Department of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, Kansas 66506, United States.
Venatorx Pharmaceuticals, Inc., 30 Spring Mill Drive, Malvern, Pennsylvania 19355, United States.
Chem Rev. 2021 May 12;121(9):5193-5239. doi: 10.1021/acs.chemrev.0c01005. Epub 2021 Mar 16.
Iron is an indispensable metabolic cofactor in both pro- and eukaryotes, which engenders a natural competition for the metal between bacterial pathogens and their human or animal hosts. Bacteria secrete siderophores that extract Fe from tissues, fluids, cells, and proteins; the ligand gated porins of the Gram-negative bacterial outer membrane actively acquire the resulting ferric siderophores, as well as other iron-containing molecules like heme. Conversely, eukaryotic hosts combat bacterial iron scavenging by sequestering Fe in binding proteins and ferritin. The variety of iron uptake systems in Gram-negative bacterial pathogens illustrates a range of chemical and biochemical mechanisms that facilitate microbial pathogenesis. This document attempts to summarize and understand these processes, to guide discovery of immunological or chemical interventions that may thwart infectious disease.
铁是原核生物和真核生物代谢中不可或缺的辅因子，这导致了细菌病原体与其人类或动物宿主之间对金属的自然竞争。细菌分泌铁载体，从组织、体液、细胞和蛋白质中提取铁；革兰氏阴性细菌外膜的配体门控孔蛋白主动获取由此产生的三价铁载体，以及其他含铁分子，如血红素。相反，真核宿主通过将铁结合在结合蛋白和铁蛋白中来对抗细菌的铁掠夺。革兰氏阴性细菌病原体中的各种铁摄取系统说明了一系列促进微生物发病机制的化学和生化机制。本文试图总结和理解这些过程，以指导发现可能阻止传染病的免疫或化学干预措施。
