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Lookup NU author(s): Dr Johan PanekORCiD, Dr Kacper Sendra, Professor Viktor KorolchukORCiD, Emeritus Professor Robert HirtORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Intracellular pathogens such as Microsporidia can interfere with host proteostasis pathways, including autophagy. While the manipulation of host autophagy has been demonstrated in a nematode-infecting species, and autophagic activity was also observed in tardigrade midgut infections, it remains unclear whether this strategy extends to mammalian-infecting Microsporidia. Here, we investigated interactions between host autophagy and two human-pathogenic Microsporidian species representing distinct evolutionary lineages. Using immunochemistry, super-resolution fluorescence microscopy, and modulation of autophagy via siRNA silencing and chemical agents, we show that Encephalitozoon cuniculi is tagged by early autophagy markers (ubiquitin and p62) but escapes clearance via autolysosomes. Instead of restricting the parasite, autophagy induction significantly enhances Microsporidia proliferation in two mammalian cell models. Conversely, autophagy suppression—via siRNA or treatment with microbiota-derived metabolites important for gut epithelial homeostasis—reduces parasite growth. These findings demonstrate that the ability to evade and exploit host autophagy is not restricted to nematode-infecting species but is conserved across diverse Microsporidia infecting mammals. Together with adaptations such as NTT nucleotide transporters, the hijacking of autophagy emerges as a core strategy supporting the obligate intracellular lifestyle of these pathogens.
Author(s): Panek J, Carriere E, Saleh MB, Sendra K, Kosta G, Korolchuk VI, Hirt RP
Publication type: Article
Publication status: Published
Journal: mBio
Year: 2025
Volume: 16
Online publication date: 30/05/2025
Acceptance date: 05/05/2025
Date deposited: 13/06/2025
ISSN (print): 2161-2129
ISSN (electronic): 2150-7511
Publisher: American Society of Microbiology
URL: https://doi.org/10.1128/mbio.01049-25
DOI: 10.1128/mbio.01049-25
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