Related Experiment Video
Updated: Aug 27, 2025
A High-throughput, High-content, Liquid-based C. elegans Pathosystem
Published on: July 1, 2018
High-throughput small molecule screen identifies inhibitors of microsporidia invasion and proliferation in C. elegans
Brandon M Murareanu1, Noelle V Antao2, Winnie Zhao1
1Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
Abstract:
Microsporidia are a diverse group of fungal-related obligate intracellular parasites that infect most animal phyla. Despite the emerging threat that microsporidia represent to humans and agricultural animals, few reliable treatment options exist. Here, we develop a high-throughput screening method for the identification of chemical inhibitors of microsporidia infection, using liquid cultures of Caenorhabditis elegans infected with the microsporidia species Nematocida parisii. We screen a collection of 2560 FDA-approved compounds and natural products, and identify 11 candidate microsporidia inhibitors. Five compounds prevent microsporidia infection by inhibiting spore firing, whereas one compound, dexrazoxane, slows infection progression. The compounds have in vitro activity against several other microsporidia species, including those known to infect humans. Together, our results highlight 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 microsporidia inhibitors.
Insights
Researchers screened FDA-approved compounds to find treatments for microsporidia, a fungal parasite. They identified 11 potential inhibitors, including dexrazoxane, offering new hope for treating infections in humans and animals.
Area of Science:
- Mycology
- Parasitology
- Drug Discovery
Background:
- Microsporidia are fungal-related obligate intracellular parasites infecting diverse animal phyla.
- Emerging microsporidia threats to humans and agriculture lack effective treatments.
Purpose of the Study:
- To develop a high-throughput screening method for identifying microsporidia inhibitors.
- To discover chemical compounds effective against microsporidia infections.
Main Methods:
- Utilized liquid cultures of Caenorhabditis elegans infected with Nematocida parisii.
- Screened a library of 2560 FDA-approved compounds and natural products.
- Assessed compound activity against spore firing and infection progression.
Main Results:
- Identified 11 candidate microsporidia inhibitors from the screened compounds.
- Five compounds inhibited microsporidia spore firing; dexrazoxane slowed infection.
- Tested compounds showed in vitro activity against human-pathogenic microsporidia species.
Conclusions:
- Caenorhabditis elegans is an effective model host for discovering drugs against intracellular pathogens.
- A scalable high-throughput system was established for identifying and characterizing microsporidia inhibitors.
- Identified compounds provide a starting point for developing novel microsporidia treatments.
