Department of Chemistry, Indiana University, Bloomington, IN 47405-7102, USA.
Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, IN 47405-7102, USA.
Chembiochem. 2020 Jul 16;21(14):1955-1967. doi: 10.1002/cbic.201900778. Epub 2020 Apr 14.
Sequestration of the essential nutrient iron from bacterial invaders that colonize the vertebrate host is a central feature of nutritional immunity and the "fight over transition metals" at the host-pathogen interface. The iron quota for many bacterial pathogens is large, as iron enzymes often make up a significant share of the metalloproteome. Iron enzymes play critical roles in respiration, energy metabolism, and other cellular processes by catalyzing a wide range of oxidation-reduction, electron transfer, and oxygen activation reactions. In this Concept article, we discuss recent insights into the diverse ways that bacterial pathogens acquire this essential nutrient, beyond the well-characterized tris-catecholate Fe complexes, in competition and cooperation with significant host efforts to cripple these processes. We also discuss pathogen strategies to adapt their metabolism to less-than-optimal iron concentrations, and briefly speculate on what might be an integrated adaptive response to the concurrent limitation of both iron and zinc in the infected host.
从定殖于脊椎动物宿主的细菌病原体中隔离必需营养铁是营养免疫的核心特征,也是宿主-病原体界面上“过渡金属之争”。许多细菌病原体的铁配额很大,因为铁酶通常构成金属蛋白酶组的重要组成部分。铁酶通过催化广泛的氧化还原、电子转移和氧激活反应,在呼吸、能量代谢和其他细胞过程中发挥关键作用。在这篇概念文章中,我们讨论了最近对细菌病原体获取这种必需营养物质的多种方式的深入了解,这些方式超出了众所周知的三儿茶酚 Fe 配合物,包括与宿主在削弱这些过程方面的重要努力相竞争和合作。我们还讨论了病原体适应其代谢以适应低于最佳铁浓度的策略,并简要推测了感染宿主同时限制铁和锌时可能会产生什么样的综合适应反应。