Polyketide synthase-derived sphingolipids determine microbiota-mediated protection against pathogens inC. elegans

Abstract

Protection against pathogens is a major function of the gut microbiota. Although bacterial natural products have emerged as crucial components of host-microbiota interactions, their exact role in microbiota-mediated protection is largely unexplored. We addressed this knowledge gap with the nematode Caenorhabditis elegans and its microbiota isolate Pseudomonas fluorescens MYb115 that is known to protect against Bacillus thuringiensis (Bt) infection. We find that MYb115-mediated protection depends on sphingolipids that are derived from an iterative type I polyketide synthase (PKS), thereby describing a noncanonical pathway of bacterial sphingolipid production. We provide evidence that MYb115-derived sphingolipids affect C. elegans tolerance to Bt infection by altering host sphingolipid metabolism. This work establishes sphingolipids as structural outputs of bacterial PKS and highlights the role of microbiota-derived sphingolipids in host protection against pathogens.

TheCaenorhabditis elegansbacterial microbiome influences microsporidia infection through nutrient limitation and inhibiting parasite invasion

“…Fatty acid supplementation of either palmitic or oleic acid in Drosophila melanogaster resulted in increased proliferation of the microsporidian Tubulinosema ratisbonensis (Franchet et al 2019). Protection against pathogenic bacteria by beneficial bacteria through alterations of host sphingolipid levels has also been observed in C. elegans (Peters et al 2024). We found that the polyunsaturated fat, linoleic acid, can restore N. parisii infectivity in nematodes grown on S. multivorum BIGb0170 and depletion of linoleic acid through the loss of the C. elegans desaturase FAT-2 delays N. parisii sporulation, suggesting an important requirement of polyunsaturated fatty acids for microsporidia infection.…”