Aspergillus fumigatus Survival in Alkaline and Extreme Zinc-Limiting Environments Relies on the Induction of a Zinc Homeostasis System Encoded by the zrfC and aspf2 Genes
Aspergillus fumigatus Survival in Alkaline and Extreme Zinc-Limiting Environments Relies on the Induction of a Zinc Homeostasis System Encoded by the zrfC and aspf2 Genes
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DOI：
10.1128/ec.00348-09
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发表时间：
2010-03-01
期刊：
影响因子：
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通讯作者：
Antonio Calera, Jose
中科院分区：
文献类型：
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作者：
Amich, Jorge;Vicentefranqueira, Rocio;Antonio Calera, Jose
烟曲霉有三个锌转运蛋白编码基因，其表达受pH和环境锌浓度的共同调控。我们之前报道过，烟曲霉的zrfA和zrfB基因转录水平较高，是酸性限锌条件下真菌生长所必需的，而在中性或碱性限锌培养基中则是必不可少的。本文报道了中性或碱性环境下烟曲霉锌吸收系统的转运体是由zrfC编码的。zrfC的转录与相邻的aspf2基因发生差异，该基因编码由烟曲霉分泌的免疫优势抗原。真菌在碱性和极限锌培养基中生长不同程度地需要zrfc和aspf2这两个基因。事实上，这些环境条件诱导由转录调控因子ZafA和PacC介导的两种基因同时转录。ZafA在限锌条件下上调zrfC和aspf2的表达，与环境pH无关，而PacC在酸性生长条件下抑制这些基因的表达。有趣的是，PacC对zrfC-aspf2转录的作用模式与更广泛接受的PacC功能模型相反，根据该模型，在碱性生长条件下，PacC会激活碱性表达基因的转录，而会抑制酸性表达基因的转录。总之，本报告为研究曲霉物种生物学的几个重要方面提供了一个很好的框架，包括酸性pH下PacC对碱性基因的抑制，以及组织pH、宿主组织中金属可用性和真菌毒力之间必须存在的相互关系。
Aspergillus fumigatus has three zinc transporter-encoding genes whose expression is regulated by both pH and the environmental concentration of zinc. We have previously reported that the zrfA and zrfB genes of A. fumigatus are transcribed at higher levels and are required for fungal growth under acidic zinc-limiting conditions whereas they are dispensable for growth in neutral or alkaline zinc-limiting media. Here we report that the transporter of the zinc uptake system that functions in A. fumigatus growing in neutral or alkaline environments is encoded by zrfC. The transcription of zrfC occurs divergently with respect to the adjacent aspf2 gene, which encodes an immunodominant antigen secreted by A. fumigatus. The two genes-zrfC and aspf2-are required to different extents for fungal growth in alkaline and extreme zinc-limiting media. Indeed, these environmental conditions induce the simultaneous transcription of both genes mediated by the transcriptional regulators ZafA and PacC. ZafA upregulates the expression of zrfC and aspf2 under zinc-limiting conditions regardless of the ambient pH, whereas PacC represses the expression of these genes under acidic growth conditions. Interestingly, the mode of action of PacC for zrfC-aspf2 transcription contrasts with the more widely accepted model for PacC function, according to which under alkaline growth conditions PacC would activate the transcription of alkaline-expressed genes but would repress the transcription of acid-expressed genes. In sum, this report provides a good framework for investigating several important aspects of the biology of species of Aspergillus, including the repression of alkaline genes by PacC at acidic pH and the interrelationship that must exist between tissue pH, metal availability in the host tissue, and fungal virulence.