3D reconstructions of parasite development and the intracellular niche of the microsporidian pathogen Encephalitozoon intestinalis.
Noelle V AntaoCherry LamAri DavydovMargot RiggiJoseph SallChristopher PetzoldFeng-Xia LiangJanet H IwasaDamian C EkiertGira BhabhaPublished in: Nature communications (2023)
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.
Keyphrases
- induced apoptosis
- oxidative stress
- life cycle
- cell cycle arrest
- plasmodium falciparum
- high resolution
- reactive oxygen species
- electron microscopy
- healthcare
- single cell
- computed tomography
- cell proliferation
- cell death
- optical coherence tomography
- machine learning
- stem cells
- high throughput
- bone marrow
- mesenchymal stem cells
- big data
- drug induced
- genetic diversity
- high speed
- stress induced