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3D reconstructions of parasite development and the intracellular niche of the microsporidian pathogen Encephalitozoon
Noelle V Antao1, Cherry Lam1, Ari Davydov1
1Department of Cell Biology, New York University School of Medicine, New York, NY, USA.
Abstract:
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.
Insights
This study reveals how microsporidia, fungal pathogens, develop inside host cells using 3D imaging. It details the assembly of the polar tube and host cell mitochondrial remodeling during infection.
Area of Science:
- Mycology
- Cell Biology
- Parasitology
Background:
- Microsporidia are early-diverging fungal pathogens causing opportunistic infections in humans.
- Their intracellular development and niche remain poorly understood, relying on limited 2D imaging techniques.
- As obligate intracellular parasites, they depend on host metabolites for replication.
Purpose of the Study:
- To investigate the intracellular development and host cell interactions of the human-infecting microsporidian species, Encephalitozoon intestinalis.
- To visualize parasite development and organelle assembly in 3D.
- To understand microsporidia-induced host cell remodeling, particularly of mitochondria.
Main Methods:
- Serial block-face scanning electron microscopy (SBF-SEM) for 3D imaging of infected host cells.
- 3D reconstruction of parasite development and host-parasite interactions.
- Live-cell imaging to observe mitochondrial dynamics during infection.
Main Results:
- 3D SBF-SEM provided detailed snapshots of Encephalitozoon intestinalis development within host cells.
- A model for the de novo assembly of the polar tube, the parasite's infection organelle, was proposed.
- Significant remodeling of the host cell mitochondrial network, including fragmentation, was observed during infection.
Conclusions:
- 3D imaging offers novel insights into microsporidian intracellular development and host cell manipulation.
- The study elucidates the process of polar tube assembly and its role in infection.
- Microsporidian infection profoundly impacts host cell mitochondria, affecting their morphology and dynamics.
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