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Iron transport in Shigella and pathogenic E.coli

志贺氏菌和致病性大肠杆菌中的铁转运

基本信息

批准号：
7144990
负责人：
Shelley M. Payne
金额：
$ 27.97万
依托单位：
UNIVERSITY OF TEXAS AT AUSTIN
依托单位国家：
美国
项目类别：
财政年份：
1980
资助国家：
美国
起止时间：
1980-09-30 至 2007-11-30
项目状态：
已结题

项目摘要

Most bacterial pathogens have an absolute requirement for iron. The low availability of iron in most environments has led to the evolution of high affinity iron transport systems. Although a variety of iron transport systems have been identified in Shigella and pathogenic E. coli, the sources of iron used by the pathogens when growing within the host and the specific iron transport systems involved in growth and survival in vivo are not known. Shigella species, the causative agents of dysentery, are closely related to E. coli and share many of the same iron transport systems. However, differences have been noted among this group of pathogens and those differences may relate to differences in sources of iron at various sites within the host or in the environment. Because Shigella spp. have the ability to invade host cells and grow with the cytosol, there may be specific iron transport systems associated with iron acquisition in the intracellular environment. Our first specific aim is to complete the characterization of the Shigella heme transport systems. Many shigellae and pathogenic E. coli, including O157:H7, have specific receptors for heme. Although receptors and other proteins involved in transporting heme across the bacterial cell wall have been identified, other steps in heme acquisition and its use as an iron source are not understood. The second aim is to use genetic and genomic approaches to identify the additional iron uptake systems in these pathogens. We will then apply these data and use the mutants created in these studies to help understand the role of the iron transport systems in growth and survival in vivo and in the environment. Thus our third specific aim is to determine which systems are used under specific environmental conditions and during intracellular growth. Our fourth specific aim is to assess expression of iron transport and other genes during intracellular growth and during infection by using microarray technology.

大多数细菌病原体对铁有绝对的需求。大多数地区铁的可用性低环境的变化导致了高亲和力铁转运系统的进化。虽然各种铁在志贺氏菌和致病性大肠杆菌中已经确定了转运系统。大肠杆菌，铁的来源所使用的病原体在宿主体内生长时，以及参与生长的特定铁转运系统，体内存活率尚不清楚。志贺菌属是痢疾的病原菌，与大肠杆菌有密切的亲缘关系。大肠杆菌和共享许多相同的铁运输系统。然而，人们注意到，一组病原体，这些差异可能与不同地点的铁源差异有关。宿主或环境中。因为志贺氏菌属（Shigella spp.）有能力侵入宿主细胞，在细胞质中，可能存在与细胞内铁获得相关的特异性铁转运系统。环境我们的第一个具体目标是完成志贺氏菌血红素转运系统的表征。许多志贺氏菌和致病性E.包括O157：H7在内的大肠杆菌对血红素具有特异性受体。虽然已经鉴定了参与运输血红素穿过细菌细胞壁的受体和其它蛋白质，血红素获取的其它步骤及其作为铁源的用途还不清楚。第二个目标是使用遗传学和基因组学方法来确定这些病原体中的额外铁吸收系统。我们将然后应用这些数据并使用这些研究中产生的突变体来帮助理解铁的作用，运输系统在体内和环境中的生长和存活。因此，我们的第三个具体目标是确定在特定环境条件下和细胞内生长期间使用哪些系统。我们的第四个具体目标是评估细胞内生长过程中铁转运和其他基因的表达以及在感染过程中。