High-throughput small molecule screen identifies inhibitors of microsporidia invasion and proliferation in C. elegans
High-throughput small molecule screen identifies inhibitors of microsporidia invasion and proliferation in C. elegans
Abstract Microsporidia are a diverse group of fungal-related obligate intracellular parasites that infect most animal phyla. Despite the emerging threat that microsporidia have become to humans and agricultural animals, few reliable treatment options exist. To identify novel chemical inhibitors of microsporidia infection, we developed a high-throughput screening method using Caenorhabditis elegans and the microsporidia species Nematocida parisii. We screened the Spectrum Collection of 2,560 FDA-approved compounds and natural products to identify compounds that prevent C. elegans progeny inhibition caused by N. parisii infection. We developed a semi-automated method for quantifying C. elegans progeny number in liquid culture, confirming 11 candidate microsporidia inhibitors. We show that five compounds prevent microsporidia infection by inhibiting spore firing, and demonstrate that one compound, dexrazoxane, slows infection progression. We also show that these compounds have activity against several other microsporidia species, including those which infect humans. Together, our results demonstrate the effectiveness of C. elegans as a model host for drug discovery against intracellular pathogens and provide a scalable high-throughput system for the identification and characterization of additional microsporidia inhibitors.
Knox Jessica、Bhabha Gira、Zhao Winnie、El Alaoui Hicham、Murareanu Brandon M.、Ekiert Damian C.、Dubuffet Aurore、Roy Peter J.、Reinke Aaron W.、Antao Noelle V.
Department of Molecular Genetics, University of Toronto||The Donnelly Centre for Cellular and Biomolecular Research, University of TorontoDepartment of Cell Biology, New York University School of MedicineDepartment of Molecular Genetics, University of TorontoUniversit¨| Clermont Auvergne, CNRS, Laboratoire Microorganismes: G¨|nome et EnvironnementDepartment of Molecular Genetics, University of TorontoDepartment of Cell Biology, New York University School of Medicine||Department of Microbiology, New York University School of MedicineUniversit¨| Clermont Auvergne, CNRS, Laboratoire Microorganismes: G¨|nome et EnvironnementDepartment of Molecular Genetics, University of Toronto||The Donnelly Centre for Cellular and Biomolecular Research, University of TorontoDepartment of Molecular Genetics, University of TorontoDepartment of Cell Biology, New York University School of Medicine
医学研究方法微生物学分子生物学
Knox Jessica,Bhabha Gira,Zhao Winnie,El Alaoui Hicham,Murareanu Brandon M.,Ekiert Damian C.,Dubuffet Aurore,Roy Peter J.,Reinke Aaron W.,Antao Noelle V..High-throughput small molecule screen identifies inhibitors of microsporidia invasion and proliferation in C. elegans[EB/OL].(2025-03-28)[2025-05-10].https://www.biorxiv.org/content/10.1101/2021.09.06.459184.点此复制
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