Candida albicans filamentation, the ability to convert from oval yeast cells to elongated hyphal cells, is a key factor in its pathogenesis. Previous work has shown that the integral membrane protein Dfi1 is required for filamentation in cells grown in contact with a semi-solid surface. Investigations into the downstream targets of the Dfi1 pathway revealed potential links to two transcription factors – Sef1 and Czf1. Sef1 regulates iron uptake and iron utilization genes in low iron conditions, leading us to hypothesize that there exists a link between iron availability and contact-dependent invasive filamentation. Here, we showed that Sef1 was not required for contact dependent filamentation, but it was required for WT expression levels of a number of genes during growth in contact conditions. Czf1 is required for contact-dependent filamentation and for WT levels of expression of several genes. Constitutive expression and activation of either Sef1 or Czf1 individually in a dfi1 null strain resulted in a complete rescue of the dfi1 null filamentation defect. Because Sef1 is normally activated in low-iron environments, we embedded WT and dfi1 null cells in iron-free agar medium supplemented with various concentrations of Ferrous Ammonium Sulfate (FAS). dfi1 null cells embedded in media with a low concentration of iron (20uM FAS) showed increased filamentation in comparison to mutant cells embedded in higher concentrations of iron (50-500uM). WT cells produced filamentous colonies in all concentrations. Together, this data indicates that Dfi1, Czf1, Sef1, and environmental iron regulate C. albicans contact-dependent filamentation.

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铁的可用性与白色念珠菌侵入性丝状形成之间的交叉点

白色念珠菌细丝化，即从椭圆形酵母细胞转化为细长菌丝细胞的能力，是其发病机制的关键因素。以前的工作表明，在与半固体表面接触的细胞中形成丝状体需要完整的膜蛋白 Dfi1。对 Dfi1 通路下游靶点的调查揭示了与两个转录因子——Sef1 和 Czf1 的潜在联系。Sef1 在低铁条件下调节铁摄取和铁利用基因，导致我们假设铁的可用性与依赖接触的侵入性丝状形成之间存在联系。在这里，我们表明 Sef1 不是接触依赖性丝状形成所必需的，但它是接触条件下生长过程中许多基因的 WT 表达水平所必需的。Czf1 是依赖于接触的丝状形成和几种基因的 WT 表达水平所必需的。Sef1 或 Czf1 的组成型表达和激活dfi1空应变导致dfi1空丝缺陷的完全挽救。因为 Sef1 通常在低铁环境中被激活，我们将 WT 和dfi1无效细胞嵌入补充有不同浓度硫酸亚铁铵 (FAS) 的无铁琼脂培养基中。与嵌入高浓度铁 (50-500uM) 的突变细胞相比，嵌入低浓度铁 (20uM FAS) 培养基中的dfi1无效细胞显示出增加的丝化。WT 细胞产生所有浓度的丝状集落。总之，这些数据表明 Dfi1、Czf1、Sef1 和环境铁调节白色念珠菌接触依赖的丝状形成。