Ahr1 and Tup1 Contribute to the Transcriptional Control of Virulence-Associated Genes in Candida albicans
Ahr1 and Tup1 Contribute to the Transcriptional Control of Virulence-Associated Genes in Candida albicans
复制标题
DOI：
10.1128/mbio.00206-20
复制
发表时间：
2020-03-01
期刊：
影响因子：
6.4
通讯作者：
Martin, Ronny
中科院分区：
文献类型：
--
作者：
Ruben, Sophia;Garbe, Enrico;Martin, Ronny
白色念珠菌在酵母和丝状阶段之间可逆地改变其形态的能力对其毒力至关重要。菌丝的形成与ALS 3和ECE 1基因的上调相关，这两个基因参与致病过程，如入侵、铁获取和宿主细胞损伤。Tup 1及其辅因子Nrg 1被认为是C.白色念珠菌。然而，我们的实验表明，Tup1，而不是Nrg1，是必需的ALS3和ECE1的完全表达。与NRG 1相反，发现TUP 1的过表达既不抑制丝状生长，也不抑制ALS 3和ECE 1的转录。此外，我们确定了转录因子Ahr1是两个基因完全表达所需的。Ahr1的过度活跃版本直接与ALS3和ECE1的启动子结合，即使在没有环境刺激的情况下也能诱导它们的转录。即使在没有关键的菌丝生长调节剂Cph 1和Efg 1的情况下，这种调节也有效，但依赖于Tup 1的存在。总的来说，我们的研究结果表明，Ahr1和Tup1是在不同的C.重要性白色念珠菌是一种主要的人类真菌病原体，并且是全身性念珠菌感染的主要原因。近年来，Als3和Ece1被认为是影响真菌毒力的重要因子。这两个相应基因的转录与菌丝生长密切相关。在这里，我们描述了如何Tup1，通常是一个全球性的基因表达的阻遏物，以及抑制，和转录因子Ahr1有助于充分表达的ALS3和ECE1在白色念珠菌菌丝。这两种调节剂都是这两种基因的高mRNA量所必需的，以确保功能相关的蛋白质合成和定位。这些观察结果确定了一个新的方面的调控复杂的转录控制的毒力相关基因在C。白色念珠菌。
The capacity of Candida albicans to reversibly change its morphology between yeast and filamentous stages is crucial for its virulence. Formation of hyphae correlates with the upregulation of genes ALS3 and ECE1, which are involved in pathogenicity processes such as invasion, iron acquisition, and host cell damage. The global repressor Tup1 and its cofactor Nrg1 are considered to be the main antagonists of hyphal development in C. albicans. However, our experiments revealed that Tup1, but not Nrg1, was required for full expression of ALS3 and ECE1. In contrast to NRG1, overexpression of TUP1 was found to inhibit neither filamentous growth nor transcription of ALS3 and ECE1. In addition, we identified the transcription factor Ahr1 as being required for full expression of both genes. A hyperactive version of Ahr1 bound directly to the promoters of ALS3 and ECE1 and induced their transcription even in the absence of environmental stimuli. This regulation worked even in the absence of the crucial hyphal growth regulators Cph1 and Efg1 but was dependent on the presence of Tup1. Overall, our results show that Ahr1 and Tup1 are key contributors in the complex regulation of virulence-associated genes in the different C. albicans morphologies.IMPORTANCE Candida albicans is a major human fungal pathogen and the leading cause of systemic Candida infections. In recent years, Als3 and Ece1 were identified as important factors for fungal virulence. Transcription of both corresponding genes is closely associated with hyphal growth. Here, we describe how Tup1, normally a global repressor of gene expression as well as of filamentation, and the transcription factor Ahr1 contribute to full expression of ALS3 and ECE1 in C albicans hyphae. Both regulators are required for high mRNA amounts of the two genes to ensure functional relevant protein synthesis and localization. These observations identified a new aspect of regulation in the complex transcriptional control of virulence-associated genes in C. albicans.