MECHANISMS OF MICROBIAL IRON TRANSPORT

微生物铁运输机制

• 批准号: 3124581
• 负责人: THOMAS F. EMERY
• 金额: $ 8.3万
• 依托单位: UTAH STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-09-01 至 1988-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3124581
• 关键词: Desulfovibrio; Escherichia coli; Fusarium; anaerobiosis; analytical method; biological transport; cell free system; chelating agents; esterase; ionophores; iron metabolism; metalloproteins; microorganism growth; microorganism metabolism; ornithine; physical separation; radiotracer; tissue /cell culture

The objective of this research is to understand the detailed molecular mechanisms by which microorganisms sequester iron. Research in this area has previously concentrated on a group of compounds, called siderophores, which chelate ferric ion and transport it into the cells via specific transport systems. However, it is well known that microorganisms can also assimilate the metal from a wide variety of other complexes, such as citric acid and siderophores from non-related organisms. Recent work in our laboratory strongly suggests that often this non-specific uptake involves reduction of the metal to the ferrous state followed by translocation of the metal into the cell with the organic ligand remaining extracellular. Virtually nothing is known about the detailed mechanism of this process. This research would establish the reductive mechanism as general in the microbial kingdom and address questions of the specificity of the system, i.e., can other metals be reduced and is iron octahedrally coordinated to oxygen ligands required. What is the source of electrons for the extracellular reduction? Are membrane-associated ferrireductases involved? Isotopic iron will be complexed to a variety of organic ligands and tested with several unrelated organisms to establish the generality of the process. An appropriate organism, probably E. coli, will be chosen to examine the details. Membrane preparations will be examined for their ability to reduce ferric chelates, and the enzyme responsible will be purified. We will also examine the possibility that fungal esterases, which have been shown to be sensitive to sulfhydryl reagents, act as ferrireductases in the presence of an electron source. There is increasing evidence that iron acquisition plays an important role in the course of bacterial and fungal infections in man, and for this reason research in the role of siderophores in microbial iron transport has become increasingly clinically relevant. However, the finding that microorganisms possess a reductive mechanism of iron transport, which enables them to obtain iron from a host of chelates, puts this area of research in a new light. If chemotherapy based on depriving infecting microorganism of irons is to be truly effective, it will be necessary to understand the mechanism of the reductive transport system also.

这项研究的目的是了解详细的分子 微生物隔离铁的机制。 该领域的研究 以前已经集中在一组称为铁载体的化合物上 哪个螯合铁离子并通过特异性将其运输到细胞中 运输系统。 但是，众所周知，微生物也可以 吸收来自多种其他复合物的金属，例如柠檬酸 来自非相关生物的酸和铁载体。 我们最近的工作 实验室强烈建议这种非特异性吸收涉及 将金属减少到亚铁状态，然后易位 金属带有有机配体保持细胞外的细胞。 实际上，关于此过程的详细机制一无所知。 这项研究将确定还原机制在 微生物王国并解决了系统特异性的问题， 即，可以减少其他金属，并将八面体协调为 需要氧配体。 什么是电子的来源 细胞外还原？ 是与膜相关的屈服酶 涉及？ 同位素铁将复合到各种有机配体 并用几种无关的生物进行测试，以建立 过程。 适当的有机体，可能是大肠杆菌，将被选为 检查细节。 膜准备工作将进行检查 减少螯合铁酸酯的能力，负责的酶将是 纯化。 我们还将研究真菌酯酶的可能性， 已证明对硫酰亚胺试剂敏感，充当 在存在电子源的情况下的铁液酶。 有在增加 铁获取的证据在此过程中起着重要作用 人类的细菌和真菌感染，因此 铁载体在微生物铁运输中的作用越来越多 临床相关。 但是，微生物拥有的发现 铁运输的还原机制，使它们能够获得铁 从许多螯合物中，将这一研究领域置于新的角度。 如果 基于剥夺感染的熨斗的化学疗法将是 真正有效，有必要了解 还还原运输系统。