PT - JOURNAL ARTICLE AU - El Jarkass, Hala Tamim AU - Castelblanco, Stefanie AU - Kaur, Manpreet AU - Wan, Yin Chen AU - Ellis, Abigail E. AU - Sheldon, Ryan D. AU - Lien, Evan C. AU - Burton, Nick O. AU - Wright, Gerard D. AU - Reinke, Aaron W. TI - The <em>Caenorhabditis elegans</em> bacterial microbiome influences microsporidia infection through nutrient limitation and inhibiting parasite invasion AID - 10.1101/2024.06.05.597580 DP - 2024 Jan 01 TA - bioRxiv PG - 2024.06.05.597580 4099 - http://biorxiv.org/content/early/2024/06/05/2024.06.05.597580.short 4100 - http://biorxiv.org/content/early/2024/06/05/2024.06.05.597580.full AB - Microsporidia are eukaryotic obligate intracellular parasites that infect most animals including humans. To understand how the microbiome can impact microsporidia infection, we tested how bacterial isolates that naturally occur with Caenorhabditis elegans influence infection by the microsporidian Nematocida parisii. Nematodes exposed to two of these bacteria, Chryseobacterium scopthalmum and Sphingobacterium multivorum, exhibit reduced pathogen loads. Using untargeted metabolomics, we show that unsaturated fatty acid levels are disrupted by growth on these bacteria and that supplementation with the polyunsaturated fatty acid linoleic acid can restore full parasite growth in animals cultured on S. multivorum. We also found that two isolates, Pseudomonas lurida and Pseudomonas mendocina, secrete molecules that inactivate N. parisii spores. We determined that P. lurida inhibits N. parisii through the production of massetolides. We then measured 53 additional Pseudomonas strains, 64% of which significantly reduced N. parisii infection. A mixture of Pseudomonas species can greatly limit the amount of infection in C. elegans populations over many generations. Our findings suggest that interactions between bacteria and N. parisii are common and that these bacteria both modulate host metabolism and produce compounds that inhibit microsporidia infection.Competing Interest StatementThe authors have declared no competing interest.