Fig. 1: High-throughput screen of 2500 ChemBridge compounds identifies benzenesulfonamides which inhibit N. parisii infection of C. elegans.

A Schematic of N. parisii infection of C. elegans. The process of infection begins when the worms ingest microsporidia spores. These spores then germinate inside of the intestinal lumen of the worm, depositing the sporoplasm inside an intestinal cell. The sporoplasm then differentiates into a meront and differentiates into spores which then exit the worm. B Schematic of assay to identify microsporidia inhibitors. Compounds, microsporidia spores, and E. coli (food source of C. elegans) are incubated together and the C. elegans animals at the earliest larval stage are added. After 5 days of incubation, the worms are stained with rose bengal, imaged using a flatbed scanner, and quantified using image analysis. C Compounds at a final concentration of 60 µM were incubated with N. parisii. L1 stage C. elegans were added one hour later, cultured for five days, and progeny numbers quantified. Points represent mean progeny production of a compound as a percentage of DMSO uninfected controls. Compounds with an activity less than 40% are colored blue, compounds with an activity of at least 40% are colored red, and compound-IDs are shown. Three independent biological replicates were performed for each compound. D Clustered heat map of structural similarity of the 26 compounds with at least 40% activity. The scale indicates compound similarity with 0 (blue) being most similar and 1 (red) being least similar. Compounds tested in subsequent experiments are indicated by the dark blue dots. E Structures of benzenesulfonamides with inhibitory activity against N. parisii.