Programa de Pós-Graduação em Biologia Celular e Molecular, Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Laboratório Nacional de Computação Científica, LNCC, Petrópolis, Rio de Janeiro, Brazil.
Genomics. 2021 Mar;113(2):805-814. doi: 10.1016/j.ygeno.2021.01.023. Epub 2021 Jan 30.
Cryptococcus gattii is one of the causes of cryptococcosis, a life-threatening disease generally characterized by pneumonia and/or meningitis. Zinc is an essential element for life, being required for the activity of many proteins with catalytic and structural roles. Here, we characterize ZRG1 (zinc-related gene 1), which codes a product involved in zinc metabolism. Transcriptional profiling revealed that zinc availability regulated the expression of ZRG1, and its null mutants demonstrated impaired growth in zinc- and nitrogen-limiting conditions. Moreover, zrg1 strains displayed alterations in the expression of the zinc homeostasis-related genes ZAP1 and ZIP1. Notably, cryptococcal cells lacking Zrg1 displayed upregulation of autophagy-like phenotypes. Despite no differences were detected in the classical virulence-associated traits; cryptococcal cells lacking ZRG1 displayed decreased capacity for survival inside macrophages and attenuated virulence in an invertebrate model. Together, these results indicate that ZRG1 plays an important role in proper zinc metabolism, and is necessary for cryptococcal fitness and virulence.
新生隐球菌是隐球菌病的病因之一，这种危及生命的疾病通常表现为肺炎和/或脑膜炎。锌是生命所必需的元素，是许多具有催化和结构作用的蛋白质活性所必需的。在这里，我们对编码参与锌代谢的产物的 ZRG1（锌相关基因 1）进行了表征。转录谱分析显示，锌的可用性调节了 ZRG1 的表达，其缺失突变体在缺锌和氮限制条件下的生长受到损害。此外，zrg1 菌株中与锌稳态相关的基因 ZAP1 和 ZIP1 的表达发生改变。值得注意的是，缺乏 Zrg1 的新生隐球菌细胞表现出自噬样表型的上调。尽管在经典的与毒力相关的特征中没有检测到差异；缺乏 ZRG1 的新生隐球菌细胞在巨噬细胞内的存活能力下降，在无脊椎动物模型中的毒力减弱。总之，这些结果表明 ZRG1 在适当的锌代谢中发挥重要作用，是新生隐球菌适应和毒力所必需的。
