Department of Food and Animal Biotechnology, Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, South Korea.
Department of Agricultural Biotechnology, Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, South Korea.
Appl Environ Microbiol. 2019 Apr 18;85(9). doi: 10.1128/AEM.03026-18. Print 2019 May 1.
Iron is one of most abundant environmental metal ions but is highly limited in organisms. It is an important metal ion as it facilitates various biological processes, including catalysis of metabolic enzymes and DNA biogenesis. In bacteria, the ferric uptake regulator (Fur) protein controls iron uptake by regulating genes coding for iron transporters in response to iron concentration. This iron response is ascribed to Fur's intrinsic affinity for iron because its binding to iron dictates its regulatory function. However, we now report that the pathogen achieves a proper response of Fur to changes in environmental iron concentrations via EIIA (a nitrogen metabolic phosphotransferase system component). We establish that EIIA increases expression of iron transporter-coding genes under low-iron conditions (i.e., nanomolar ranges) in a Fur-dependent manner, which promotes growth under such conditions. EIIA directly hampers Fur binding to DNA, thereby inducing expression of those genes. This regulation allows to express Fur-regulated genes under low-iron conditions. Our findings reveal a potentially widespread control mechanism of bacterial iron uptake systems operating in response to iron availability. Iron is a fundamental metal ion for living organisms as it facilitates various biological processes. The ferric uptake regulator (Fur) protein controls iron homeostasis in various bacterial species. It is believed that Fur's iron-dependent regulatory action is sufficient for it to function as an iron sensor. However, we now establish that the bacterial pathogen enables Fur to properly reflect changes in surrounding iron availability by fine-tuning its responsiveness to iron. This process requires a protein that hampers Fur DNA binding at low iron concentrations. In this way, broadens the range of iron concentrations that Fur responds to. Our findings reveal a potentially widespread control mechanism of bacterial iron homeostasis.
铁是环境中最丰富的金属离子之一，但在生物体中高度受限。它是一种重要的金属离子，因为它促进了各种生物过程，包括代谢酶的催化和 DNA 的生物发生。在细菌中，铁摄取调节蛋白（Fur）蛋白通过调节编码铁转运蛋白的基因来控制铁摄取，以响应铁浓度。这种铁反应归因于 Fur 对铁的固有亲和力，因为它与铁的结合决定了其调节功能。然而，我们现在报告称，病原体 通过 EIIA（氮代谢磷酸转移酶系统成分）实现 Fur 对环境铁浓度变化的适当反应。我们确定 EIIA 以 Fur 依赖的方式在低铁条件（即纳摩尔范围）下增加铁转运蛋白编码基因的表达，从而促进 在这种条件下的生长。EIIA 直接阻碍 Fur 与 DNA 的结合，从而诱导这些基因的表达。这种调节允许 在低铁条件下表达 Fur 调节的基因。我们的发现揭示了一种潜在的广泛控制机制，该机制可操作以响应铁的可用性来调节细菌铁摄取系统。铁是生物体的基本金属离子，因为它促进了各种生物过程。铁摄取调节蛋白（Fur）蛋白控制各种细菌物种的铁动态平衡。人们认为 Fur 的铁依赖性调节作用足以使其作为铁传感器发挥作用。然而，我们现在确定细菌病原体 通过微调其对铁的响应能力，使 Fur 能够正确反映周围铁可用性的变化。这个过程需要一种蛋白质，它在低铁浓度下阻碍 Fur DNA 结合。通过这种方式， 扩大了 Fur 响应的铁浓度范围。我们的发现揭示了一种潜在的广泛控制机制，该机制可操作以响应铁的可用性来调节细菌铁动态平衡。
