Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK.
Institute of Microbiology and Infection, School of Immunity and Infection, University of Birmingham, Birmingham B15 2TT, UK.
Nat Commun. 2016 Oct 31;7:13308. doi: 10.1038/ncomms13308.
Iron is a limiting nutrient in bacterial infection putting it at the centre of an evolutionary arms race between host and pathogen. Gram-negative bacteria utilize TonB-dependent outer membrane receptors to obtain iron during infection. These receptors acquire iron either in concert with soluble iron-scavenging siderophores or through direct interaction and extraction from host proteins. Characterization of these receptors provides invaluable insight into pathogenesis. However, only a subset of virulence-related TonB-dependent receptors have been currently described. Here we report the discovery of FusA, a new class of TonB-dependent receptor, which is utilized by phytopathogenic Pectobacterium spp. to obtain iron from plant ferredoxin. Through the crystal structure of FusA we show that binding of ferredoxin occurs through specialized extracellular loops that form extensive interactions with ferredoxin. The function of FusA and the presence of homologues in clinically important pathogens suggests that small iron-containing proteins represent an iron source for bacterial pathogens.
铁是细菌感染的限制营养素，使其成为宿主和病原体之间进化军备竞赛的核心。革兰氏阴性菌在感染过程中利用 TonB 依赖性外膜受体获取铁。这些受体通过与可溶性铁螯合铁载体协同作用，或通过直接与宿主蛋白相互作用和提取来获取铁。这些受体的表征为发病机制提供了宝贵的见解。然而，目前仅描述了一部分与毒力相关的 TonB 依赖性受体。在这里，我们报告了 FusA 的发现，这是一种新的 TonB 依赖性受体，被植物病原体果胶杆菌属用于从植物铁氧还蛋白中获取铁。通过 FusA 的晶体结构，我们表明铁氧还蛋白的结合是通过形成与铁氧还蛋白广泛相互作用的特殊细胞外环来实现的。FusA 的功能及其在临床上重要病原体中的同源物的存在表明，含铁的小蛋白代表细菌病原体的铁源。
