[
International Worm Meeting,
2021]
Microsporidia are a large and diverse group of fungal-related spore-forming obligate intracellular parasites known to infect hosts in most major animal phyla. Despite the emerging threat that microsporidia have become, few reliable treatment options exist. To address this, we developed a high-throughput drug screening protocol using C. elegans and the microsporidia species Nematocida parisii in order to identify novel chemical inhibitors of microsporidia infection. Using this protocol, we screened through the Spectrum Collection of 2,560 FDA-approved compounds and natural products. We developed a semi-automated method for quantifying progeny number in liquid culture, confirming 11 candidate microsporidia inhibitors. We show that 6 of these compounds, including the known serine protease inhibitor ZPCK, are likely able to prevent microsporidia infection by inhibiting spore firing. We also show that 1 compound, Dexrazoxane, along with the known microsporidia inhibitor Fumagilin, are able to slow infection progression. Given the established role of Dexrazoxane as an iron chelator, it may act by depriving microsporidia of its essential iron resource, consequently putting the brakes on replication within the host. 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 in the future.