Medical Research Council Centre for Medical Mycology at the University of Aberdeen, Aberdeen Fungal Group, Institute of Medical Sciences, Foresterhill, Aberdeen, UK.
Trends Microbiol. 2019 Feb;27(2):188-189. doi: 10.1016/j.tim.2018.10.010. Epub 2018 Dec 11.
Pathogens often face zinc restriction due to the action of nutritional immunity - host processes which restrict microbial access to key micronutrients such as zinc and iron. Candida albicans scavenges environmental zinc via two pathways. The plasma membrane transporter Zrt2 is essential for zinc uptake and growth in acidic environments. Neutralisation to pH 7 severely decreases the solubility of ionic Zn; this increase in pH triggers expression and activity of a second zinc scavenging system, the zincophore. This fungus-specific system consists of a secreted zinc-binding protein, Pra1, which captures zinc and returns to the cell via a syntenically expressed receptor, Zrt1. If present in excess, zinc is detoxified via a Zrc1-dependent mechanism. In C. albicans Zrc1 plays an important role in the generation of zincosomes. C. albicans faces both low and high zinc bottlenecks in vivo as Zrt2 and Zrc1 are required for kidney and liver colonisation, respectively, in a murine infection model.
病原体经常面临锌限制，这是由于营养免疫的作用——宿主过程限制了微生物获取关键微量元素（如锌和铁）的途径。白色念珠菌通过两种途径来获取环境中的锌。质膜转运蛋白 Zrt2 是在酸性环境中摄取锌和生长所必需的。中性化至 pH 值 7 会严重降低离子锌的溶解度；这种 pH 值的升高会触发第二种锌摄取系统——锌载体的表达和活性。这个真菌特异性系统由一个分泌的锌结合蛋白 Pra1 组成，它通过一个顺式表达的受体 Zrt1 捕获锌并返回细胞。如果锌过量，锌会通过 Zrc1 依赖的机制解毒。在白色念珠菌中，Zrc1 在锌小体的产生中起着重要作用。白色念珠菌在体内既面临低锌瓶颈，也面临高锌瓶颈，因为在小鼠感染模型中，Zrt2 和 Zrc1 分别是肾脏和肝脏定植所必需的。
