Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Via L. Borsari 46, 44121, Ferrara, Italy.
Faculty of Chemistry, University of Wroclaw, ul. F. Joliot-Curie 14, 50-383, Wroclaw, Italy.
Curr Med Chem. 2021;28(35):7312-7338. doi: 10.2174/1389200222666210514012945.
Some transition metals, like manganese, iron, cobalt, nickel, copper and zinc, required for the biosynthesis of metalloenzymes and metalloproteins, are essential micronutrients for the growth and development of pathogenic microorganisms. Among the defenses put in place by the host organism, the so-called "nutritional immunity" consists of reducing the availability of micronutrients and thus "starving" the pathogen. In the case of metals, microorganisms can fight the nutritional immunity in different ways, i.e. by directly recruiting the metal ion or capturing an extracellular metalloprotein or also through the synthesis of specific metallophores which allow importing the metal in the form of a chelate complex. The best known and most studied metallophores are those directed to iron (siderophores), but analogous chelators are also expressed by microorganisms to capture other metals, such as zinc. An efficient zinc recruitment can also be achieved by means of specialized zinc-binding proteins. A deep knowledge of the properties, structure and action mechanisms of extracytoplasmic zinc chelators can be a powerful tool to find out new therapeutic strategies against the antibiotic and/or antifungal resistance. This review aims to collect the knowledge concerning zincophores (small molecules and proteins in charge of zinc acquisition) expressed by bacterial or fungal microorganisms that are pathogenic for the human body.
一些过渡金属，如锰、铁、钴、镍、铜和锌，是生物合成金属酶和金属蛋白所必需的，是致病微生物生长和发育所必需的微量营养素。在宿主生物体所采取的防御措施中，所谓的“营养免疫”包括降低必需微量元素的可用性，从而“饿死”病原体。在金属的情况下，微生物可以通过不同的方式对抗营养免疫，例如直接招募金属离子或捕获细胞外金属蛋白，或者通过合成允许以螯合物形式导入金属的特定金属载体。最著名和研究最多的金属载体是针对铁（铁载体）的，但微生物也表达类似的螯合剂来捕获其他金属，如锌。通过专门的锌结合蛋白也可以有效地招募锌。深入了解细胞外锌螯合剂的特性、结构和作用机制，可以成为寻找针对抗生素和/或抗真菌耐药性的新治疗策略的有力工具。本综述旨在收集有关人体致病的细菌或真菌微生物表达的锌载体（负责锌获取的小分子和蛋白质）的知识。
