RT Journal Article SR Electronic T1 The Caenorhabditis elegans bacterial microbiome influences microsporidia infection through nutrient limitation and inhibiting parasite invasion JF bioRxiv FD Cold Spring Harbor Laboratory SP 2024.06.05.597580 DO 10.1101/2024.06.05.597580 A1 El Jarkass, Hala Tamim A1 Castelblanco, Stefanie A1 Kaur, Manpreet A1 Wan, Yin Chen A1 Ellis, Abigail E. A1 Sheldon, Ryan D. A1 Lien, Evan C. A1 Burton, Nick O. A1 Wright, Gerard D. A1 Reinke, Aaron W. YR 2024 UL http://biorxiv.org/content/early/2024/06/05/2024.06.05.597580.abstract 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.