明，苜蓿中华根瘤菌及其近缘种利用血红素作为营养铁源。苜蓿链霉菌所属的蛋白细菌群包括在致病或共生环境中与高等真核生物形成胞内或密切联系的细菌。初步证据表明，在共生的苜蓿链霉菌中，参与血红素运输和代谢的基因在相关动物病原体中具有同源性。这项拟议工作的广泛目标是将紫花苜蓿中的血红素利用系统表征为一个实验上易于处理的-蛋白细菌模型，并确定致病和与高等真核生物共生相互作用的共同分子主题。ShmR蛋白是一种可能的血红素受体，被鉴定为与血红素结合的外膜蛋白，并以铁依赖的方式表达。证据表明，shmR在转录水平上受一种迄今未知的调控系统的控制。ShmR同源物在分类相关的病原体中被发现。提出了两个具体目标来解决依赖铁控制血红素运输的问题。1)确定shmR启动子中介导铁调控的顺式作用元件。2)鉴定介导shmR基因铁调控的调控蛋白。铁对shmR的控制不是由两个已知的监管机构IRR或Fur来调节的。对shmR启动子中铁反应顺式作用元件的鉴定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克莱门特研究所与埃琳娜·法比亚诺合作进行，作为NIH赠款的延伸R01GM067966。根据世界银行的分类系统，乌拉圭的人均国民总收入为3790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 ?-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.