Aspergillus fumigatus can cause a variety of lung diseases in immunocompromised patients, including life-threatening invasive aspergillosis. There are only three main classes of antifungal drugs currently used to treat aspergillosis, and antifungal resistance is increasing. Experimental results in fungal biology research are usually obtained as average measurements across whole populations while ignoring what is happening at the single cell level. In this study, we show that conidia with the same genetic background in the same cell population at a similar developmental stage show heterogeneity in their cell wall labeling at the single cell level. We present a rigorous statistical method, newly applied to quantify the level of cell heterogeneity, which allows for direct comparison of the heterogeneity observed between treatments. We show the extent of cell wall labeling heterogeneity in dormant conidia and how the level of heterogeneity changes during germination. The degree of heterogeneity is influenced by deletions of cell wall synthesizing genes and environmental conditions, including medium composition, method of inoculation, age of conidia, and the presence of antifungals. This heterogeneity results in subpopulations of germinating conidia with heterogeneous fitness to the antifungal caspofungin, which targets cell wall synthesis and heterogeneous sensitivity of dormant conidia to phagocytosis by macrophages.

中文翻译：

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烟曲霉中单细胞之间的细胞壁组成异质性导致抗真菌治疗和吞噬作用过程中的异质性行为。

烟曲霉可导致免疫功能低下患者的多种肺部疾病，包括危及生命的侵袭性曲霉病。目前用于治疗曲霉病的抗真菌药物只有三大类，而且抗真菌药物的耐药性正在增加。真菌生物学研究中的实验结果通常是作为整个种群的平均测量值获得的，而忽略了单细胞水平上发生的情况。在这项研究中，我们表明在相同发育阶段的相同细胞群中具有相同遗传背景的分生孢子在单细胞水平上显示出其细胞壁标记的异质性。我们提出了一种严格的统计方法，新应用于量化细胞异质性的水平，它允许直接比较治疗之间观察到的异质性。我们展示了休眠分生孢子中细胞壁标记异质性的程度以及在萌发过程中异质性水平如何变化。异质性的程度受细胞壁合成基因缺失和环境条件的影响，包括培养基组成、接种方法、分生孢子年龄和抗真菌剂的存在。这种异质性导致发芽分生孢子亚群对抗真菌卡泊芬净具有异质性，卡泊芬净靶向细胞壁合成和休眠分生孢子对巨噬细胞吞噬作用的异质敏感性。接种方法、分生孢子年龄和抗真菌剂的存在。这种异质性导致发芽分生孢子亚群对抗真菌卡泊芬净具有异质性，卡泊芬净靶向细胞壁合成和休眠分生孢子对巨噬细胞吞噬作用的异质敏感性。接种方法、分生孢子年龄和抗真菌剂的存在。这种异质性导致发芽分生孢子亚群对抗真菌卡泊芬净具有异质性，卡泊芬净靶向细胞壁合成和休眠分生孢子对巨噬细胞吞噬作用的异质敏感性。