School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
Mol Microbiol. 2013 Oct;90(1):36-53. doi: 10.1111/mmi.12345. Epub 2013 Aug 15.
Efg1 (a member of the APSES family) is an important regulator of hyphal growth and of the white-to-opaque transition in Candida albicans and very closely related species. We show that in Candida parapsilosis Efg1 is a major regulator of a different morphological switch at the colony level, from a concentric to smooth morphology. The rate of switching is at least 20-fold increased in an efg1 knockout relative to wild type. Efg1 deletion strains also have reduced biofilm formation, attenuated virulence in an insect model, and increased sensitivity to SDS and caspofungin. Biofilm reduction is more dramatic in in vitro than in in vivo models. An Efg1 paralogue (Efh1) is restricted to Candida species, and does not regulate concentric-smooth phenotype switching, biofilm formation or stress response. We used ChIP-seq to identify the Efg1 regulon. A total of 931 promoter regions bound by Efg1 are highly enriched for transcription factors and regulatory proteins. Efg1 also binds to its own promoter, and negatively regulates its expression. Efg1 targets are enriched in binding sites for 93 additional transcription factors, including Ndt80. Our analysis suggests that Efg1 has an ancient role as regulator of development in fungi, and is central to several regulatory networks.
Efg1（APSES 家族的一员）是白色至不透明转变的丝状生长和重要调节因子在白色念珠菌及其密切相关的物种中。我们表明，在近平滑念珠菌中，Efg1 是菌落水平上另一种不同形态转换的主要调节因子，从同心形态到光滑形态。在 efg1 敲除株中，转换率至少增加了 20 倍。与野生型相比，efg1 缺失菌株的生物膜形成也减少，在昆虫模型中的毒力降低，对 SDS 和卡泊芬净的敏感性增加。生物膜减少在体外模型中比体内模型更为显著。Efg1 同源物（Efh1）仅限于念珠菌属，不调节同心-光滑表型转换、生物膜形成或应激反应。我们使用 ChIP-seq 来鉴定 Efg1 的调控组。共有 931 个启动子区域被 Efg1 结合，这些区域高度富集转录因子和调节蛋白。Efg1 还结合其自身的启动子，并负调控其表达。Efg1 的靶标富含 93 个额外转录因子的结合位点，包括 Ndt80。我们的分析表明，Efg1 在真菌发育中作为调节因子具有古老的作用，是几个调节网络的核心。
