The human-pathogenic fungus Aspergillus fumigatus is a ubiquitous saprophyte that causes fatal lung infections in immunocompromised individuals. Following inhalation, conidia are ingested by innate immune cells and can arrest phagolysosome maturation. How this virulence trait could have been selected for in natural environments is unknown. Here, we found that surface exposure of the green pigment 1,8-dihydroxynaphthalene-(DHN)-melanin can protect conidia from phagocytic uptake and intracellular killing by the fungivorous amoeba Protostelium aurantium and delays its exocytosis from the nonfungivorous species Dictyostelium discoideum. To elucidate the antiphagocytic properties of the surface pigment, we followed the antagonistic interactions of A. fumigatus conidia with the amoebae in real time. For both amoebae, conidia covered with DHN-melanin were internalized at far lower rates than were seen with conidia lacking the pigment, despite high rates of initial attachment to nonkilling D. discoideum. When ingested by D. discoideum, the formation of nascent phagosomes was followed by transient acidification of phagolysosomes, their subsequent neutralization, and, finally, exocytosis of the conidia. While the cycle was completed in less than 1 h for unpigmented conidia, the process was significantly prolonged for conidia covered with DHN-melanin, leading to an extended intracellular residence time. At later stages of this cellular infection, pigmented conidia induced enhanced damage to phagolysosomes and infected amoebae failed to recruit the ESCRT (endosomal sorting complex required for transport) membrane repair machinery or the canonical autophagy pathway to defend against the pathogen, thus promoting prolonged intracellular persistence in the host cell and the establishment of a germination niche in this environmental phagocyte.

中文翻译：

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人类致病真菌烟曲霉的分生孢子黑色素破坏阿米巴细胞的自主防御。


人类致病真菌烟曲霉是一种普遍存在的腐生菌，可导致免疫功能低下个体致命的肺部感染。吸入后，分生孢子被先天免疫细胞摄入，并可以阻止吞噬溶酶体成熟。在自然环境中如何选择这种毒力特征尚不清楚。在这里，我们发现绿色色素1,8-二羟基萘-(DHN)-黑色素的表面暴露可以保护分生孢子免受食真菌阿米巴原网柄菌的吞噬和细胞内杀伤，并延迟其从非食真菌物种盘基网柄菌的胞吐作用。为了阐明表面色素的抗吞噬特性，我们实时跟踪了烟曲霉分生孢子与阿米巴原虫的拮抗相互作用。对于两种变形虫来说，覆盖有 DHN 黑色素的分生孢子的内化速​​度远低于缺乏色素的分生孢子，尽管最初与非杀伤性盘状D. discoideum的附着率很高。当被盘状D. discoideum摄入时，新生吞噬体形成，随后吞噬溶酶体短暂酸化，随后中和，最后进行分生孢子的胞吐作用。对于未着色的分生孢子来说，该循环在不到 1 小时内完成，而对于被 DHN-黑色素覆盖的分生孢子来说，该过程显着延长，从而导致细胞内停留时间延长。 在这种细胞感染的后期阶段，有色分生孢子诱导了对吞噬溶酶体的增强损伤，并且受感染的变形虫无法招募ESCRT（运输所需的内体分选复合物）膜修复机制或经典自噬途径来防御病原体，从而促进在宿主细胞中延长细胞内持久性并在该环境吞噬细胞中建立萌发生态位。