Interspecies systems biology links bacterial metabolic pathways to nematode gene expression, behavior, and survival

All animals live in tight association with complex microbial communities, yet studying the effects of individual bacteria remains challenging. Here, we exploit the system of the bacterial feeding nematode Pristionchus pacificus, where specific interactions can be studied in isolation. We sequenced the genomes of 84 Pristionchus-associated bacteria to investigate how differences in bacterial metabolic potential affect nematode traits. Specifically, we identified the Paerucumarin biosynthesis pathway as a strong candidate for nematode survival. Hypothesizing that bacterial production of coumarin derivatives contributed to increased lethality, we demonstrated nematicidal effects of two related compounds using supplementation assays. To explore metabolic interactions at a broader scale, we generated nematode transcriptomes for 38 bacterial diets and constructed a coexpression network that revealed distinct developmental and environmental signatures. Interspecies association studies resulted in a bipartite network with more than 2,800 interactions which may assist future studies to identify metabolites affecting various biological processes.