The Caenorhabditis elegans microbiome impacts microsporidia infection through nutrient limitation and spore inactivation.

Microsporidia are fungal parasites that can only reproduce inside the cells of a host, and they infect most animal groups, including humans and agriculturally important species. Animals also harbor a microbiome, which can shape resistance to infection, but the mechanisms by which bacteria influence microsporidia infection are poorly understood. To address this, we tested how bacteria associated with the nematode Caenorhabditis elegans affect infection by its natural microsporidian parasite, Nematocida parisii. Here we show that nematodes grown on Chryseobacterium scophthalmum or Sphingobacterium multivorum exhibit increased initial parasite invasion but reduced subsequent growth. Broad profiling of host lipids reveals that these bacteria disrupt levels of unsaturated fatty acids, and adding back one such fatty acid, linoleic acid, restores parasite growth in animals raised on S. multivorum. We also found that Pseudomonas lurida and Pseudomonas mendocina secrete molecules that inactivate N. parisii spores, with P. lurida activity depending on the antimicrobial lipopeptide massetolide. We tested 53 additional Pseudomonas strains, 64% of which significantly reduced N. parisii infection. Our results indicate that bacterial interference with microsporidia is widespread, acting both by reshaping host metabolism and by directly inactivating parasite spores.