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Updated: May 23, 2025
High-throughput Screening and Biosensing with Fluorescent C. elegans Strains
Published on: May 19, 2011
Small-molecule screen in C. elegans identifies benzenesulfonamides as inhibitors of microsporidia spores
Qingyuan Huang1,2, Haiyi Jiang1, Junhong Wei1
1State Key Laboratory of Resource Insects, Chongqing Key Laboratory of Microsporidia Infection and Control, Southwest University, Chongqing, China.
Abstract:
Microsporidia, a large group of fungal-related intracellular parasites, infect several economically significant animals, leading to substantial economic losses. As currently available anti-microsporidia therapies are either ineffective or come with numerous adverse effects, there is a need for alternative microsporidia inhibitors. Here we screen a subset of the ChemBridge DIVERset library, comprising 2500 diverse compounds, using Caenorhabditis elegans infected with its natural microsporidian parasite, Nematocida parisii. By testing these compounds at 60 μM in 96-well assay plates, we identified 26 hits that restored the ability of C. elegans to produce progeny in the presence of N. parisii. We confirmed that out of 20 tested compounds, 18 ChemBridge compounds effectively inhibit N. parisii infection in C. elegans. Of these 18, 10 were benzenesulfonamide derivatives which inhibit microsporidia infection by inactivating spores. We screened an additional 475-compound benzenesulfonamide library, successfully identifying three compounds that are effective at a lower concentration than the initial hits. We further show that one benzenesulfonamide compound displays inhibitory activity against several species of microsporidia, inhibiting infection of species belonging to the Nematocida, Enterocytozoon, and Encephalitozoon genera. Together our results suggest that benzenesulfonamides are a potential scaffold for the development of microsporidia antiseptics.
Insights
Researchers screened compounds to find new microsporidia inhibitors. Benzenesulfonamides showed promise, effectively inhibiting microsporidia infection and inactivating spores in animal models.
Area of Science:
- Mycology
- Parasitology
- Drug Discovery
Background:
- Microsporidia are fungal-related intracellular parasites causing significant economic losses in animals.
- Existing anti-microsporidia therapies are limited by ineffectiveness and adverse effects, necessitating novel treatments.
Purpose of the Study:
- To identify novel inhibitors of microsporidia infection.
- To explore the potential of benzenesulfonamides as a scaffold for new anti-microsporidia agents.
Main Methods:
- Screening of the ChemBridge DIVERset library against *Caenorhabditis elegans* infected with *Nematocida parisii*.
- Confirmation of inhibitory activity of identified compounds against *N. parisii*.
- Further screening of a benzenesulfonamide library and evaluation of broad-spectrum activity.
Main Results:
- 26 compounds restored progeny production in infected *C. elegans*.
- 18 of 20 tested compounds inhibited *N. parisii* infection.
- 10 benzenesulfonamide derivatives were identified, with some inactivating spores and showing broad-spectrum activity against multiple microsporidia genera.
Conclusions:
- Benzenesulfonamides are effective inhibitors of microsporidia infection.
- This class of compounds shows potential as a scaffold for developing new microsporidia antiseptics.
