Candida albicans is a major fungal pathogen that can utilise hemin and haemoglobin as iron sources in the iron‐scarce host environment. While C. albicans is a heme prototroph, we show here that it can also efficiently utilise external heme as a cellular heme source. Using genetically encoded ratiometric fluorescent heme sensors, we show that heme extracted from haemoglobin and free hemin enter the cells with different kinetics. Heme supplied as haemoglobin is taken up via the Common in Fungal Extracellular Membrane (CFEM) hemophore cascade, and reaches the cytoplasm over several hours, whereas entry of free hemin via CFEM‐dependent and independent pathways is much faster, less than an hour. To prevent an influx of extracellular heme from reaching toxic levels in the cytoplasm, the cells deploy Hmx1, a heme oxygenase. Hmx1 was previously suggested to be involved in utilisation of haemoglobin and hemin as iron sources, but we find that it is primarily required to prevent heme toxicity. Taken together, the combination of novel heme sensors with genetic analysis revealed new details of the fungal mechanisms of heme import and homeostasis, necessary to balance the uses of heme as essential cofactor and potential iron source against its toxicity.

中文翻译：

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使用基因编码的血红素传感器探测白色念珠菌中血红素摄取和体内平衡的机制

白色念珠菌是一种主要的真菌病原体，可在缺铁宿主环境中利用血红素和血红蛋白作为铁源。而白色念珠菌是一种血红素原养型，我们在这里展示它还可以有效地利用外部血红素作为细胞血红素来源。使用基因编码的比率荧光血红素传感器，我们表明从血红蛋白和游离血红素中提取的血红素以不同的动力学进入细胞。以血红蛋白形式提供的血红素通过真菌细胞外膜 (CFEM) 血细胞级联吸收，并在几个小时内到达细胞质，而通过 CFEM 依赖和独立途径进入游离血红素要快得多，不到一个小时。为了防止细胞外血红素的流入达到细胞质中的毒性水平，细胞部署了 Hmx1，一种血红素加氧酶。Hmx1 以前被认为参与利用血红蛋白和血红素作为铁源，但我们发现它主要是防止血红素毒性所必需的。