Department of Cell Biology, New York University School of Medicine, New York, NY, USA.
Department of Biochemistry, University of Utah, Salt Lake City, USA.
Nat Commun. 2023 Nov 23;14(1):7662. doi: 10.1038/s41467-023-43215-0.
Microsporidia are an early-diverging group of fungal pathogens with a wide host range. Several microsporidian species cause opportunistic infections in humans that can be fatal. As obligate intracellular parasites with highly reduced genomes, microsporidia are dependent on host metabolites for successful replication and development. Our knowledge of microsporidian intracellular development remains rudimentary, and our understanding of the intracellular niche occupied by microsporidia has relied on 2D TEM images and light microscopy. Here, we use serial block-face scanning electron microscopy (SBF-SEM) to capture 3D snapshots of the human-infecting species, Encephalitozoon intestinalis, within host cells. We track E. intestinalis development through its life cycle, which allows us to propose a model for how its infection organelle, the polar tube, is assembled de novo in developing spores. 3D reconstructions of parasite-infected cells provide insights into the physical interactions between host cell organelles and parasitophorous vacuoles, which contain the developing parasites. The host cell mitochondrial network is substantially remodeled during E. intestinalis infection, leading to mitochondrial fragmentation. SBF-SEM analysis shows changes in mitochondrial morphology in infected cells, and live-cell imaging provides insights into mitochondrial dynamics during infection. Our data provide insights into parasite development, polar tube assembly, and microsporidia-induced host mitochondria remodeling.
微孢子虫是一类早期分化的真菌病原体，宿主范围广泛。有几种微孢子虫物种会导致人类机会性感染，这些感染可能是致命的。由于微孢子虫是严格的细胞内寄生虫，基因组高度简化，因此它们依赖于宿主代谢物来成功复制和发育。我们对微孢子虫细胞内发育的了解仍然很基础，对微孢子虫所占据的细胞内小生境的理解依赖于 2D TEM 图像和光学显微镜。在这里，我们使用连续块面扫描电子显微镜 (SBF-SEM) 来捕获宿主细胞内感染人类的物种——肠微孢子虫（Encephalitozoon intestinalis）的 3D 快照。我们通过跟踪肠微孢子虫的生命周期来研究其发育，这使我们能够提出一种模型，说明其感染细胞器——极丝，是如何在发育中的孢子中从头组装的。寄生虫感染细胞的 3D 重建提供了对宿主细胞细胞器和包含发育中寄生虫的滋养液泡之间物理相互作用的深入了解。肠微孢子虫感染过程中，宿主细胞的线粒体网络发生了实质性重塑，导致线粒体碎片化。SBF-SEM 分析显示感染细胞中线粒体形态的变化，活细胞成像则提供了感染过程中线粒体动态的见解。我们的数据提供了对寄生虫发育、极丝组装和微孢子虫诱导的宿主线粒体重塑的深入了解。
