Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
PLoS One. 2012;7(8):e43773. doi: 10.1371/journal.pone.0043773. Epub 2012 Aug 20.
Zinc homeostasis is essential for fungal growth, as this metal is a critical structural component of several proteins, including transcription factors. The fungal pathogen Cryptococcus gattii obtains zinc from the stringent zinc-limiting milieu of the host during the infection process. To characterize the zinc metabolism in C. gattii and its relationship to fungal virulence, the zinc finger protein Zap1 was functionally characterized. The C. gattii ZAP1 gene is an ortholog of the master regulatory genes zafA and ZAP1 that are found in Aspergillus fumigatus and Saccharomyces cerevisiae, respectively. There is some evidence to support an association between Zap1 and zinc metabolism in C. gattii: (i) ZAP1 expression is highly induced during zinc deprivation, (ii) ZAP1 knockouts demonstrate impaired growth in zinc-limiting conditions, (iii) Zap1 regulates the expression of ZIP zinc transporters and distinct zinc-binding proteins and (iv) Zap1 regulates the labile pool of intracellular zinc. In addition, the deletion of ZAP1 reduces C. gattii virulence in a murine model of cryptococcosis infection. Based on these observations, we postulate that proper zinc metabolism plays a crucial role in cryptococcal virulence.
锌稳态对于真菌的生长至关重要，因为这种金属是包括转录因子在内的几种蛋白质的关键结构组成部分。真菌病原体隐球菌属从宿主严格的锌限制环境中获取锌，以在感染过程中获得锌。为了描述隐球菌属中的锌代谢及其与真菌毒力的关系，对锌指蛋白 Zap1 进行了功能表征。C. gattii 的 ZAP1 基因是与其在曲霉菌和酿酒酵母中的主调控基因 zafA 和 ZAP1 同源的基因。有一些证据支持 Zap1 与隐球菌属中的锌代谢之间存在关联：（i）ZAP1 表达在缺锌时高度诱导，（ii）ZAP1 敲除菌株在缺锌条件下表现出生长受损，（iii）Zap1 调节 ZIP 锌转运蛋白和不同的锌结合蛋白的表达，以及（iv）Zap1 调节细胞内锌的可动池。此外，ZAP1 的缺失降低了隐球菌属在隐球菌病感染的小鼠模型中的毒力。基于这些观察结果，我们假设适当的锌代谢在隐球菌属的毒力中起着至关重要的作用。
